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Charles F. levinthal hofstra University

Eighth Edition

Drugs, Behavior, and Modern society

Editor in Chief: Ashley Dodge Acquisitions Editor: Susan Hartman Director of Marketing: Brandy Dawson Executive Marketing Manager: Kelly May Marketing Coordinator: Courtney Stewart Managing Editor: Denise Forlow Program Manager: Reena Dalal Senior Operations Supervisor: Mary Fischer Operations Specialist: Diane Peirano Art Director: Jayne Conte Cover Designer: Bruce Kenselaar

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Library of Congress Cataloging-in-Publication Data

Levinthal, Charles F. Drugs, behavior, and modern society / Charles F. Levinthal, Hofstra University. — Eighth edition. pages cm Includes index. ISBN-13: 978-0-205-95933-4 ISBN-10: 0-205-95933-4 1 . D r u g s . 2 . D r u g a b u s e . 3 . D r u g s — P h y s i o l o g i c a l e f f e c t . 4 . P s y c h o t r o p i c drugs. 5. Psychopharmacology. I. Title. HV5801.L49 2014 362.29—dc23

2013013402

10 9 8 7 6 5 4 3 2 1

ISBN-10: 0-205-95933-4 ISBN-13: 978-0-205-95933-4

For my grandsons

aaron Matthew levinthal and

Michael samuel levinthal

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Brief Contents ■ v

BriEf ContEnts

Part onE drugs in society/drugs in our Lives 1

Chapter 1 Drugs and Behavior today 1

Chapter 2 Drug-taking Behavior: personal and social issues 28

Chapter 3 how Drugs Work in the Body and on the Mind 60

Part two Legally restricted drugs in our society 89

Chapter 4 the Major stimulants: Cocaine and amphetamines 89

Chapter 5 Opioids: Opium, heroin, and Opioid pain Medications 118

Chapter 6 lsD and Other hallucinogens 143

Chapter 7 Marijuana 167

Part thrEE Legal drugs in our society 191

Chapter 8 alcohol: social Beverage/social Drug 191

Chapter 9 Chronic alcohol abuse and alcoholism 220

Chapter 10 nicotine and tobacco Use 248

Chapter 11 Caffeine 275

Part four Enhancers and depressants 293

Chapter 12 performance-enhancing Drugs and Drug testing in sports 293

Chapter 13 Depressants and inhalants 315

Part fivE Medicinal drugs 339

Chapter 14 prescription Drugs, Over-the-Counter Drugs, and Dietary

supplements 339

Chapter 15 Drugs for treating schizophrenia and Mood Disorders 362

Part six Prevention and treatment 379

Chapter 16 substance-abuse prevention 379

Chapter 17 substance-abuse treatment: strategies for Change 407

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Contents ■ vii

ContEnts

preface xix

Part onE drugs in society/ drugs in our Lives 1

Chapter 1

Drugs and Behavior today 1

By the Numbers . . . 2 Social Messages About Drug Use 3 Two Ways of Looking at Drugs and Behavior 4

A Matter of Definition: What Is a Drug? 5

■ h E a L t h L i n E : Defining Drugs: Olive Oil, Curry Powder, and a Little Grapefruit? 6 Instrumental Drug Use/Recreational Drug Use 6 Drug Misuse or Drug Abuse? 7

■ d r u g s . . . i n f o C u s : Drug Abuse and the College Student: An Assessment Tool 8

Drugs in Early Times 9 Drugs in the Nineteenth Century 10 Drugs and Behavior in the Twentieth Century 11

Drugs and Behavior from 1945 to 1960 12 Drugs and Behavior after 1960 12

■ Q u i C k C o n C E P t C h E C k 1 . 1 : Understanding the History of Drugs and Behavior 13

Present-Day Attitudes toward Drugs 14 Patterns of Drug Use in the United States 14

Illicit Drug Use among High School Seniors 15 Illicit Drug Use among Eighth Graders and Tenth

Graders 16 Illicit Drug Use among College Students 16 Alcohol Use among High School and College Students 16 Tobacco Use among High School and College Students 17 Drug Use and Drug Perceptions 17 Illicit Drug Use among Adults Aged Twenty-Six and

Older 18 Making the Decision to Use Drugs 19

■ Q u i C k C o n C E P t C h E C k 1 . 2 : Understanding Present-Day Drug Use in the United States 19

Specific Risk Factors 19 Specific Protective Factors 21

Present-day Concerns 21 Club Drugs 21 Nonmedical Use of Prescription Pain Relievers 21

■ d r u g s . . . i n f o C u s : Facts about Club Drugs 22 Nonmedical Use of Prescription Stimulant Medications 23 Nonmedical Use of Over-the-Counter Cough-and-Cold

Medications 23 Why Drugs? 23

■ P o r t r a i t : From Oxy to Heroin— The Life and Death of Erik 24

Summary 24 / Key Terms 25 / Endnotes 26

Chapter 2

Drug-taking Behavior: personal and social issues 28

By the Numbers . . . 29 Drug Toxicity 30

■ d r u g s . . . i n f o C u s : Acute Toxicity in the News: Drug-Related Deaths 32

■ Q u i C k C o n C E P t C h E C k 2 . 1 : Understanding Dose-Response Curves 33

The DAWN Reports 33 Emergencies Related to Illicit Drugs 34 Drug-Related Deaths 34 Judging Drug Toxicity from Drug-Related Deaths 35 Demographics and Trends 35

From Acute Toxicity to Chronic Toxicity 36 Behavioral Tolerance and Drug Overdose 37

■ Q u i C k C o n C E P t C h E C k 2 . 2 : Understanding Behavioral Tolerance through Conditioning 38

Physical and Psychological Dependence 39 Physical Dependence 39 Psychological Dependence 39

Diagnosing Drug-Related Problems: The Health Professional’s Perspective 41

viii ■ Contents

Special Circumstances in Drug Abuse 43 Drug Abuse in Pregnancy 43 Drug Abuse and HIV Infection 43

■ h E a L t h L i n E : Effects of Psychoactive Drugs on Pregnant Women and Newborns 44

Drugs, Violence, and Crime 45 Pharmacological Violence 45 Economically Compulsive Violence 46 Systemic Violence 47

Governmental Policy, Regulation, and Laws 48 Efforts to Regulate Drugs, 1900–1970 48 Rethinking the Approach toward Drug Regulation,

1970–Present 49 Drug Law Enforcement and Global Politics 50

■ P o r t r a i t : Pablo Escobar—Formerly Known as the Colombian King of Cocaine 51

■ h E a L t h L i n E : Harm Reduction as a National Drug-Abuse Policy 53

Summary 54 / Key Terms 55 / Endnotes 55

■ P o i n t / C o u n t E r P o i n t i : Should We Legalize Drugs in General? 58

Chapter 3

how Drugs Work in the Body and on the Mind 60

By the Numbers . . . 61 How Drugs Enter the Body 61

Oral Administration 61 Injection 62 Inhalation 63 Absorption through the Skin or Membranes 63

How Drugs Exit the Body 64

■ d r u g s . . . i n f o C u s : Ways to Take Drugs: Routes of Administration 65

Factors Determining the Behavioral Impact of Drugs 66 Timing 66 Drug Interactions 67 Cross-Tolerance and Cross-Dependence 67

■ Q u i C k C o n C E P t C h E C k 3 . 1 : Understanding Drug Interactions 67

■ h E a L t h a L E r t : Adverse Effects of Drug– Drug and Food–Drug Combinations 68 Individual Differences 69

Introducing the Nervous System 69 The Peripheral Nervous System 70 Sympathetic and Parasympathetic Responses 70 The Central Nervous System 71

Understanding the Brain 72 The Hindbrain 73 The Midbrain 73 The Forebrain 73

■ Q u i C k C o n C E P t C h E C k 3 . 2 : Understanding Drugs and Brain Functioning 74

Understanding the Neurochemistry of Psychoactive Drugs 74 Introducing Neurons 74 Neuronal Communication 75

Drug Influences on Neuronal Communication 76 The Major Neurotransmitters in Brief:

The Big Seven 76 Physiological Aspects of Drug-Taking Behavior 78

The Blood–Brain Barrier 78

■ d r u g s . . . i n f o C u s : Endorphins, Endocannabinoids, and the “Runner’s High” 79 Biochemical Processes Underlying Drug Tolerance 80

■ Q u i C k C o n C E P t C h E C k 3 . 3 : Understanding Cross-Tolerance and Cross-Dependence 80 Physiological Factors in Psychological Dependence 81

■ h E a L t h L i n E : Drug Craving and the Insula of the Brain 82

Psychological Factors in Drug-Taking Behavior 82 Expectation Effects 83

■ P o r t r a i t : Nora D. Volkow—A Scientist- General in the War on Drugs 84 Drug Research Procedures 85

Summary 85 / Key Terms 86 / Endnotes 86

Part two Legally restricted drugs in our society 89

Chapter 4

the Major stimulants: Cocaine and amphetamines 89

By the Numbers . . . 90 The History of Cocaine 90

Cocaine in Nineteenth-Century Life 91

Contents ■ ix

■ h E a L t h a L E r t : Cocaine after Alcohol: The Risk of Cocaethylene Toxicity 91 Freud and Cocaine 92

■ d r u g s . . . i n f o C u s : What Happened to the Coca in Coca-Cola? 93

■ Q u i C k C o n C E P t C h E C k 4 . 1 : Understanding the History of Cocaine 94

Acute Effects of Cocaine 94 Chronic Effects of Cocaine 95

■ h E a L t h a L E r t : The Physical Signs of Possible Cocaine Abuse 95

Medical Uses of Cocaine 96 How Cocaine Works in the Brain 96 Present-Day Cocaine Abuse 96

From Coca to Cocaine 97 From Cocaine to Crack 97

■ d r u g s . . . i n f o C u s : Crack Babies Revisited: What Are the Effects? 99

Patterns of Cocaine Abuse 100 Treatment Programs for Cocaine Abuse 100

■ d r u g s . . . i n f o C u s : Paco: A Cheap Form of Cocaine Floods Argentine Slums and Beyond 100

■ P o r t r a i t : Robert Downey Jr. and Others—Cleaning Up after Cocaine 101

Amphetamines 103 The Different Forms of Amphetamines 103 The History of Amphetamines 104 How Amphetamines Work in the Brain 104

Acute Effects of Amphetamines 104 Chronic Effects of Amphetamines 105

Methamphetamine Abuse 105 Present-Day Patterns of Methamphetamine Abuse 105

■ d r u g s . . . i n f o C u s : Methamphetamine and the Heartland of America 107 Methamphetamine-Abuse Treatment 107

■ Q u i C k C o n C E P t C h E C k 4 . 2 : Understanding Patterns of Cocaine and Methamphetamine Abuse 108

Medical Uses for Amphetamines and Similar Stimulant Drugs 108

■ h E a L t h L i n E : “Bath Salts” as a New Form of Stimulant Abuse 109 Stimulant Medications for ADHD 109 Other Medical Applications 110

Stimulant Medication and Cognitive Enhancement 111

Summary 111 / Key Terms 112 / Endnotes 112

■ P o i n t / C o u n t E r P o i n t i i : Should Cognitive Performance-Enhancing Drugs Be Used by Healthy People? 116

Chapter 5

Opioids: Opium, heroin, and Opioid pain Medications 118

By the Numbers . . . 119 Opium in History 119 The Opium War 121 Opium in Britain and the United States 122 Morphine and the Advent of Heroin 123 Opioids in American Society 124 Opioid Use and Heroin Abuse after 1914 124 Heroin Abuse in the 1960s and 1970s 125 Heroin and Other Opioids since the 1980s 126

■ Q u i C k C o n C E P t C h E C k 5 . 1 : Understanding the History of Opium and Opioids 127

Effects on the Mind and the Body 127 How Opioids Work in the Brain 128 Patterns of Heroin Abuse 129 Tolerance and Withdrawal Symptoms 130 The Lethality of Heroin Abuse 130

■ Q u i C k C o n C E P t C h E C k 5 . 2 : Understanding the Effects of Administering and Withdrawing Heroin 131

Heroin Abuse and Society 132 Treatment for Heroin Abuse 132

Heroin Detoxification 132 Methadone Maintenance 133 Alternative Maintenance Programs 134 Behavioral and Social-Community

Programs 134 Medical Uses of Opioid Drugs 134

■ h E a L t h a L E r t : Sustained-Release Buprenorphine: A New Era in Heroin-Abuse Treatment 135 Beneficial Effects 135

Prescription Pain Medication Misuse and Abuse 137 OxyContin Abuse 137 Responses to OxyContin Abuse 137

x ■ Contents

■ P o r t r a i t : David Laffer—Pharmacy Robber and Killer of Four 138 Abuse of Other Opioids Pain Medications 138 Prevalence of Nonmedical Use of Opioid Pain

Medications 138 Summary 139 / Key Terms 140 / Endnotes 140

Chapter 6

lsD and Other hallucinogens 143

By the Numbers . . . 144 A Matter of Definition 144 Classifying Hallucinogens 145 Lysergic Acid Diethylamide (LSD) 146

■ d r u g s . . . i n f o C u s : Strange Days in Salem: Witchcraft or Hallucinogens? 147 The Beginning of the Psychedelic Era 147

■ P o r t r a i t : Timothy Leary—Nutty Professor or Psychedelic Visionary? 149 Acute Effects of LSD 149 Effects of LSD on the Brain 150 Patterns of LSD Use 151

Facts and Fiction about LSD 151 Will LSD Produce Substance Dependence? 151 Will LSD Produce a Panic Attack or Psychotic

Behavior? 151 Will LSD Increase Your Creativity? 152 Will LSD Damage Your Chromosomes? 152

■ h E a L t h a L E r t : Emergency Guidelines for a Bad Trip on LSD 152 Will LSD Have Residual (Flashback) Effects? 153 Will LSD Increase Criminal or Violent Behavior? 153

Psilocybin and Other Hallucinogens Related to Serotonin 154 Lysergic Acid Amide (LAA) 154

■ h E a L t h L i n E : Bufotenine and the Bufo Toad 155 Dimethyltryptamine (DMT) 155 Harmine 156

Hallucinogens Related to Norepinephrine 156 Mescaline 156 DOM 156

■ d r u g s . . . i n f o C u s : Present-Day Peyotism and the Native American Church 157 MDMA (Ecstasy) 157

■ h E a L t h a L E r t : MDMA Toxicity: The Other Side of Ecstasy 158

Hallucinogens Related to Acetylcholine 159 Amanita muscaria 159 The Hexing Drugs and Witchcraft 159

Miscellaneous Hallucinogens 160 Phencyclidine (PCP) 161

Acute Effects of PCP 161

■ Q u i C k C o n C E P t C h E C k 6 . 1 : Understanding the Diversity of Hallucinogens 161

Patterns of PCP Abuse 162 Ketamine 162

■ Q u i C k C o n C E P t C h E C k 6 . 2 : Understanding PCP 163 Salvia divinorum 163

Summary 163 / Key Terms 165 / Endnotes 165

Chapter 7

Marijuana 167

By the Numbers . . . 168 A Matter of Terminology 168 The History of Marijuana and Hashish 170

Hashish in the Nineteenth Century 170 Marijuana and Hashish in the Twentieth Century 170 The Anti-Marijuana Crusade 171 Challenging Old Ideas about Marijuana 172

Acute Effects of Marijuana 172 Acute Physiological Effects 173 Acute Psychological and Behavioral Effects 173

■ Q u i C k C o n C E P t C h E C k 7 . 1 : Understanding the Effects of Marijuana 174

■ d r u g s . . . i n f o C u s : The Neurochemical “Yin and Yang” of Cannabis 175

Effects of Marijuana on the Brain 175 Chronic Effects of Marijuana 176

Tolerance 176 Withdrawal and Dependence 176 Cardiovascular Effects 177 Respiratory Effects and the Risk of Cancer 177 Effects on the Immune System 178 Effects on Sexual Functioning and Reproduction 178 Long-Term Cognitive Effects and the Amotivational

Syndrome 178

Contents ■ xi

The Gateway Hypothesis 179 The Sequencing Question 179 The Association Question 180 The Causation Question 180

■ Q u i C k C o n C E P t C h E C k 7 . 2 : Understanding the Adverse Effects of Chronic Marijuana Abuse 181

Patterns of Marijuana Smoking 181 Causes for Concern 182

■ h E a L t h a L E r t : A Synthetic Marijuana called Spice 182

Medical Marijuana 183 Muscle Spasticity and Chronic Pain 183

■ P o r t r a i t : Marcy Dolin—Marijuana Self-Medicator 183 Nausea and Weight Loss 184 The Medical Marijuana Controversy 184

The Issues of Decriminalization and Legalization 185 Summary 186 / Key Terms 187 / Endnotes 187

Part thrEE Legal drugs in our society 191

Chapter 8

alcohol: social Beverage/social Drug 191

By the Numbers . . . 192 What Makes an Alcoholic Beverage? 192 Alcohol Use through History 194

Alcohol in Nineteenth-Century America 194 The Rise of the Temperance Movement 195 The Road to National Prohibition 196 The Beginning and Ending of a “Noble

Experiment” 196 Present-Day Alcohol Regulation by Taxation 196

Patterns of Alcohol Consumption Today 197 Overall Patterns of Alcohol Consumption 197

■ h E a L t h L i n E : Multiple Ways of Getting a Standard Drink 198

■ d r u g s . . . i n f o C u s : Visualizing the Pattern of Alcohol Consumption in the United States 199 Problematic Alcohol Consumption among College

Students 200 Alcohol Consumption among Adolescents 200

■ Q u i C k C o n C E P t C h E C k 8 . 1 : Understanding Alcoholic Beverages 201

The Pharmacology of Alcohol 201 The Breakdown and Elimination of Alcohol 201 Measuring Alcohol in the Blood 202

■ h E a L t h L i n E : Gender, Race, and Medication: Factors in Alcohol Metabolism 203

Effects of Alcohol on the Brain 204 Acute Physiological Effects 204

Toxic Reactions 205 Heat Loss and the Saint Bernard Myth 205

■ h E a L t h a L E r t : Emergency Signs and Procedures in Acute Alcohol Intoxication 205 Diuretic Effects 206 Effects on Sleep 206 Effects on Pregnancy 206 Interactions with Other Drugs 206 Hangovers 206

Acute Behavioral Effects 207 Blackouts 208 Driving Skills 208

Preventing Alcohol-Related Traffic Fatalities among Young People 209

■ P o r t r a i t : Candace Lightner—Founder of MADD 209 Alcohol, Violence, and Aggression 210

■ d r u g s . . . i n f o C u s : Alcohol, Security, and Spectator Sports 211

■ d r u g s . . . i n f o C u s : Caffeine, Alcohol, and the Dangers of Caffeinated Alcoholic Drinks 212 Sex and Sexual Desire 212

Alcohol and Health Benefits 212

■ Q u i C k C o n C E P t C h E C k 8 . 2 : Understanding the Data from Balanced Placebo Designs 213

■ h E a L t h a L E r t : Guidelines for Responsible Drinking 214

Strategies for Responsible Drinking 215 Summary 215 / Key Terms 216 / Endnotes 216

Chapter 9

Chronic alcohol abuse and alcoholism 220

Alcoholism: Stereotypes, Definitions, and Life Problems 221

xii ■ Contents

By the Numbers . . . 221 Problems Associated with a Preoccupation with

Drinking 221 Emotional Problems 223 Vocational, Social, and Family Problems 223 Physical Problems 223

■ h E a L t h L i n E : A Self-Administered Short Michigan Alcoholism Screening Test (SMAST) 224 Hiding the Problems: Denial and Enabling 224

■ Q u i C k C o n C E P t C h E C k 9 . 1 : Understanding the Psychology of Alcoholism 225

Alcohol Abuse and Alcohol Dependence: The Health Professional’s Perspective 225

Physiological Effects of Chronic Alcohol Use 226 Tolerance and Withdrawal 226 Liver Disease 226 Cardiovascular Problems 227 Cancer 227 Dementia and Wernicke-Korsakoff

Syndrome 228 Fetal Alcohol Syndrome (FAS) 228

■ h E a L t h L i n E : Alcoholism Screening Instruments in Professional Use 230

Patterns of Chronic Alcohol Abuse 230 Gender Differences in Chronic Alcohol Use 231 Alcohol Abuse among the Elderly 231 The Family Dynamics of Alcoholism: A Systems

Approach 232 Children of an Alcoholic Parent or Parents 232

The Genetics of Alcoholism 233 The Concept of Alcoholism as a Disease 234 Approaches to Treatment for Alcoholism 235

Biologically Based Treatments 235

■ P o r t r a i t : Bill W. and Dr. Bob—Founders of Alcoholics Anonymous 237 Alcoholics Anonymous 237

■ h E a L t h L i n E : Is Controlled Drinking Possible for Alcoholics? 238

■ d r u g s . . . i n f o C u s : The Non-Disease Model of Alcoholism and Other Patterns of Substance Abuse 239

■ Q u i C k C o n C E P t C h E C k 9 . 2 : Understanding Alcoholics Anonymous 240 SMART Recovery 240

Chronic Alcohol Abuse and Alcoholism in the Workplace 240

Summary 241 / Key Terms 242 / Endnotes 242

■ P o i n t / C o u n t E r P o i n t i i i : Should Alcoholism Be Viewed as a Disease? 246

Chapter 10

nicotine and tobacco Use 248

By the Numbers . . . 249 Tobacco Use through History 249

Politics, Economics, and Tobacco 250 Snuffing and Chewing 250 Cigars and Cigarettes 250 Tobacco in the Twentieth Century 251

Health Concerns and Smoking Behavior 252

■ h E a L t h L i n E : African Americans, Smoking, and Mentholated Cigarettes 252

The Tobacco Industry Today 253 The Tobacco Settlement of 1998 254 The Tobacco Control Act of 2009 254 Tobacco Regulation and Global Economics 254

What’s in Tobacco? 254 Carbon Monoxide 255 Tar 255 Nicotine 256

The Dependence Potential of Nicotine 256 The Titration Hypothesis of Nicotine

Dependence 256 Tolerance and Withdrawal 257

Health Consequences of Tobacco Use 257

■ h E a L t h L i n E : Visualizing 400,000 to 440,000 Annual Tobacco-Related Deaths 257 Cardiovascular Disease 257 Respiratory Diseases 258 Lung Cancer 259 Other Cancers 259 Special Health Concerns for Women 260 The Hazards of Environmental Smoke 260

■ h E a L t h a L E r t : Signs of Trouble from Smokeless Tobacco 261

Patterns of Smoking Behavior and Use of Smokeless Tobacco 261

■ Q u i C k C o n C E P t C h E C k 1 0 . 1 : Understanding the Effects of Tobacco Smoking 262 The Youngest Smokers 262

Contents ■ xiii

Attitudes toward Smoking among Young People 262 Smokeless Tobacco 263 Cigars 264 Tobacco Use around the World 264

■ P o r t r a i t : Sigmund Freud—Nicotine Dependence, Cigars, and Cancer 265

Quitting Smoking: The Good News and the Bad 265 The Good News: Undoing the Damage 266 The Bad News: How Hard It Is to Quit 266

■ h E a L t h L i n E : How to Succeed in Quitting Smoking—By Really Trying 268 Nicotine Gums, Patches, Sprays, and Inhalers 268 The Role of Physicians in Smoking Cessation 268 A Final Word 269

Summary 270 / Key Terms 271 / Endnotes 271

Chapter 11

Caffeine 275

Coffee 276 By the Numbers . . . 276

Coffee in Britain and North America 276 Major Sources of Coffee 277 The Caffeine Content in Coffee 277

■ d r u g s . . . i n f o C u s : Why There Are No (Live) Flies in Your Coffee 278

Tea 278 Tea in Britain and North America 278 The Chemical Content in Tea 279

Chocolate 279 How Chocolate Is Made 280 The Chocolate Industry Today 280 The Xanthine Content in Chocolate 280

■ h E a L t h L i n E : Chocolate, Flavanols, and Cardiovascular Health 281

Soft Drinks 281 Caffeine from OTC Drugs and Other Products 281

■ P o r t r a i t : Milton S. Hershey and the Town Built on Chocolate 282

Caffeine as a Drug 282

■ Q u i C k C o n C E P t C h E C k 1 1 . 1 : Understanding Caffeine Levels in Foods and Beverages 283 Effects of Caffeine on the Body 283 Effects of Caffeine on Behavior 283

Potential Health Benefits 284 Potential Health Risks 285

Cardiovascular Effects 285 Osteoporosis and Bone Fractures 285

■ h E a L t h L i n E : Coffee, Genes, and Heart Attacks 286 Breast Disease 286 Effects during Pregnancy and Breastfeeding 286 Panic Attacks 286

Dependence, Acute Toxicity, and Medical Applications 287 Tolerance 287 Withdrawal 287 Craving 287 Acute Toxicity of Caffeine 287 Prescription Drugs Based on Xanthines 288

Caffeine and Young People: A Special Concern 288

■ d r u g s . . . i n f o C u s : Energy Shots 289 Summary 289 / Key Terms 290 / Endnotes 290

Part four Enhancers and depressants 293

Chapter 12

performance-enhancing Drugs and Drug testing in sports 293

Drug-Taking Behavior in Sports 294 By the Numbers . . . 294

What Are Anabolic Steroids? 294 Anabolic Steroids at the Modern Olympic Games 295

■ P o r t r a i t : Lance Armstrong: From Honor to Dishonor 297 Anabolic Steroids in Professional and Collegiate Sports 297

Performance-Enhancing Drug Abuse and Baseball 297

■ d r u g s . . . i n f o C u s : Suspension Penalties for Performance-Enhancing Drug Use in Sports 298

The Hazards of Anabolic Steroids 299 Effects on Hormonal Systems 299 Effects on Other Systems of the Body 300 Psychological Problems 300 Special Problems for Adolescents 301

■ Q u i C k C o n C E P t C h E C k 1 2 . 1 : Understanding the Effects of Anabolic Steroids 301

xiv ■ Contents

Patterns of Anabolic Steroid Abuse 301 The Potential for Steroid Dependence 302 Counterfeit Steroids and the Placebo Effect 303

■ h E a L t h a L E r t : The Symptoms of Steroid Abuse 304

Nonsteroid Hormones and Performance-Enhancing Supplements 304 Human Growth Hormone 304 Dietary Supplements as Performance-Enhancing

Aids 305 Nonmedical Use of Stimulant Medication in

Baseball 306 Current Drug-Testing Procedures and Policies 306

The Forensics of Drug Testing 306

■ d r u g s . . . i n f o C u s : Pharmaceutical Companies and Anti-Doping Authorities: A New Alliance 307 Sensitivity and Specificity 308 Masking Drugs and Chemical Manipulations 308 Pinpointing the Time of Drug Use 309

■ Q u i C k C o n C E P t C h E C k 1 2 . 2 : Understanding Drug Testing 310

The Social Context of Performance-Enhancing Drugs 310

Summary 311 / Key Terms 312 / Endnotes 312

Chapter 13

Depressants and inhalants 315

By the Numbers . . . 316 Barbiturates 316

Categories of Barbiturates 317 Acute Effects of Barbiturates 317

■ d r u g s . . . i n f o C u s : Is There Any Truth in “Truth Serum”? 318 Chronic Effects of Barbiturates 319 Current Medical Uses of Barbiturates 319 Patterns of Barbiturate Abuse 319

Nonbarbiturate Sedative-Hypnotics 320 The Development of Antianxiety Drugs 320 Benzodiazepines 321

Medical Uses of Benzodiazepines 321 Acute Effects of Benzodiazepines 322 Chronic Effects of Benzodiazepines 322 How Benzodiazepines Work in the Brain 323 Patterns of Benzodiazepine Misuse and Abuse 323

Nonbenzodiazepine Depressants 324

■ h E a L t h a L E r t : The Dangers of Rohypnol as a Date-Rape Drug 324 Zolpidem and Eszopiclone 325 Buspirone 325 Beta Blockers 325 Antidepressants 325

■ Q u i C k C o n C E P t C h E C k 1 3 . 1 : Understanding the Abuse Potential in Drugs 326

A Special Alert: The Risks of GHB 326 Acute Effects 326 Protective Strategies for Women 326

■ P o r t r a i t : Patricia White, GHB, and the “Perfect” Crime 326

Inhalants through History 327 Nitrous Oxide 328 Ether 329

Glue, Solvent, and Aerosol Inhalation 329 The Abuse Potential of Inhalants 329 Acute Effects of Glues, Solvents, and Aerosols 330 The Dangers of Inhalant Abuse 330

■ h E a L t h a L E r t : The Signs of Possible Inhalant Abuse 330

Patterns of Inhalant Abuse 331

■ d r u g s . . . i n f o C u s : Resistol and Resistoleros in Latin America 332 The Dependence Potential of Chronic Inhalant

Abuse 333 Responses of Society to Inhalant Abuse 333

■ Q u i C k C o n C E P t C h E C k 1 3 . 2 : Understanding the History of Inhalants 334

Summary 334 / Key Terms 335 / Endnotes 336

Part five Medicinal drugs 339

Chapter 14

prescription Drugs, Over-the- Counter Drugs, and Dietary supplements 339

By the Numbers . . . 340 The History of Prescription Drug Regulations 341 Procedures for Approving Prescription Drugs 342

Phases of Clinical Testing for Prescription Drugs 342 Patents and Generic Forms of Prescription Drugs 344

Contents ■ xv

Speeding Up the FDA Approval Process 344 Procedures for Approving OTC Drugs 345

Are FDA-Approved Drugs Safe? 346

■ Q u i C k C o n C E P t C h E C k 1 4 . 1 : Understanding the FDA Approval Process 346 The Issue of Speed versus Caution 346 Patterns of Prescription Drug Misuse 347 Unintentional Drug Misuse through Prescription

Errors 347

■ h E a L t h L i n E : The Potential for Death by Prescription Error 348

■ h E a L t h L i n E : Doctor Shopping for Prescription Drugs 349 Patterns of Prescription Drug Abuse 349

Major OTC Analgesic Drugs 349 Aspirin 350 Acetaminophen 351 Ibuprofen 351 Naproxen 352 OTC Analgesic Drugs and Attempted Suicide 352

■ Q u i C k C o n C E P t C h E C k 1 4 . 2 : Understanding OTC Analgesic Drugs 352

Other Major Classes of OTC Drugs 352 Sleep Aids 352 Cough-and-Cold Remedies 353

The Pharmaceutical Industry Today 353

■ P o r t r a i t : Ryan Haight and the Ryan Haight Act of 2008 354

Dietary Supplements 355

■ d r u g s . . . i n f o C u s : What We Know about Nine Herbal Supplements 356

Summary 357 / Key Terms 358 / Endnotes 358

■ P o i n t / C o u n t E r P o i n t i v : Should Prescription Drugs Be Advertised to the General Public? 360

Chapter 15

Drugs for treating schizophrenia and Mood Disorders 362

The Biomedical Model 363 By the Numbers . . . 363 Antipsychotic Drugs and Schizophrenia 364 The Symptoms of Schizophrenia 364

The Early Days of Antipsychotic Drug Treatment 364

■ h E a L t h L i n E : Mercury Poisoning: On Being Mad As a Hatter 365 Antipsychotic Drug Treatment 365 First-Generation Antipsychotic Drugs 365 Second-Generation Antipsychotic Drugs 366 Third-Generation Antipsychotic Drugs 367 Effects of Antipsychotic Drugs on the Brain 367

Drugs Used to Treat Depression 368

■ P o r t r a i t : The Melancholy President— Abraham Lincoln, Depression, and Those “Little Blue Pills” 369 First-Generation Antidepressant Drugs 369 Second-Generation Antidepressant Drugs 370 Third-Generation Antidepressant Drugs 370

■ h E a L t h a L E r t : SSRI Antidepressants and Elevated Risk of Suicide among Children and Adolescents 371 Effects of Antidepressant Drugs on the Brain 371 The Effectiveness of Specific Antidepressant Drugs 372

Drugs for Other Types of Mental Disorders 372 Mania and Bipolar Disorder 372

■ Q u i C k C o n C E P t C h E C k 1 5 . 1 : Understanding the Biochemistry of Mental Illness 373 Autism 373 Off-Label Usage of Psychotropic Medications 374

Psychiatric Drugs, Social Policy, and Deinstitutionalization 374

■ d r u g s . . . i n f o C u s : Psychiatric Drugs and the Civil Liberties Debate 375

Summary 375 / Key Terms 376 / Endnotes 376

Part six Prevention and treatment 379

Chapter 16

substance-abuse prevention 379

By the Numbers . . . 380 Levels of Intervention in Substance-Abuse

Prevention 380

■ Q u i C k C o n C E P t C h E C k 1 6 . 1 : Understanding Levels of Intervention in Substance- Abuse Prevention Programs 381

Strategies for Substance-Abuse Prevention 381 Resilience and Primary Prevention Efforts 382

xvi ■ Contents

Measuring Success in a Substance-Abuse Prevention Program 382

A Matter of Public Health 382

■ h E a L t h L i n E : The Public Health Model and the Analogy of Infectious Disease Control 383

■ P o r t r a i t : Dr. A. Thomas McLellan Goes to Washington (Briefly) 384

Lessons from the Past: Prevention Approaches That Have Failed 384 Reducing the Availability of Drugs 384 Punitive Measures 385 Scare Tactics and Negative Education 385 Objective Information Approaches 386 Magic Bullets and Promotional Campaigns 386 Self-Esteem Enhancement and Affective

Education 386 Hope and Promise: Components of Effective School-Based

Prevention Programs 387 Peer-Refusal Skills 387 Anxiety and Stress Reduction 387 Social Skills and Personal Decision Making 387 An Example of an Effective School-Based Prevention

Program 387

■ h E a L t h L i n E : Peer-Refusal Skills: Ten Ways to Make It Easier to Say No 388 Drug Abuse Resistance Education (D.A.R.E.) 389

■ Q u i C k C o n C E P t C h E C k 1 6 . 2 : Understanding Primary Prevention and Education 389 Community-Based Prevention Programs 390 Components of an Effective Community-Based

Program 390 Alternative-Behavior Programming 391 The Influence of Media 391 An Example of an Effective Community-Based Prevention

Program 391 Family Systems in Primary and Secondary

Prevention 392 Special Role Models in Substance-Abuse Prevention 392

■ d r u g s . . . i n f o C u s : Substance Use and Abuse among Young Mothers 393 Parental Communication in Substance-Abuse

Prevention 393 The Triple Threat: Stress, Boredom, and Spending

Money 394 Multicultural Issues in Primary and Secondary

Prevention 394 Prevention Approaches in Latino Communities 394

Prevention Approaches in African American Communities 395

Substance-Abuse Prevention in the Workplace 395 The Economic Costs of Substance Abuse in the

Workplace 396 Drug Testing in the Workplace 396 The Impact of Drug-Free Workplace Policies 397

Yes, You: Substance-Abuse Prevention and the College Student 397 Changing the Culture of Alcohol and Other Drug Use in

College 398 Substance-Abuse Prevention on College Campuses 398

■ h E a L t h L i n E : Alcohol 101 on College Campuses 399

Substance-Abuse Prevention Information 399 Summary 400 / Key Terms 401 / Endnotes 401

■ P o i n t / C o u n t E r P o i n t v : Should We Continue to D.A.R.E. or Should We Give it up? 405

Chapter 17

substance-abuse treatment: strategies for Change 407

By the Numbers . . . 408 Designing Effective Substance-Abuse Treatment

Programs 409 The Biopsychosocial Model for Substance-Abuse

Treatment 409 Intervention through Incarceration and Other Punitive

Measures 409 Substance-Abuse Treatment and Law Enforcement 410

■ d r u g s . . . i n f o C u s : Penalties for Crack versus Penalties for Powder Cocaine: Correcting an Injustice 413 Prison-Alternative Treatment Programs 414 Drug Courts 414

■ P o r t r a i t : Monsignor William O’Brien— Founder of Daytop Village 415 Prison-Based Treatment Programs 416

Substance-Abuse Treatment in the Workplace 416 The Personal Journey to Treatment and Recovery 417

Rehabilitation and the Stages of Change 417 Stages of Change and Other Problems in Life 418

■ Q u i C k C o n C E P t C h E C k 1 7 . 1 : Understanding the Stages of Change in Substance- Abuse Treatment 419

Contents ■ xvii

The Impact of Family Systems on Treatment and Recovery 419 Family Dynamics in Drug Abuse 419 Enabling Behaviors as Obstacles to Rehabilitation 420 Survival Roles and Coping Mechanisms 421 Resistance at the Beginning, Support along

the Way 421 Finding the Right Substance-Abuse Treatment

Program 421 Judging the Quality of the Treatment Facility 422

Principles to Maximize the Chances of Successful Treatment 423

Needing versus Receiving Substance-Abuse Treatment 423

A Final Note: For Those Who Need Help . . . 424 Summary 425 / Key Terms 426 /

Endnotes 426

Credits 429 index 433

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Preface ■ xix

In today’s world, drugs and their use have the potential for good and for bad. As a society and as indi- viduals, we can be the beneficiaries of drugs—or their victims. This perspective continues to be the mes- sage of Drugs, Behavior, and Modern Society, Eighth Edition. As has been the case since the first edition, this book introduces the basic facts and major issues con- cerning drug-taking behavior in a straightforward, com- prehensive, and reader-friendly manner. A background in biology, sociology, psychology, or chemistry is not necessary. The only requirement is a sense of curiosity about the range of chemical substances that affect our minds and our bodies and an interest in the challenges these substances bring to our society and our daily lives. These challenges can be framed in terms of three fun- damental themes.

The role of drug-taking behavior throughout history— First of all, present-day issues concerning drug misuse and abuse are issues that society has confronted for a long time. Drugs and drug-taking behavior are conse- quences of a particularly human need to feel stronger, more alert, calmer, more distant and dissociated from our surroundings, or simply good. It is the misuse and abuse of chemical substances to achieve these ends that have resulted in major problems in the United States and around the world. The diversity in psychoactive drugs in our society— There is an enormous diversity among drugs that affect the mind and the body. We need to educate ourselves not only about illicit drugs such as cocaine, amphetamines, heroin, hallucinogens, and marijuana but also about legally available drugs such as alcohol, nicotine, and caffeine. Drugs, Behavior, and Modern Society has been designed as a comprehensive survey of all types of psychoactive drugs, addressing the issues of drug-taking behavior from a combination of psy- chological, biological, and sociological perspectives. The personal impact of drug-related issues in our lives— Finally, we need to recognize that, like it or not, the decision to use drugs is one of life’s choices in contem- porary society, regardless of our racial, ethnic, or reli- gious background, how much money we have, where we live, how much education we have acquired, whether we are male or female, and whether we are young or old. The potential for misuse and abuse is a problem facing all of us.

new to this edition

The Eighth Edition of Drugs, Behavior, and Modern Society is divided into six sections:

Part One (Chapters 1–3): Drugs in Society/Drugs in Our Lives Part Two (Chapters 4–7): Legally Restricted Drugs in Our Society Part Three (Chapters 8–11): Legal Drugs in Our Society Part Four (Chapters 12 and 13): Enhancers and Depressants Part Five (Chapters 14 and 15): Medicinal Drugs Part Six (Chapters 16 and 17): Prevention and Treatment

As you will see, chapters about particular drugs have been grouped not in terms of their pharmacological or chemical characteristics but, rather, in terms of how readily accessible they are to the general public and today’s societal attitudes toward their use. The last sec- tion of the book concerns itself with prevention and treatment. In addition, several special features through- out the book will enhance your experience as a reader and serve as learning aids.

This text is available in a variety of formats—digital and print. To learn more about our programs, pricing options, and customization, visit www.pearsonhighered .com.

By the numbers . . . At the beginning of each chapter, a feature called By the Numbers . . . provides an often surprising and provoca- tive insight into current viewpoints and research. It is pre- sented in a brief, quantitative format that draws you into the chapter and sets the stage for further exploration.

Quick Concept Checks Sometimes, when the material gets complicated, it is good to have a quick way of finding out whether you understand the basic concepts being explained. Each chapter of this book includes, from time to time, a Quick Concept Check, where you can see in a minute

PrEfaCE

xx ■ Preface

or two where you stand. Some of the Checks are in a matching format; others involve interpreting a graph or diagram. In some cases, you will be asked to apply the principles you have learned to a real-world situation.

portraits Seventeen Portrait features, one in each chapter, take you into the lives of individuals who either have influenced our thinking about drugs in our society or have been affected by drug use or abuse. Some of these people are known to the public at large, but many are not. The subjects of these Portraits include a brutal drug trafficker (Pablo Escobar, Chapter 2), a movie star (Robert Downey Jr., Chapter 4), a convicted killer (David Laffer, Chapter 5), a cultural icon (Timothy Leary, Chapter 6), and a depressive U.S. President (Abraham Lincoln, Chapter 13). All the Por- traits put a human face on discussions of drugs and behav- ior. They remind us that we are dealing with issues that affect real people in all walks of life, now and in the past.

Drugs . . . in Focus There are many fascinating stories to tell about the role of drugs in our history and our present-day culture, along with important facts and serious issues surround- ing drug use. A total of 26 Drugs . . . in Focus features are presented in the Eighth Edition. The topics of these features cover a wide range, from questions about the origins of the word coca in Coca-Cola (Chapter 4) and possible hallucinogenic witchcraft in seventeenth cen- tury Salem, Massachusetts, (Chapter 6), to future possi- bilities of gene doping in the Olympics (Chapter 12) and the present-day use of “truth serum” in terrorist interro- gations (Chapter 13).

health line Helpful information regarding the effectiveness and safety aspects of particular drugs, specific aspects of drug-taking behavior, and new medical applications can be found in 22 Health Line features throughout the book. Health Line topics include understanding the neurological basis for drug craving (Chapter 3), the controversy over the use of stimulant medications as “smart pills” (Chapter 4), con- cerns over a new synthetic marijuana called Spice (Chap- ter 7), the risks of smoking mentholated cigarettes among African Americans (Chapter 10), “doctor-shopping” and prescription pain medications (Chapter 14), and alcohol prevention programs like Alcohol 101 on college cam- puses (Chapter 16), to name a few.

health alert Information of a more urgent nature is provided in 14  Health Alert features. You will find important facts that you can use to recognize the signs of drug misuse or abuse and ways in which you can respond to emergency drug-taking situations, as well as useful Internet links where you can go for assistance. Health Alert topics in the Eighth Edition include strategies to avoid adverse effects of drug-drug and food-drug combinations (Chapter 3), the risks of cocaine com- bined with alcohol (Chapter 4), emergency guide- lines for adverse reactions to LSD (Chapter 6) or alcohol (Chap ter 8), and the dangers of Rohypnol as a date-rape drug (Chapter 13).

point/Counterpoint Debates Drug issues are seldom black or white, right or wrong. Some of the most hotly debated questions of our day concern the use, misuse, and abuse of drugs. These issues deserve a good deal of critical thought. This is why at specific locations in this book, I have taken five important controversies concerning drugs, collected the key viewpoints pro and con, and created a Point/ Counterpoint debate based on a simulated conversa- tion that two hypothetical people might have on that question. The Point/Counterpoint features appear at the end of the chapter that deal specifically with the controversy addressed in the debate. I invite you to read these debates carefully and try to arrive at your own position, as an exercise in critical thinking. Along with considering the critical thinking questions for further discussion that follow each Point/Counter- point feature, you may wish to continue the debate in your class.

supplements Pearson Education is pleased to offer the following sup- plements to qualified adopters.

instructor’s Manual and test Bank (0-205-04839-0) This Instructor’s Manual and Test Bank provides instructors with support material, classroom enrich- ment inform ation, and wealth of assessment questions. Corresponding to the chapters in the text, each of the manual’s 17 chapters contains discussion questions, lec- ture outlines, video suggestions, and a test bank, which

includes an extensive set of multiple choice, true/false and essay questions.

Mytest test Bank (0-205-04837-4) This test bank is available in computerized format, which allows instructors to easily create and print quiz- zes and exams. Questions and tests can be authored online, allowing instructors ultimate flexibility and the ability to efficiently manage assessments anytime, anywhere. Instructors can easily access existing ques- tions, edit, create, and store using simple drag and drop Word-like controls. For more information, go to www.PearsonMyTest.com.

powerpoint presentation (0-205-04836-6) The PowerPoint Presentation is an exciting interactive tool for use in the classroom. Each chapter pairs key concepts with images from the textbook to reinforce student learning.

Mypsychlab (www.mypsychlab.com) This online study resource offers a wealth of anima- tions and practice tests, plus additional study and research tools. With this edition, there are now new assessments, web and video/media links, and flash cards. www.pearsonhighered.com

an invitation to readers

I welcome your reactions to Drugs, Behavior, and Mod- ern Society, Eighth Edition. Please send any comments or questions to the following address: Dr. Charles F.  Levinthal, Department of Psychology, 135  Hofstra University, Hempstead, NY 11549. You can also com- municate by fax at 516 463-6052 or at the following email address: [email protected]. I look forward to hearing from you.

acknowledgments

In the course of writing the Eighth Edition, I have received much encouragement, assistance, and expert advice from a number of people. I have benefited from their generous

sharing of materials, knowledge, and insights. I am par- ticularly indebted to Dr. Elizabeth Crane, Substance Abuse and Mental Health Services Administration, U.S. Department of Health and Human Services; Charles F. Miller, Office of Policy and Interagency Affairs, National Drug Intelligence Center, U.S. Department of Justice; Dr. Patrick M. O’Malley, Institute for Social Research, The University of Michigan, Ann Arbor; and Lawrence Payne, Office of Public Affairs, Drug Enforcement Administration, U.S. Department of Justice.

I am fortunate to have worked with a superb team at Pearson. I am especially indebted to my editor, Susan Hartman, my program manager, Reena Dalal, and my senior project manager, Revathi Viswanathan. Their professionalism and talents contributed so much to the production quality of this book and are greatly appreciated. A number of manuscript reviewers made invaluable suggestions as I worked on the Eighth Edition. I thank all of them for their help: Marge Murray- Davis, Minnesota State University; Philip Langlais, Old Dominion University; Robin Joynes, Kent State University; Chris Jones-Cage, College of the Desert; Susan Fellows, California State University, Dominguez Hills; Toni Watt, Texas State University; Larry Ashley, University of Nevada; Frank White, University of North Dakota; Jennifer Graham, Penn State University; Christopher Goode, Georgia State University; Andy Harcrow, The University of Alabama; Robert Carr, University of South Dakota; John Gampher, University of Alabama at Birmingham; Bengie Cravey, Darton State College; Lee Ancona, University of North Texas; Sidney Auerbach, Rutgers University; Christopher Correia, Auburn University; Perry Fuchs, UT Arlington; Edith Ellis, College of Charleston; Neil Rowland, University of Florida; William Cabin, Richard Stockton College.

On a more personal note, there are others who have given me their support over the years and to whom my appreciation goes beyond words. As always, I thank my mother-in-law, Selma Kuby, for her encouragement and love.

Above all, my family has been a continuing source of strength. I will always be grateful to my sons David and Brian, and to my daughters-in-law Sarah and Karen, for their love and understanding. I am especially grate- ful to my wife, Beth, for her abiding love, support, and complete faith in my abilities. The Eighth Edition is dedicated to my grandsons, Aaron Matthew Levinthal and Michael Samuel Levinthal.

Charles F. Levinthal

Preface ■ xxi

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1

Mike was seventeen, soon to be a high school senior—an

age when life can be both terrific and terrifying. He looked

at me with amazement, telling me by his expression that

either the question I was asking him was ridiculous, or the

answer was obvious. “Why do kids do drugs?” I had asked.

“It’s cool,” he said. “That’s why. Believe me, it’s impor-

tant to be cool. Besides, in my life, drugs just make me feel

better. Smoking some weed, chilling out with a little Vicodin,

spinning with some Addies—it’s a way of getting away from

stuff. You know that everybody does it. At least all of my

friends do it. And it’s easy to get them. A helluva lot easier

than beer.”

The conversation was over. But as he started to leave,

Mike seemed to notice the concern on my face. “Don’t

worry about me,” he said with a smile, “I can handle it.

I can handle it just fine.”

After you have completed this chapter, you should have an understanding of

▶ Basic terminology concerning drugs and drug-taking behavior

▶ The origins and history of drugs and drug-taking behavior

▶ Present-day patterns of drug use in the United States

▶ Risk factors and protective factors for drug-taking behavior

▶ Current problems with club drugs and the nonmedical use of prescription pain relievers and prescription stimulant medications

C h a p t e r

1

Part One

Drugs in Society/Drugs in Our Lives

Drugs and Behavior Today

2 ■ Part One Drugs in Society/Drugs in Our Lives

There is no question that we live in a world where drugs are all around us. Thousands of Internet web sites offering information about drug use are just a click away. We are continually bombarded with news about drug-related arrests of major drug traffickers and ordinary citizens, news about popular celebrities and their latest involvement with drugs, news about drugs intercepted and confiscated at our borders and widespread drug use in the major cities and small towns of America.

It also seems impossible to avoid the reality of drugs in our personal lives. One in four adults in the United States, according to one survey, report that drugs have been a cause of trouble in their family. At a time when the economy and related matters dominate our concerns about the present and the future, about two out of three Americans continue to worry about drug use either a fair amount of time or a great deal. In school, you have been taught the risks involved in drug use, and most of you have contended with the social pressure to engage in drug-taking behavior with your friends. You may or may not have been success- ful in doing so. You also may have noticed your lo- cal pharmacy starting to look increasingly like a bank, with the installation of panic alarms, bulletproof glass, and security cameras, as pharmacists turn to protect- ing themselves from people robbing them for their supplies of oxycodone and other prescription pain medications.1

Making matters more complicated and difficult for us, drug-related problems in our contemporary

society extend beyond illegal drugs such as heroin, cocaine, amphetamines, LSD and other hallucino- gens, and (except for certain U.S. states) marijuana. In fact, while many of these drugs continue to wreak havoc on lives and communities throughout America, it can be argued that the adverse effects associated with legally sanctioned drugs such as alcohol, nico- tine, and certain prescription and nonprescription medications are more far-reaching. The abuse of these drugs affects far greater numbers of people, de- spite our efforts to regulate their use. Here are some facts about legally sanctioned drugs as we proceed through the second decade of the twenty-first cen- tury in America:

■ Regular consumption of alcohol often begins in junior high school or earlier, despite the fact that twenty-one is the minimum legal age for purchas- ing alcoholic beverages. In the United St ates alone, more than 38 million adults, 1 in 6 in the population, admit to having binged on alcohol at least four times in the last month, with more than 80,000  deaths each year attributed to excessive drinking. One in 10 children and teenagers in the United States (about 7.5 million) live with at least one parent who has an alcohol problem. On college campuses nationwide, binge drinking continues to be a major problem and a significant factor in date- rape assaults and other forms of violent behavior (Chapter 8). We pay a heavy price for problems as- sociated with chronic alcohol abuse and alcoholism on a social and personal level (Chapter 9).

■ About one in eleven high school seniors report smoking cigarettes daily, despite the fact that it is ille- gal for those younger than 18 years old (19 years old in some U.S. states) to purchase tobacco products. While the current prevalence rate is less than half the prevalence rate in 1990s when the figure was about 1 in 5, underage smoking remains a significant public-health issue (Chapter 10)—for good reason. Nearly 80 percent of all adult smokers smoked their first cigarette and became regular smokers before they were 18 years old.2

■ Prescription drug abuse, particularly with respect to pain medications such as oxycodone and hydro- codone (Chapter 5), has reached epidemic propor- tions. In New York State alone, prescriptions for pain medication have risen 82 percent from 2007 to 2010, along with significant increases in hospital admissions and deaths due to nonmedical use of these drugs. Since 2008, unintentional drug poison- ing (principally from prescription medications) has

by the numbers . . .

61,533 On an average day in 2011, the number of U.S. adolescents, aged 12 to 17 years old, who binged on alcohol

3,192 The number in 2011 who smoked a cigarette for the first time. Average age: 17.2 years old.

449,000,000 The number of results that come up from searching the word “drugs” on Google.®

Source: Information from the Google® search engine, 2013. Substance Abuse and Mental Health Services Administration (2012). Results from The 2011 National Survey on Drug Use and Health: Detailed Tables. Rockville, MD: Substance Abuse and Mental Health Services Administration, Tables 2.73A and 4.6B.

Chapter 1 Drugs and Behavior today ■ 3

become the leading cause of injury death among people 25 to 64 years old, exceeding fatalities due to motor vehicle accidents. Nationwide, more than 700 pharmacies in 2012 experienced an armed robbery specifically for prescription drugs, about twice as many as in 2006.3

It will be important, therefore, to address the issues of drugs that are legally sanctioned in our society as well as drugs that are not.

Whether we like it or not, the decision to use drugs of all types and forms, legally sanctioned or not, has become one of life’s choices in America, as well as in societies around the world. Every segment of so- ciety is affected. The availability of drugs and the po- tential for drug abuse present a challenge for people of all ages, from the young to the elderly. The conse- quences of drug-taking behavior can be observed in the workplace and retirement communities as well as on street corners, in school yards, and on college campuses. Drug use is going on in the homes of every community, large or small. The social and personal problems associated with drug use extend in one way or another to men and women of all ethnic and racial groups, geographic regions, and socioeconomic levels. No groups and no individuals should believe them- selves exempt.4

The purpose of this book is to answer your ques- tions and address your concerns about the wide range of drugs and the many forms of drug-taking behavior in our society today. You might even find answers to ques- tions you never thought about.

Social Messages about Drug Use

Unfortunately, we live in a social environment that sends us mixed messages about drug-taking behavior. The im- ages of Joe Camel, the Marlboro Man, and the Virginia Slims Woman in print advertisements for cigarettes are remnants of an increasingly distant past, but at one time they were iconic (and highly effective) symbols in mar- keting campaigns designed to convey the attractiveness of smoking to the public, particularly to young people. They are gone now as a result of federal regulations over cigarette advertising that were established in 1998. For decades, warning labels on cigarette packs and public service announcements have cautioned us about the se- rious health hazards of tobacco use, but the fact remains that about one in four adult Americans today are cur- rent cigarette smokers, and the prevalence rate has been slow to decline (see Chapter 10).

Beer commercials during telecasts of football games and other athletic events are designed to be entertaining and to associate beer drinking with a lifestyle filled with fun, friendship, sex, and romance, but we are expected to abide by the tagline at the end of the ad to “drink respon- sibly” or “know when to say when.” The ramifications of the social messages inherent in these commercials are significant. It has been established that the degree of positive expectancies about alcohol (viewing drinking as a way of gaining social acceptance, for example) predicts the onset age of drinking and the tendency to engage in high-risk alcohol use over time (see Chapter 8).

Major political figures, including U.S. presidents and vice presidents, as well as candidates for these offices and a host of public officials on local and national levels, have admitted smoking marijuana earlier in their lives. In recent years, regulatory policy in some U.S. states has changed dramatically, making marijuana legally avail- able either for medical purposes or general use by adults. Yet the U.S. federal government position on marijuana remains unchanged, stipulating that the drug is an illegal substance, officially classified since 1970 as a Schedule I controlled substance, defined as a drug with a high po- tential for abuse and no accepted medical use—in the same category as heroin (see Chapters 2 and 7).

Anti-drug media campaigns are designed to dis- courage young people from becoming involved with drugs in general. At the same time, we observe a never- ending stream of sports figures, entertainers, and other high-profile individuals engaging in drug-taking be- havior. Even though the careers of these people are frequently jeopardized, and in some instances, lives

The nonmedical use of prescription medications has become a significant public health concern. In 2011, an estimated 24 million Americans over the age of 26 reported using a pain medication for nonmedical reasons at some point in their lifetime.

4 ■ Part One Drugs in Society/Drugs in Our Lives

are lost (see Chapter 2), powerful pro–drug-use mes- sages continue to influence us. These messages come from the entertainment industry and traditional media sources, as well as from web sites on the Internet.5 As confusing and often contradictory as these messages are, they represent the present-day drug scene in America.

Two Ways of Looking at Drugs and Behavior

In the chapters ahead, we will look at the subject of drugs and behavior in two basic ways.

First, we will examine the biological, psychological, and sociological effects of consuming certain types of drugs. The focus will be on the study of specific sub- stances that alter our feelings, our thoughts, our percep- tions of the world, and our behavior. These substances are referred to as psychoactive drugs because they have the ability to alter the functioning of the brain and hence produce changes in our behavior and experience.

Psychoactive drugs that traditionally receive the great- est amount of attention are referred to as illicit (illegal) drugs. Criminal penalties are imposed in the United States on their possession, manufacture, or sale. The best- known examples are heroin, cocaine, and (except in some U.S. states) marijuana, as well as a wide range of so-called “club drugs,” such as methamphetamine (meth), Ecstasy, LSD, PCP, ketamine, and GHB. Other equally important psychoactive substances, however, are licit (legal) drugs, such as alcohol, nicotine, caffeine, and certain prescrip- tion medications. In the cases of alcohol and nicotine, legal access carries a minimum-age requirement.

Second, we will focus on the complex interplay of circumstances in our lives that lead to drug-taking behavior. We will examine the possibility that drug use is, at least in part, a consequence of how we feel about ourselves in relation to our family, friends, and acquaintances, to our life experiences, and to the community in which we live. We will also examine

the biological factors that may predispose us to drug- taking behavior. An exploration into the reasons why some individuals engage in drug-taking behavior, whereas others do not, will be a primary topic of discussion.

Understanding the interplay between drug-tak- ing behavior and society is essential when we con- sider the dangerous potential for drug use to become drug dependence. As many of us know all too well, a vicious circle can develop in which drug-taking be- havior fosters more drug-taking behavior, in a spiral- ing pattern that can be extremely difficult to break. Individuals showing signs of drug dependence dis- play intense cravings for the drug and, in many cases, require increasingly greater quantities to get the same, desired effect. They become preoccupied with their drug-taking behavior, and it becomes evi- dent that their lives have gotten out of control (see Chapter 2).

Ultimately, an understanding of drug dependence requires an examination of biological as well as psycho- logical and sociological factors (see Figure 1.1). On a biological level, the use of psychoactive drugs modifies the functioning of the brain, both during the time when

Society

Physiological Impact on the Brain

Psychoactive Drugs

Biological Factors

Psychological Factors

Sociological Factors

Drug-Taking Behavior

F i g u r e 1 . 1

The Biopsychosocial Model: Understanding the interplay of drugs, behavior, and society.

psychoactive drugs: Drugs that affect feelings, thoughts, perceptions, or behavior.

illicit drugs: Drugs whose manufacture, sale, or possession is illegal.

licit drugs: Drugs whose manufacture, sale, or possession is legal.

drug dependence: A condition in which an individual feels a compulsive need to continue taking a drug. In the process, the drug assumes an increasingly central role in the individual’s life.

Chapter 1 Drugs and Behavior today ■ 5

the drug is present in the body and later, when the drug-taking behavior stops. Drug dependence, there- fore, produces long-lasting brain changes. As Alan Lesh- ner, former director of the National Institute on Drug Abuse (NIDA), has put it, a “switch” in the brain seems to be thrown following prolonged drug use. It starts as a voluntary behavior, but once that switch is thrown, a pattern of drug dependence takes over. On a psycho- logical and sociological level, drug dependence can be viewed as the result of a complex interaction of the in- dividual and his or her environment. We cannot fully understand the problem of drug dependence without being aware of the social context in which drug-taking behavior occurs. As we will see in Chapter 17, the rec- ognition that drug dependence can be defined in terms of biological, psychological, and social components has important implications for designing effective treat- ment programs.6

Which drugs have the greatest potential for creating drug dependence? How can someone escape drug de- pendence once it is established? What factors increase or decrease the likelihood of drug-taking behavior in the first place? These are among the questions we will con- sider next, as we examine the impact of drugs and drug- taking behavior on our lives.

A Matter of Definition: What Is a Drug? Considering the ease with which we speak of drugs and drug use, it seems that it should be relatively easy to explain what we mean by the word drug. Unfortunately, there are significant problems in arriving at a clear definition.

The standard approach is to characterize a drug as a chemical substance that, when taken into the body, alters the structure or functioning of the body in some way. In doing so, we are accounting for examples such as medi- cations used for the treatment of physical disorders and mental illnesses, as well as for alcohol, nicotine, and the typical street drugs. Unfortunately, however, this broad definition could also refer to ordinary food and water. Because it does not make much sense for nutrients to be considered drugs, we need to refine our definition by adding the phrase excluding those nutrients considered to be related to normal functioning.

But we may still be on slippery ground. We can now effectively eliminate the cheese in your next pizza from being considered a drug, but what about some ex- otic ingredient in the sauce? Sugar is safely excluded, even though it has significant energizing (and therefore behavioral) effects on us, but what about the cayenne pepper that burns your tongue? Where do we draw the

line between a drug and a nondrug? It is not an easy question to answer.

We can learn two major lessons from this seem- ingly simple task of defining a drug. First, there is prob- ably no perfect definition that would distinguish drugs from nondrugs without leaving a number of cases that fall within some kind of gray area. The best we can do is to set up a definition, as we have, that handles most of the substances we are likely to encounter. However, significant practical difficulties may still arise. As we will see in Chapter 14, the fact that dietary supplements are currently not regulated in the United States has resulted from a governmental decision that these particular substances are not to be considered drugs in the same category as prescription or nonprescription (over-the- counter) medications. Whether or not this distinction is an arbitrary one continues to be a matter of debate.

The second lesson is more subtle. We often draw the distinction between drugs and nondrugs not in terms of their physical characteristics but, rather, in terms of whether the substance in question has been intended to be used primarily as a way of inducing a bodily or psychological change.7 By this reasoning, if the pizza maker intended to put that spice in the pizza to make it taste better, the spice might not be considered a drug; it would simply be another ingredient in the recipe. If the pizza maker intended the spice to intoxicate you or quicken your heart rate, then it might be considered a drug (See Health Line on page 6).

Ultimately, the problem is that we are trying to reach a consensus on a definition that fits our intuitive sense of what constitutes a drug. We may find it difficult to de- fine pornography, but (as has been said in the halls of the U.S. Supreme Court) we know it when we see it. So it may be with drugs. Whether we realize it or not, when we discuss the topic of drugs, we are operating within a context of social and cultural values, a group of shared feelings about what kind of behavior (that is, what kind of drug-taking behavior) is right and what kind is wrong.

The judgments we make about drug-taking behav- ior even influence the terminology we use when refer- ring to that behavior. When we say “drug misuse” and “drug abuse,” for example, we are implying that some- thing wrong is happening, that a drug is producing some harm to the physical health or psychological well-being of the drug user or to society in general.

drug: A chemical substance that, when taken into the body, alters the structure or functioning of the body in some way, excluding those nutrients consid- ered to be related to normal functioning.

6 ■ Part One Drugs in Society/Drugs in Our Lives

But by what criteria do we say that a drug is being misused or abused? We cannot judge on the basis of whether the drug is legal or illegal, since decisions about the legality of a psychoactive drug are more often made as a result of historical and cultural circumstances than on the physical properties of the drug itself. Tobacco, for example, has deeply rooted associations in American history, dating to the earliest colonial days. Although it is objectionable to many individuals and harmful to the health of the smoker and others, tobacco is nonetheless a legal commodity, although its commercial availability is limited to adults. Alcohol is another legal commodity, available within the bounds of the law, even though it can be harmful to individuals who become inebriated and to others who may be affected by the drinker’s drunken be- havior. The difficulty of using a criterion based on legality is further complicated by differences in religious attitudes toward these substances in some societies in the world.

Instrumental Drug Use/ Recreational Drug Use It is useful to base our discussion about drug abuse and misuse by answering a simple but fundamental ques- tion: What is the intent or motivation of the drug user with respect to this kind of behavior? In terms of the in- tent of the individual, drug-taking behavior can be clas- sified as either instrumental or recreational.8

By instrumental use, we mean that a person is tak- ing a drug with a specific socially approved goal in mind. The user may want to stay awake longer, fall asleep more quickly, or recover from an illness. If you are a medi- cal professional on call over a long period of time or a

Health Line Defining Drugs: Olive Oil, Curry Powder, and a Little Grapefruit?

An ever-increasing number of reminders about the blurri- ness of the distinction between drugs and nondrugs come from research on the chemical properties of specific foods we eat on a daily basis. For example, in 2005 it was found that freshly pressed olive oil contains large amounts of oleocanthal, a compound that inhibits the activity of cy- clooxygenase enzymes in exactly the same way as ibupro- fen, a popular nonsteroidal anti-inflammatory medication (see Chapter 14). Essentially, olive oil reduces inflamma- tion in the body in a drug-like manner. By this definition, olive oil could be classified as a drug.

This discovery provides a biochemical clue to under- standing the well-documented but puzzling health benefits of a Mediterranean (olive oil-based) diet, which leads to a lower risk of cancer, heart disease, and other chronic disor- ders, despite its heavy emphasis on fat and salt. This particu- lar diet may also lower the risk of clinical depression.

Another example is the spice turmeric, used com- monly in most commercial curry powders, as well as add- ing the bright yellow color in many mustards. The active ingredient of turmeric, called curcumin, has been credited with several medicinal benefits. Curcumin apparently has antioxidant, anti-inflammatory, antiviral, antibacte- rial, and antifungal properties with potential benefits in the treatment of cancer, diabetes, arthritis, Alzheimer’s disease, and other chronic disorders. In 2005 alone, nearly 300 technical and scientific papers cited the drug-like activ- ity of curcumin—three times the number reported in 2000. If the regulatory hurdles established by the U.S. Food and

Drug Administration with respect to long-term safety can be overcome, curcumin could provide an inexpensive alterna- tive to several currently available prescription drugs.

Still another example is grapefruit. A common flavo- noid called naringenin, found in grapefruit, has a specific inhibitory effect on the secretion of hepatitis C virus from infected liver cells. Nontoxic amounts of naringenin reduced hepatitis C virus secretion by as much as 80 per- cent. People taking certain prescription medications have to be careful if they are eating grapefruit at the same time. The interaction effects will be covered in Chapter 3.

As we continue to learn more about the therapeutic or drug-interacting effects of common foods and spices, the customary exclusion of nutrients in the definition of drugs becomes increasingly problematic. In the future, we might be hearing people say that they are taking olive oil, curry powder, or a little grapefruit extract for “medicinal reasons.”

Sources: Beauchamp, G. K.; Keast, R. S. J.; More, D.; Lin, J.; Pika, J.; Han, Q.; Lee, C. H.; Smith, A. B.; and Breslin, P. A. S. (2005). Phytochemistry: Ibuprofen-like activity in extra- virgin olive oil. Nature, 437, 45–46. Hampton, Tracy (2008, April 2). Grapefruit compound battles hepatitis C. Journal of the American Medical Association, 1532. Sanchez-Ville- gas, A.; Delgado-Rodriguez, M.; Alonso, A.; Schlatter, J., et al. Association of the Mediterranean dietary pattern with the incidence of depression. Archives of General Psychia- try, 66, 1090–1098. Stix, G. (2007, February). Spice healer. Scientific American, pp. 66–69.

instrumental use: Referring to the motivation of a drug user who takes the drug for a specific purpose other than getting “high.”

Chapter 1 Drugs and Behavior today ■ 7

long-distance truck driver, your taking a drug with the goal of staying alert is considered acceptable by most people. Recovering from an illness and achieving some reduction in pain are goals that are unquestioned. In these cases, drug-taking behavior occurs as a means toward an end that has been defined by our society as legitimate.

The legal status of the drug itself or whether we agree with the reason for the drug-taking behavior is not the is- sue here. The instrumental use of drugs can involve pre- scription and nonprescription, or over-the-counter, drugs that are licitly obtained and taken for a particular medical purpose. Examples include an antidepressant prescribed for depression, a cold remedy for a cold, an anticonvulsant drug to control epileptic seizures, and insulin to maintain the health of a person with diabetes. But the instrumental use of drugs can also involve drugs that are illicitly obtained, such as an amphetamine or other stimulant drug that has been procured by illegal means to help a person stay awake and alert after hours without sleep.

In contrast, recreational use means that a person is taking the drug not as a means to a socially approved goal but for the purposes of experiencing the effect of the drug itself. The motivation is to enjoy a pleasur- able feeling or positive state of mind. Whatever happens as a consequence of recreational drug-taking behavior is viewed not as a means to an end, but as an end onto itself. Drinking alcohol and smoking tobacco are two examples of licit recreational drug-taking behavior.

Involvement with street drugs, in the sense that the goal is to alter one’s mood or state of consciousness, falls into the category of illicit recreational drug-taking behavior.

Although this four-group classification scheme, as shown in Figure 1.2, can help us in understanding the complex relationship between drugs and behavior, there will be instances in which the category is less than clear. Drinking an alcoholic beverage, for example, is considered recreational drug-taking behavior under most circum- stances. If it is recommended by a physician for a speci- fied therapeutic or preventive purpose (see Chapter 8), however, the drinking might be considered instrumental in nature. Thus, whether drug use is judged to be recre- ational or instrumental is determined in no small part by the circumstances under which the behavior takes place.

Drug Misuse or Drug Abuse? How do the terms drug misuse and drug abuse, fit into this scheme? Drug misuse typically applies to cases in which

F i g u r e 1 . 2

Four categories of drug-taking behavior, derived from combinations of the user’s goal and the drug’s legal status.

Source: Adapted from Goode, E. (2008). Drugs in American Society (7th ed.). New York: McGraw-Hill, p. 14.

Taking Valium with a prescription to relieve anxiety

Taking No Doz to stay awake on a long trip

Taking amphetamines without a prescription to stay awake the night before a test

Taking morphine without a prescription to relieve pain

Having an alcoholic drink to relax before dinner

Smoking a cigarette or a cigar for enjoyment

Smoking marijuana to get high

Taking LSD for the hallucinogenic effects

Licit Illicit

Instrumental Use

Recreational Use

Legal Status

Goal

recreational use: Referring to the motivation of a drug user who takes the drug only to get “high” or achieve some pleasurable effect.

drug misuse: Drug-taking behavior in which a prescrip- tion or over-the-counter drug is used inappropriately.

drug abuse: Drug-taking behavior resulting in some form of physical, mental, or social impairment.

8 ■ Part One Drugs in Society/Drugs in Our Lives

a legal prescription or over-the-counter (OTC) medication is used inappropriately. Many instances of drug misuse in- volve instrumental goals. For example, drug doses may be increased beyond the level of the prescription in the mis- taken idea that if a little is good, more is even better. Or doses may be decreased from the level of the prescription to make the drug supply last longer. Drugs may be contin- ued longer than they were intended to be used; they may be combined with some other drug; or a prescription drug

may (in violation of instructions) be shared by family mem- bers or given to a friend.

Drug misuse can be dangerous and potentially lethal, particularly when alcohol is combined with drugs that depress the nervous system. Drugs that have this particu- lar feature include antihistamines, antianxiety drugs, and sleeping medications. Even when alcohol is not involved, however, drug combinations can still represent serious health risks, particularly for the elderly, who often take a

Drugs . . . in Focus

Drug Abuse and the College Student: An Assessment Tool In a research study conducted at Rutgers University, a cutoff score of five or more “yes” responses to the following twenty- five questions in the Rutgers Collegiate Substance Abuse Screening Test (RCSAST) was found effective in correctly classifying 94 percent of young adults in a clinical sample as problem users and 89 percent of control individuals as nonproblem users. It is important, however, to remember that the RCSAST does not by itself determine the presence of sub- stance abuse or dependence (see Chapter 2). The RCSAST is designed to be used as one part of a larger assessment battery aimed at identifying which young adults experience problems due to substance use and specifically what types of problems a particular individual is experiencing. Here are the questions:

1. Have you gotten into financial trouble as a result of drinking or other drug use?

2. Is alcohol or other drug use making your college life unhappy?

3. Do you use alcohol or other drugs because you are shy with other people?

4. Has drinking alcohol or using other drugs ever caused conflicts with close friends of the opposite sex?

5. Has drinking alcohol or using other drugs ever caused conflicts with close friends of the same sex?

6. Has drinking alcohol or using other drugs ever dam- aged other friendships?

7. Has drinking alcohol or using other drugs ever been behind your losing a job (or the direct reason for it)?

8. Do you lose time from school due to drinking and/or other drug use?

9. Has drinking alcohol or using other drugs ever inter- fered with your preparations for exams?

10. Has your efficiency decreased since drinking and/or using other drugs?

11. Do you drink alcohol or use other drugs to escape from worries or troubles?

12. Is your drinking and/or using other drugs jeopardizing your academic performance?

13. Do you drink or use other drugs to build up your self-confidence?

14. Has your ambition decreased since drinking and/or drug using?

15. Does drinking or using other drugs cause you to have difficulty sleeping?

16. Have you ever felt remorse after drinking and/or using other drugs?

17. Do you drink or use drugs alone? 18. Do you crave a drink or other drug at a definite time daily? 19. Do you want a drink or other drug the next morning? 20. Have you ever had a complete or partial loss of mem-

ory as a result of drinking or using other drugs? 21. Is drinking or using other drugs affecting your reputation? 22. Does your drinking and/or using other drugs make you

careless of your family’s welfare? 23. Do you seek out drinking/drugging companions and

drinking/drugging environments? 24. Has your physician ever treated you for drinking and/

or other drug use? 25. Have you ever been to a hospital or institution on

account of drinking or other drug use?

Source: Bennett, M. E.; McCrady, B. S.; Frankenstein, W.; Laitman, L. A.; Van Horn, D. H. A.; and Keller, D. S. (1993). Identifying young adult substance abusers: The Rutgers Collegiate Substance Abuse Screening Test. Journal of Studies in Alcohol, 54, 522–527. Reprinted with permission of the authors of the RCSAST.

Chapter 1 Drugs and Behavior today ■ 9

large number of separate medications. This population is especially vulnerable to the hazards of drug misuse.

In contrast, drug abuse is typically applied to cases in which a licit or illicit drug is used in ways that produce some form of physical, mental, or social impairment (See Drug in Focus on p. 8). The primary motivation for individuals involved in drug abuse is recreational. Drugs with abuse potential include not only the common street drugs but also legally available psychoactive substances, such as caffeine and nicotine (stimulants), alcohol and inhaled solvents (depressants), and a number of pre- scription or OTC medications designated for medical purposes but used by some individuals exclusively on a recreational basis. In Chapter 5, we will examine con- cerns about the abuse of opioid pain medications such as Vicodin, OxyContin, and Percocet, among others. In these particular cases, the distinction between drug mis- use and drug abuse is particularly blurry. When there is no intent to make a value judgment about the motiva- tion or consequences of a particular type of drug-taking behavior, we will refer to the behavior simply as drug use.

Before examining the major role that drugs and drug-taking behavior play in our lives today, however, it is important to examine the historical foundations of drug use. We need to understand why drug-taking behavior has been so pervasive over the many centuries of human history, and why drug-taking behavior remains so compel- ling for us in our contemporary society. We also need to understand the ways in which our society has responded to problems associated with drug use. How have our at- titudes toward drugs changed over time? How did people feel about drugs and drug-taking behavior one hundred years ago, fifty years ago, twenty years ago, or even ten years ago? These are questions that we will now address.

Drugs in Early Times

Try to imagine the accidental circumstances under which a psychoactive drug might have been discovered. Thousands of years ago, perhaps a hundred thousand years ago, the process of discovery would have been as natural as eating, and the motivation as basic as sim- ple curiosity. In cool climates, next to a cave dwelling may have grown a profusion of blue morning glories or brightly colored mushrooms, plants that produce hal- lucinogens similar to LSD. In desert regions, yellow- orange fruits grew on certain cacti, the source of the hallucinogenic drug peyote. Elsewhere, poppy plants, the source of opium, covered acres of open fields. Coca leaves, from which cocaine is made, grew on shrubs along the mountain valleys throughout Central and

South America. The hardy cannabis plant, the source of marijuana, grew practically everywhere.

Some of this curiosity may have been sparked by observing the unusual behavior of animals as they fed on these plants. Within their own experience, people made the connection, somewhere along the line, be- tween the chewing of willow bark (the source of mod- ern-day aspirin) and the relief of a headache or between the eating of the senna plant (a natural laxative) and the relief of constipation.9

Of course, some of these plants made people sick, and many of them were poisonous and caused death. However, it is likely that the plants that had the strang- est impact on humans were the ones that produced hallucinations. Having a sudden vision of something totally alien to everyday life must have been overwhelm- ing, like a visit to another world. Individuals with prior knowledge about such plants, as well as about plants with therapeutic powers, would eventually acquire great power over others in the community.

The accumulation of knowledge about conscious- ness-altering substances would mark the beginning of shamanism, a practice among primitive societies, dat- ing back by some estimates more than forty thousand

In a wide range of world cultures throughout history, halluci- nogens have been regarded as having deeply spiritual pow- ers. Under the influence of drugs, this modern-day shaman communicates with the spirit world.

shamanism: The philosophy and practice of healing in which diagnosis or treatment is based on trancelike states, on the part of either the healer (shaman) or the patient.

10 ■ Part One Drugs in Society/Drugs in Our Lives

years, in which an individual called a shaman acts as a healer through a combination of trances and plant- based medicines, usually in the context of a local reli- gious rite. Shamans still function today in remote areas of the world, often alongside practitioners of modern medicine. As we will see in Chapter 6, hallucination- producing plants of various kinds play a major role in present-day shamanic healing.

With the development of centralized religions in Egyptian and Babylonian societies, the influence of sha- manism gradually declined. The power to heal through one’s knowledge of drugs passed into the hands of the priesthood, which placed greater emphasis on formal rituals and rules than on hallucinations and trances.

The most dramatic testament to the development of priestly healing during this period is a 65-foot-long Egyptian scroll known as the Ebers Papyrus, named after a British Egyptologist who acquired it in 1872. This mammoth document, dating from 1500 b.c., contains more than eight hundred prescriptions for practically every ailment imaginable, including simple wasp stings and crocodile bites, baldness, constipation, headaches, enlarged prostate glands, sweaty feet, arthritis, inflamma- tions of all types, heart disease, and cancer. More than a hundred of the preparations contained castor oil as a natural laxative; some contained “the berry of the poppy,” which we now recognize as the Egyptian reference to opium. Other ingredients were quite bizarre: lizard’s blood, the teeth of swine, the oil of worms, the hoof of an ass, putrid meat with fly specks, and crocodile dung (excrement of all types being highly favored for its ability to frighten off the evil spirits of disease).10

How successful were these strange remedies? It is impossible to know because no records were kept on what happened to the patients. Although some of the ingredients (such as opium and castor oil) had true medicinal value, much of the improvement from these concoctions may have been psychological rather than physiological. In other words, improvements in the pa- tient’s condition resulted from the patient’s belief that he or she would be helped—a phenomenon known as the placebo effect. Psychological factors have played a critical role throughout the history of drugs. The impor- tance of the placebo effect as an explanation of some drug effects will be examined in Chapter 3.

Along with substances that had genuine healing properties, some psychoactive drugs were put to less posi- tive use. In the early Middle Ages, Viking warriors ate the mushroom Amanita muscaria, known as fly agaric, and experienced a tremendous increase in energy, which resulted in wild behavior in battle. They were called Ber- serkers because of the bear skins they wore, but this is

the origin of the word “berserk” as a reference to reckless and violent behavior. At about the same time, witches operating on the periphery of European society created “witch’s brews,” mixtures made of various plants such as mandrake, henbane, and belladonna, creating strange hallucinations and a sensation of flying. The toads that they included in their recipes didn’t hurt either: We know now that the sweat glands of certain toads contain a chemical related to dimethyltryptamine (DMT), a powerful hallucinogenic drug (see Chapter 6).11

Drugs in the Nineteenth Century

By the end of the nineteenth century, the medical profes- sion had made significant strides with respect to medicinal healing. Morphine was identified as the active ingredient in opium, a drug that had been in use for at least three thousand years and had become the physician’s most reli- able prescription for the control of pain due to disease and injury. The invention of the syringe made it possible to deliver the morphine directly and speedily into the blood- stream. Cocaine, having been extracted from coca leaves, was used as a stimulant and antidepressant. Sedative pow- ers to calm the mind or induce sleep had been discovered in bromides and chloral hydrate.

There were also new drugs for specific purposes or particular diseases. Anesthetic drugs were discovered that made surgery painless for the first time in history. Some diseases could actually be prevented through the administration of vaccines, such as the vaccine against smallpox introduced by Edward Jenner in 1796 and the vaccine against rabies introduced by Louis Pasteur in 1885. The discovery of new pharmaceutical products marked the modern era in the history of healing.12

The social picture of drug-taking behavior dur- ing this time, however, was more complicated. By the 1890s, prominent leaders in the medical profession and social reformers had begun to call attention to societal problems resulting from the widespread and uncon- trolled access to psychoactive drugs. Remedies called

shaman (SHAH-men): A healer whose diagnosis or treatment of patients is based at least in part on trances. These trances are frequently induced by hallucinogenic drugs.

ebers Papyrus: An Egyptian document, dated approxi- mately 1500 b.c., containing more than eight hundred prescriptions for common ailments and diseases.

placebo (pla-Cee-bo) effect: Any change in a per- son’s condition after taking a drug, based solely on that person’s beliefs about the drug rather than on any physi- cal effects of the drug.

Chapter 1 Drugs and Behavior today ■ 11

patent medicines, sold through advertisements, ped- dlers, or general stores, contained opium, alcohol, and cocaine and were promoted as answers to virtually all common medical and nonmedical complaints.

Opium itself was cheap, easily available, and com- pletely legal. Most people, from newborn infants to the elderly, in the United States and Europe “took opium” during their lives. The way in which they took it, how- ever, was a critical social factor. The respectable way was to drink it, usually in a liquid form called laudanum. By contrast, the smoking of opium, as introduced by Chi- nese immigrants imported for manual labor in the Amer- ican West, was considered degrading and immoral. Laws prohibiting opium smoking began to be enacted in 1875. In light of the tolerant attitude toward opium drinking, the strong emotional opposition to opium smoking may be viewed as more anti-Chinese than anti-opium.13

Like opium, cocaine was in widespread use and was taken quite casually in a variety of forms during this pe- riod. The original formula for Coca-Cola, as the name suggests, contained cocaine until 1903 (see Chapter 4), as did Dr. Agnew’s Catarrh Powder, a popular remedy for chest colds. In the mid-1880s, Parke, Davis, and Company (since 2002, merged with Pfizer, Inc.) was selling cocaine and its botanical source, coca, in more than a dozen forms, including coca-leaf cigarettes and cigars, cocaine inhal- ants, a coca cordial, and an injectable cocaine solution.14

A Viennese doctor named Sigmund Freud, who was later to gain a greater reputation for his psychoana- lytic theories than for his ideas concerning psychoactive drugs, promoted cocaine as a “magical drug.” In an in- fluential paper published in 1884, Freud recommended cocaine as a safe and effective treatment for morphine addiction. When a friend and colleague became heavily

addicted to cocaine, Freud quickly reversed his position, regretting for the rest of his life that he had been initially so enthusiastic in recommending its use (see Chapter 4).15

Drugs and Behavior in the Twentieth Century

By 1900, the promise of medical advances in the area of drugs was beginning to be matched by concern about the dependence that some of these drugs could pro- duce. For a short while after its introduction in 1898, heroin (a derivative of morphine) was completely legal and considered safe. Physicians were impressed with its effectiveness in the treatment of coughs, chest pains, and the respiratory difficulties associated with pneumo- nia and tuberculosis. This was an era in which antibiotic drugs were unavailable, and pneumonia and tuberculo- sis were among the leading causes of death.16

Some physicians even recommended heroin as a treatment for morphine addiction. Its powerful addictive properties, however, soon became evident. The enactment of laws restricting access to heroin and certain other psy- choactive drugs, including marijuana, would eventually follow in later years, a topic discussed further in Chapter 2.

At the beginning of the twentieth century, neither the general public nor the government considered al- cohol a drug. Nonetheless, the American temperance movement dedicated to the prohibition of alcohol con- sumption, led by the Women’s Christian Temperance Union and the Anti-Saloon League, was a formidable political force. In 1920, the Eighteenth Amendment to the U.S. Constitution took effect, ushering in the era of national Prohibition, which lasted for thirteen years.

Although successful in substantially reducing the rates of alcohol consumption in the United States, as well as the number of deaths from alcohol-related dis- eases, Prohibition also succeeded in establishing a na- tionwide alcohol distribution network dominated by sophisticated criminal organizations.17 Violent gang wars arose in major American cities as one group battled another for control of the liquor trade.

By the early 1930s, whatever desirable health- related effects Prohibition may have brought were per- ceived to be overshadowed by the undesirable social changes that had come along with it. Since its end in 1933, the social problems associated with the era

Around 1900, heroin was advertised as a completely safe rem- edy for common ailments, along with aspirin. No one knows how many people became dependent on heroin as a result.

patent medicine: Historically, a drug or combination of drugs sold through peddlers, shops, or mail-order advertisements.

12 ■ Part One Drugs in Society/Drugs in Our Lives

of Prohibition have often been cited as an argument against the continuing restriction of psychoactive drugs in general.

Drugs and Behavior from 1945 to 1960 In the years following World War II, for the first time, physicians were able to control bacteria-borne infectious diseases through the administration of antibiotic drugs. Al- though penicillin had been discovered in a particular spe- cies of mold by Alexander Fleming in 1928, techniques for extracting large amounts from the mold were not perfected until the 1940s. Also during that time, Selman Waksman found that a species of fungus had powerful antibacterial effects; it was later to be the source of the drug streptomycin.

In the field of psychiatry, advances in therapeutic drugs did not occur until the early 1950s, when quite ac- cidentally a group of psychoactive drugs were discovered that relieved schizophrenic symptoms without producing heavy sedation. The first of these, chlorpromazine (brand name: Thorazine), reduced the hallucinations, agitation, and disordered thinking common to schizophrenia. Soon after, there was a torrent of new drugs, forming the basis not only for the treatment of schizophrenia but also the

treatment of mental illness in general. It was a revolution in psychiatric care, equivalent to the impact of antibiotics in medical care a decade earlier.

In the recreational drug scene of post–World War II America, a number of features stand out. Smoking was considered romantic and sexy, and smoking was common- place. In 1955, regular cigarette smoking involved more than half of all male adults and more than one-quarter of all female adults in the United States. It was the era of the two-martini lunch; social drinking was at the height of its popularity and acceptance. Cocktail parties dominated the social scene. There was little or no public awareness that alcohol or tobacco use constituted drug-taking behav- ior. In contrast, the general perception of certain drugs such as heroin, marijuana, and cocaine was simple and negative: They were considered bad, they were illegal, and “no one you knew” had anything to do with them. Illicit drugs were seen as the province of criminals, the urban poor, and nonwhites.18 The point is that an entire class of drugs were, during this period, outside the mainstream of American life. Furthermore, an atmosphere of fear and suspicion surrounded people who took such drugs. None- theless, for the vast majority of Americans, drugs were not considered an issue in their lives.

Drugs and Behavior after 1960 During the 1960s, basic premises of American life—the beliefs that working hard and living a good life would

The famous Woodstock Festival concert drew an estimated 500,000 people to a farm in upstate New York in the summer of 1969. According to historian David Musto, the peaceful- ness of such a gigantic gathering is considered to have been due, at least in part, to the widespread use of marijuana, as opposed to alcohol.

chlorpromazine (chlor-PrO-mah-zeen): An antipsy- chotic (antischizophrenia) drug. Brand name is Thorazine (THOR-a-zeen).

Chapter 1 Drugs and Behavior today ■ 13

bring happiness and that society was stable and calm— were being undermined by disturbing events: President John F. Kennedy was assassinated in 1963; Dr. Martin Luther King Jr. and Senator Robert Kennedy were gunned down in 1968. We worried about the continuing Cold War, nuclear annihilation, and Vietnam.

College students, in particular, found it difficult to be as optimistic about the future as their parents had been. To many of them, the reality of the Vietnam War represented all that had gone wrong with the previous generation.19 At the same time, many young people were searching for new answers to old problems, and their search led to experimentation with drugs that their par- ents had been taught to fear. The principal symbol of this era of defiance against the established order, and indeed against anyone over thirty years old, was marijuana.

No longer would marijuana be something foreign to middle-class America. Along with other drugs such as LSD, stimulants (“uppers”), and depressants (“downers”), marijuana became part of the lives of sons and daugh- ters in our own families and in our own neighborhoods. Adding to the turbulence of this period was a disturbing increase in heroin abuse across the country. The issues surrounding drug abuse, once a problem associated with minority populations, inner cities, and the poor, were now too close to our personal lives for most of us to ignore.

One of the governmental responses to these events, particularly the increase in heroin dependence, was to fi- nance basic research related to the effects of drugs on the brain. The timing could not have been better because during the 1970s, a new branch of science, called neuro- science, was being established. Its intent was to bring to- gether researchers from formerly separate scientific fields in a new collaborative effort to understand the relation- ship between brain functioning and human behavior. In the area of drug research, pharmacologists (those who specialize in the study of drugs) were joined by biochem- ists, psychologists, and psychiatrists, among others. One of the important discoveries that emerged from this era was the identification of receptors in the brain that are tailored specifically for drugs taken into the body. The findings of neuroscience research will be discussed in Chapter 3 and in several of the chapters that follow.

With the decade of the 1980s, however, came signifi- cant changes in the mood of the country, dominated by a reaction to the social and political attitudes of earlier de- cades. The focus of media attention was on the image of the “yuppie,” a young, upwardly mobile professional. The political climate grew more conservative in all age groups. In the area of drugs, concerns about heroin dependence were being overshadowed by a new fixation on cocaine. At first, cocaine took on an aura of glamor, and (because it was so expensive) cocaine became a symbol of material

success. The media spotlight shone on a steady stream of celebrities in entertainment and sports who used cocaine. Not long after, however, the very same celebrities who had accepted cocaine into their lives were experiencing the dark consequences; many were in rehabilitation pro- grams, and some had died from cocaine overdoses.

To make matters worse, a smokable and cheap form of cocaine called crack succeeded in extending the problems of cocaine dependence to the inner cities of the United States, to segments of American society

neuroscience: The scientific study of the nervous system, undertaken as a collaborative effort among researchers from many scientific disciplines.

Quick Concept Check 1.1

Understanding the History of Drugs and Behavior Check your understanding of the changes in drug-taking behavior over history by matching the statement (on the left) with the appropriate historical period (on the right).

1. Opium and castor oil are first documented as therapeutic drugs.

2. Marijuana use symbolizes a generation’s defiance of establishment values.

3. Waksman discovers the antibacterial effects of streptomycin.

4. Opium use extends to all levels of Western society.

5. Cocaine use is at its peak as a symbol of glamor and material success.

6. Heroin is first introduced as a treatment for morphine addiction.

7. Widespread use of antischizo- phrenic drugs in mental hospitals begins.

8. Vaccines against smallpox and rabies are introduced.

a. approximately 1500 b.c.

b. late 1700s to late 1880s

c. late 1800s

d. late 1940s

e. mid-1950s

f. late 1960s to early 1970s

g. early 1980s

Answers: 1. a 2. f 3. d 4. b 5. g 6. c 7. e 8. b

14 ■ Part One Drugs in Society/Drugs in Our Lives

that did not have the financial resources to afford co- caine itself. In the glare of intense media attention, crack dependence soon took on all the aspects of a national nightmare. Fortunately, by the end of the 1990s, the extent of crack abuse had greatly dimin- ished, and the urban violence and social upheaval as- sociated with it had declined. Nonetheless, the legacy of this era continues to be felt to the present day.20

Present-Day Attitudes Toward Drugs

Attitudes toward drug-taking behavior in the twenty-first century are quite different from those that prevailed at an earlier time. First, there is a far greater awareness today that a wide range of psychoactive drugs, whether they are licit or illicit, qualify as substances with varying levels of potential for misuse and abuse. The “war on drugs,” in America, declared officially in 1971 and still ongoing today, is no longer a war on a particular drug, such as heroin in the 1970s or cocaine in the 1980s. We are now fully aware of the widespread personal and social diffi- culties created by the abuse of alcohol, steroids, inhal- ants, and nicotine, as well as the misuse of prescription pain medications, prescription stimulants, and over-the- counter medications of all kinds. In short, the battles be- ing waged today are against a wide range of drug misuse and abuse, involving licit as well as illicit substances.

A second difference in attitudes toward drug-taking behavior is related to the history of such behavior in our society since the late 1960s. It is important to recognize that in 1980, about two-thirds of high school seniors had reported illicit drug use (principally marijuana smoking) at some time in their lives. They were born toward the end of the “baby boom” generation (technically defined as those born between 1946 and 1964) and were the first group to have grown up during the explosion of drug experimenta- tion. Now, as the parents of teenagers in the twenty-first century, they face the challenge of dealing with the pres- ent-day drug-taking behavior of their children.

What has been the effect, if any, on drug-taking be- havior among children of parents who were involved in drug use at an earlier time? With respect to marijuana use, studies have resulted in two major conclusions. First, parents of this particular generation have a more accept- ing attitude of drug use than an older generation and are more resigned to the idea that their own children would engage in illicit drug-taking behavior. Second, there is no evidence that the prior use of marijuana by parents is related to the extent of present marijuana use by their

children. Indeed, the far stronger association lies between adolescent marijuana use and the adolescent’s own per- sonal attitude toward the lack of harm involved.21

Patterns of Drug Use in the United States

How is it possible to obtain information that would give us a statistical picture of drug-taking behavior today? Assuming that we cannot conduct large-scale random drug testing, the only alternative we have is simply to ask people about their drug-taking behavior through self-reports. We encourage honesty and arrange the data-collection procedure so as to convince the respon- dents that their answers are confidential, but the fact remains that any questionnaire is inherently imperfect because there is no way to verify the truthfulness of what people say about themselves. Nevertheless, ques- tionnaires are all we have, and the statistics on drug use are based on such survey measures.

One of the best-known surveys, referred to as the Monitoring the Future study, has been conducted by the University of Michigan every year since 1975. Typi- cally, nearly fifty thousand American students in the eighth, tenth, and twelfth grades participate in a nation- ally representative sampling each year, as well as more than seven thousand American college students and adults between nineteen and fifty years old.

The advantage of repeating the survey with a new sample year after year is that it enables us to examine trends in drug-taking behavior over time and compare the use of one drug relative to another over the years. We can assume that the degree of overreporting and un- derreporting stays relatively constant over the years and does not affect interpretation of the general trends.

Survey questions concerning drug use have been phrased in four basic ways:

■ Whether an individual has ever used a certain drug in his or her lifetime. The percentage of those saying “yes” is referred to as the lifetime prevalence rate.

■ Whether an individual has used a certain drug over the past year. The percentage of those saying “yes” is referred to as the annual prevalence rate.

■ Whether an individual has used a certain drug within the past thirty days. The percentage of those saying “yes” is referred to as the past-month prevalence rate.

■ Whether an individual has used a certain drug on a daily basis during the previous thirty days. The per- centage of those saying “yes” is referred to as the daily prevalence rate.

Chapter 1 Drugs and Behavior today ■ 15

You can see that these questions distinguish three important degrees of involvement with a given drug. The first question focuses on the extent of experimenta- tion, including individuals who may have taken a drug only once or twice in their lives but may have stayed away from it ever since. The second and third questions focus on the extent of current but moderate drug use, and the fourth question focuses on the extent of heavy drug use. What do the numbers tell us?

Illicit Drug Use among High School Seniors Understanding the present-day drug-taking behavior among U.S. high school seniors is not an easy task. In order to see the total picture, we have to look to the past as well as the present, and make some educated guesses as to the future based on current trends.

As seen in Figure 1.3, it has been something of a roller-coaster ride since the Michigan survey began in 1975. The early statistics were indeed scary. By the end of the 1970s, prevalence rates for illicit drug use had reached historically high levels. About one-half of high

school seniors reported smoking marijuana or using an illicit drug of some kind in the past year. At that time and continuing into the mid-1980s, 12 percent (one in eight seniors) reported using cocaine or crack cocaine in the past year. Fortunately, annual prevalence rates for illicit drug use among high school seniors showed a steep decline through the 1980s, ending at a historically low level (27 percent) around 1992. But at that point, a dramatic reversal occurred. Prevalence rates took a sharp upward turn during the decade of the 1990s. From 2000 to most recent figures in 2011, rates have been fairly steady at around 38 to 40 percent. The bot- tom line is that, in terms of illicit drug use in this demo- graphic group, the present is somewhere between the worst (in 1979) and the best (in 1992).

Looking at the numbers more closely, however, we can see the current pattern of drug use among high school seniors in a somewhat different light. If we ex- amine the annual prevalence rates for the use of illicit drugs other than marijuana, the trend is down from about 20 percent in 2000 to about 18 percent in 2011.

This good news, however, is counterbalanced by a more complicated trend with respect to using marijuana

0

40

60

Year

20

Twelfth graders

Tenth graders

Eighth gradersP er

ce n

ta ge

o f

st u

d en

ts

’76 ’78 ’80 ’82 ’84 ’86 ’88 ’90 ’92 ’94 ’96 ’98 ’00 ’02 ’04 ’06 ’08 ’10 ’12

F i g u r e 1 . 3

Trends in annual prevalence of illicit drug use among eighth, tenth, and twelfth graders. Updated statistical information from the University of Michigan survey is available at the end of December of each calendar year through the web site: www.monitoringthefuture.org.

Note: There were no significant changes in 2012 with respect to the annual prevalence rate in eighth, tenth, or twelfth graders. For current information, consult the web site for the Monitoring the Future study.

Source: Johnston, L.D.; O’Malley, P.M.; Bachman, J.G.; and Schulenberg, J.E. (2012). Monitoring the Future: National Survey Results on Drug use, 1975–2011, Vol. I: Secondary School Students 2011. Ann Arbor, MI: Institute for Social Research, The University of Michigan, Table 2-2.

16 ■ Part One Drugs in Society/Drugs in Our Lives

alone. In 2000, about 37 percent of seniors reported smoking marijuana in the past year, having risen steadily through the 1990s. In the next few years, the prevalence rate declined. By 2006, however, the trend reversed itself (again). In 2011, annual marijuana use stood at 36  percent (essentially the level observed in 2000). This percentage had risen for the fourth straight year. The rate of daily marijuana smoking in 2011 stood at 6.6 percent, the highest it has been since 1981.

In other words, approximately one out of three high school seniors used marijuana over the past year and one out of sixteen seniors used marijuana daily in 2011.22

Illicit Drug Use among Eighth Graders and Tenth Graders Since 1991, the Michigan survey has collected exten- sive information about illicit drug use among students as early as the eighth grade. As Figure 1.3 shows, the up- ward trend in the percentages of annual drug use among eighth and tenth graders in the years from 1991 to 1996 parallels a similar trend among high school seniors. At the time, the data from these two groups reflected a level of drug involvement that was quite alarming. Drug-abuse professionals were left to speculate about the negative effect on still younger children, as they ob- served the drug-taking behavior of their older brothers and sisters. In general, as you would expect, changes in the trend of prevalence rates among high school seniors have been preceded, four years or so earlier, by the shift- ing prevalence rates among eighth graders.23

Illicit Drug Use among College Students According to the Michigan survey, when compared to high school seniors, college students reported in 2011 a roughly equivalent annual prevalence rate (36 percent) in the use of illicit drugs in general. As it has been the case for younger people, illicit drug use was clearly dominated by marijuana smoking. Table 1.1 shows the lifetime, annual, and 30-day prevalence rates among college students with respect to five ma- jor types of drugs: the use of marijuana, hallucinogens, and cocaine, as well as the nonmedical use of pre- scription stimulant medications and prescription pain medications.24

Alcohol Use among High School and College Students Not surprisingly, the prevalence percentages related to the use of alcohol are much higher than for illicit drugs. Whereas about 25 percent of high school seniors in 2011 reported use of illicit drugs in the past month, 40 per- cent drank an alcoholic beverage in the past month, and 22 percent reported an instance of binge drinking, defined as having five or more drinks in a row at least once in the past two weeks. These figures are at historic lows, down substantially from those found in surveys conducted in 1980, when 72 percent of high school se- niors reported that they had consumed alcohol in the past month, and 41 percent reported binge drinking.25

TAble 1.1

Percentage of five types of drug use among college students, aged 19–22

ever in liFeTime

in PAST Twelve mOnTHS

in PAST THirTy DAyS

Marijuana 46.6 33.2 19.4

Hallucinogens 6.9 4.1 0.8

Cocaine 5.5 3.3 1.2

Prescription pain medication* 12.4 6.2 2.1

Prescription stimulant medication** 13.4 9.3 4.5

*Nonmedical use of prescription pain medications include Vicodin, OxyContin, and Percocet.

**Nonmedical use of prescription stimulant medications include Adderall and Ritalin.

Note: For current information, consult the web site for the Monitoring the Future study: www.monitoringthefuture.org.

Source: Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2012). Monitoring the Future: National survey results on drug use, 1975-2011. Vol. II: College students and adults ages 19–50. Ann Arbor, MI: Institute for Social Research, The University of Michigan, Tables 2-1, 2-2, 2-3, 8-1, 8-2, and 8-3.

Chapter 1 Drugs and Behavior today ■ 17

The general decline in alcohol use and heavy drinking among adolescents from 1980 to 2011, par- ticularly since the mid-1990s, stems from a number of factors. National campaigns to reduce drunk driving, the encouragement of nondrinking designated drivers, as well as a general personal disapproval of binge drink- ing, have all played a role. An additional factor is the re- duced accessibility to alcohol for this age group; all U.S. states have now adopted a twenty-one-years-or-older requirement. While efforts to reduce underage drink- ing by enforcing restrictions of alcohol sales to minors have been credited with reducing adolescent alcohol use, however, the statistics show that more work needs to be done. In 2011, 59 percent of eighth graders found it “fairly easy” or “very easy” to obtain alcoholic bever- ages, down from 71 percent in 2000.26 About 89 percent of seniors reported the same, down from 95 percent in 2000. The drinking habits of college students, however, have shown relatively little change since the mid-1990s. In 2011, 64 percent of college students surveyed drank at least once in the previous month, and 36 percent reported an instance of binge drinking.27

Tobacco Use among High School and College Students Roughly 10 percent of high school seniors in 2011 had established a regular habit of nicotine intake by smoking at least one cigarette every day. In fact, nico- tine remains the drug most frequently used on a daily basis by high school students, although present-day rates are substantially lower than those observed when the Michigan survey began in 1975. More than twice as many high school seniors (27 percent) smoked cigarettes at that time. From the mid-1990s, there has been a steady decline in smoking rates in eighth and tenth graders as well as seniors, owing to the national attention directed toward cigarette smoking among young people. Nonetheless, in 2011, about 4 percent of seniors and 2 percent of tenth graders reported smoking at least half a pack of cigarettes per day—a strikingly high level for these age groups, considering the legal obstacles they face when attempting to ob- tain cigarettes.28

It is true that somewhat fewer college students smoke cigarettes than high school seniors, but the reason is not a matter of a change in smoking behav- ior from high school to college. It is a reflection of differences between the two populations. Non–college- bound seniors are about three times more likely than college-bound seniors to smoke at least a half pack of cigarettes per day. Therefore, the difference in smoking

rates between seniors and college students is chiefly a result of excluding the heavier smokers in the survey as students progress from secondary to postsecondary education. In 2011, about 7 percent of college students smoked cigarettes on a daily basis, with about 3 percent smoking more than half a pack per day.29

Drug Use and Drug Perceptions The decision to engage in a specific form of drug-taking behavior is intermeshed with individual perceptions about the drug in question. How risky would it be to use a particular drug? How dangerous would it be? These questions have been asked of high school seniors in the Michigan survey since 1975, and the relationship is clear. Figure 1.4 shows an almost exact “mirror-image” in the trends over more than 35 years between the per- ceived risk of harm in regular marijuana smoking and the 30-day prevalence rate.30 In the 1990s, there was a steady decline in the percentages of high school stu- dents, college students, and young adults who regarded regular drug use (regular marijuana use in particular) as potentially dangerous. These responses contrasted with reports beginning in 1978 that had shown a steady in- crease in such percentages. At the time, Lloyd Johnston, chief researcher for the Michigan survey, offered one possible reason for this reversal:

This most recent crop of youngsters [in 1996] grew up in a period in which drug use rates were down substantially from what they had been 10 to 15 years earlier. This gave youngsters less opportu- nity to learn from others’ mistakes and resulted in what I call “generational forgetting” of the hazards of drugs.31

Also troubling during much of the 1990s were changes in the way our society dealt with the potential risks of drug use. Drug abuse prevention programs in schools were scaled back or eliminated because of a lack of federal funding, parents were communicating less with their children about drug use, anti-drug public service messages were less prominent in the media than they were in the 1980s, and media coverage in this area declined. At the same time, the cultural influences of the music and entertainment industry were, at best, ambiva- lent on the question of drug-taking behavior, particularly with respect to marijuana smoking (see Chapter 7). All these elements can be seen as having contributed to the upward trend in drug use during this period.

Another question has been asked in the Michigan survey: Would you experience disapproval if you used a particular drug? Not surprisingly, the likelihood of using

18 ■ Part One Drugs in Society/Drugs in Our Lives

a drug is inversely related to how much disapproval might be experienced. This is particularly the case in the life of an adolescent, when peer approval is such an important element in guiding his or her behavior.

The two types of drug perception, the perception of possible risk or danger and the perception of disap- proval, are useful indices in predicting future trends in drug use, since shifts in perception often precede in time the observed changes in behavior. A lower level of disapproval of marijuana smoking, for example, may reflect a lower perception of riskiness, which might in turn be reflected later in an increased prevalence rate.32

Illicit Drug Use among Adults Aged Twenty-Six and Older A comprehensive report of the prevalence rates of illicit drug use among Americans in several age

groups across the life span is made possible by the National Survey on Drug Use and Health (formerly the National Household Survey on Drug Abuse). Table 1.2 shows the estimated number of illicit drug users aged twenty-six or older in the United States in 2011. About 11 percent of this population (more than 21 million people) reported using an illicit drug over the past twelve months, about 8 percent (more than 15 million people) used marijuana or hashish, and about 4 percent (more than 8 million people) engaged in the nonmedical (recreational) use of a prescription-type pain reliever, tranquilizer, stimu- lant, or sedative. As with the results of the Michigan survey, however, there are some limitations on the interpretation of these estimates. Neither patients in- stitutionalized for medical or psychiatric treatment nor homeless people are included in the collection of sample data.33

F i g u r e 1 . 4

Trends in perceived availability of marijuana, perceived risk of marijuana use, and prevalence of marijuana use in the past month for high school seniors.

Note: There were no significant changes in 2012 with respect to any of these measures. For current information, consult the web site for the Monitoring the Future study: www.monitoringthefuture.org.

Source: Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2012). Monitoring the Future: National survey results on drug use, 1975-2011, Vol. I: Secondary school students 2011. Ann Arbor, MI: Institute for Social Research, The University of Michigan, Tables 2-3, 8-3, and 9-8.

0

10

30

50

Use: % using once or more

in past 30 days (on left-hand scale)

20

40

U se

( p

er ce

n ta

ge )

R isk an

d availab

ility (p ercen

tage)

Risk: % saying great risk of

harm in regular use (on right-hand scale)

Availability: % saying fairly easy

or very easy to get (on right-hand scale)

0

20

60

100

40

80

Availability

Risk

Use

’76 ’78 ’80 ’82 ’84 ’86 ’88 ’90 ’92 ’94 ’96 ’98 ’00 ’02 ’04 ’06 ’08 ’10 ’12

Chapter 1 Drugs and Behavior today ■ 19

TAble 1.2

Illicit drug use during the past year among persons in the United States aged 26 or older in 2011

eSTimATeD numberS OF uSerS

Any illicit drug 21,484,000

Marijuana and hashish 15,632,000

Cocaine 2,064,000

Crack 490,000

Heroin 335,000

Hallucinogens 1,098,000

LSD 135,000

Ecstasy 590,000

Methamphetamine 703,000

Inhalants 540,000

Nonmedical use of any 8,542,000 psychotherapeutic medication (not including over-the-counter drugs)

Pain relievers 6,306,000

OxyContin 776,000

Antianxiety medications 3,080,000

Sedatives 314,000

Any illicit drug other than marijuana 10,422,000

Source: Substance Abuse and Mental Health Services Administration (2012). Results from the 2011 National Survey on Drug use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Administration, Tables 1.7A and 1.8A.

Quick Concept Check 1.2

Understanding Present-Day Drug Use in the United States Check your understanding of present-day drug use in the United States by marking the following statements true or false.

1. The University of Michigan survey includes a sam- pling of all seventeen- to eighteen-year-old individuals in the United States.

2. With the exception of alcohol and nicotine, the trend in drug use from the early 1980s to the present has been a steady decline.

3. Tobacco use among college students has always been greater than that of high school seniors.

4. Marijuana is more readily available and its use is more prevalent now than it was in 1979.

Answers: 1. false 2. false 3. false 4. false

Making the Decision to Use Drugs

Why do young people turn to drugs in the first place? What factors influence the drug-taking behavior that we see in all these statistics?

When high school seniors reported their personal reasons for taking drugs, the most frequently occurring responses among the classes of 1983 and 1984 were “to have a good time with my friends” (65 percent), “to exper- iment or see what it’s like” (54 percent), “to feel good or get high” (49 percent), and “to relax or relieve tension” (41 percent). These responses were similar to reasons given by the class of 1976 in earlier surveys, and there is no reason to suspect significant differences today.34

Is there any way of predicting which individuals may be inclined to take drugs and which individuals are likely to stay drug-free? One way of thinking about predicting

drug use is to consider any given person as having a cer- tain degree of vulnerability to drug-taking behavior. This vulnerability seems to be shaped by two separate groups of factors in a person’s life. The first are risk factors, which make it more likely that a person might be involved with drugs; the second are protective factors, which make it less likely that a person might be involved with drugs.

Together, risk factors and protective factors com- bine to give us some idea about the likelihood that drug- taking behavior will occur. The emphasis, however, should be on the phrase “some idea.” We still would not know for certain which individuals would use drugs and which would not. An understanding of risk factors and protective factors in general and knowledge about which factors apply to a given individual are useful pieces of information in the development of effective drug abuse prevention programs (see Chapter 16).

Specific Risk Factors Certain factors that may appear to be strong risk fac- tors for drug-taking behavior in general (socioeconomic

risk factors: Factors in an individual’s life that increase the likelihood of involvement with drugs.

protective factors: Factors in an individual’s life that decrease the likelihood of involvement with drugs and reduce the impact that any risk factor might have.

20 ■ Part One Drugs in Society/Drugs in Our Lives

Peer influence is a major factor in predicting the extent of drug-taking behavior during adolescence. It can represent either a risk factor or a protective factor for drug abuse.

TAble 1.3

Major risk factors and protective factors: Odds ratios for marijuana use over the past year among youths aged 12–17 as related to specific questions about the social context of marijuana smoking

riSk FACTOr rePreSenTATive QueSTiOn ODDS rATiO

Antisocial behavior “How many times have you gotten a serious into fight at school or at work?”

7.10

Friends’ marijuana use “How many friends would you say use marijuana?” 6.25

Perceived prevalence of marijuana use in school

“How many of the students in your grade in school would you say use marijuana?”

4.78

Individual attitudes toward marijuana use

“How would you feel [positively] about someone your age trying marijuana?”

4.47

Friends’ attitudes toward marijuana use

“How do you think your close friends would feel [positively] about your trying marijuana?”

4.37

Note: By definition, risk factors have odds ratios greater than 1. Behavior is more likely to occur if a risk factor is present, through a multiplier designated by the odds ratio. The higher the odds ratio above one, the stronger the risk factor. By definition, protec- tive factors have odds ratios less than 1. Behavior is less likely to occur if a protective factor is present, through a multiplier desig- nated by the odds ratio. The lower the odds ratio below one, the stronger the protective factor.

PrOTeCTive FACTOr rePreSenTATive QueSTiOn ODDS rATiO

Sanctions against substance use in school

“How much trouble do you think a student in your grade would be in if he or she got caught using an illegal drug?”

0.28

Parents as sources of social support

“Would you select your mother or father as a source of social support?”

0.40

Commitment to school “Do you like going to school?” 0.45

Religiosity “How many times did you attend religious services?” 0.47

Extracurricular activities “Have you participated in at least two extracurricular activities in or out of school?”

0.52

Source: Wright, D., and Pemberton, M. (2004). Risk and protective factors for adolescent drug use: Findings from the 1999 National Household Survey on Drug Use. Rockville, MD: Substance Abuse and Mental Health Services Administration, Chapter 3 and Appendix A.

status, for example) turn out to have an association that is far from simple and may depend on the particular drug under discussion. The most reliable set of risk fac- tors consists of psychosocial characteristics that reflect a tendency toward nonconformity within society. Young people who take drugs are more inclined to attend school irregularly, have poor relationships with their par- ents, or get into trouble in general. Sociologists refer to such individuals as members of a deviant subculture.35

The effects of being a participant in a socially deviant subculture are highlighted by the increased probability that an individual will display some level of drug-taking behavior. For example, the odds of youths aged twelve to seventeen using marijuana during the past year are more than six times (6.25 times, to be precise) greater among those who had at least a few close friends who tried or used marijuana than among those who did not have such friends (the second listed risk factor in Table 1.3). Note

Chapter 1 Drugs and Behavior today ■ 21

however, that in the case of marijuana use, we are speak- ing of an increased probability that it will occur, not nec- essarily a cause-and-effect relationship.

As shown in Table 1.3, other leading risk factors for marijuana use include the perceived prevalence of marijuana use by friends in and out of school and one’s own attitude and the attitude of friends toward mari- juana smoking. By contrast, economic deprivation, as measured by a household income under $20,000, fails to be a risk factor for marijuana use.36

Specific Protective Factors Protective factors provide the basis for someone to have stronger resistance against the temptations of drugs, to have a degree of resilience against engag- ing in a drug-taking life-style, despite the presence of risk factors in that person’s life.37 It is important that we not see these protective factors as simply the in- verted image, or the negation, of opposing risk factors. Rather, each group of factors operates independently of the other. One way of thinking about protective factors is to view them as a kind of insurance policy against the occurrence of some future event that you hope to avoid.38 For example, the third protec- tive factor listed in Table 1.3 shows an odds ratio of 0.45, indicating that youths aged twelve to seventeen who answer “yes” to the question “Do you like going to school?” are about one-half (0.45, to be precise) as likely to have tried or used marijuana during the past year as youths who answer “no.”

Protective factors can serve as a buffering ele- ment among even high-risk adolescents, giving them a greater degree of resilience against drug-taking be- havior and a higher resistance to drug use than they would have had otherwise. Leading protective factors include a commitment to conventionality in one form or another and a degree of social support from one’s family.

Obviously the more protective factors in our lives, the better our chances of resilience with respect to drug-related problems. In one study, pro- tective factors were examined in one thousand high- risk male and female adolescents in the seventh and eighth grades, and information was collected on their drug use later in high school. As the number of protective factors increased, the resistance of these students to drug use increased as well. With six or more such factors in their lives, as many as 56 per- cent of the high-risk adolescents showed a resis- tance to drug use three years later. In contrast, only

20 percent of the youths with three or fewer protec- tive factors were drug-free.39

Present-Day Concerns

What does the future hold with respect to psychoac- tive drugs and drug-taking behavior? One certainty is that specific drugs will continue to come into and fall out of favor. New drugs will appear on the scene, and others may reappear like ghosts from the past, some- times in new forms and involving new faces in the drug underground.40

Club Drugs A serious concern in today’s drug scene has been the popularity of so-called “club drugs,” a term that originally referred to substances ingested at all-night dance parties (“raves”), dance clubs, and bars. Today, the term designates a loosely defined category of rec- reational psychoactive drugs that are used by young people, primarily in a social setting. Examples of club drugs include MDMA (Ecstasy), GHB, ketamine, Rohypnol, methamphetamine, and LSD. When used in combination with alcohol, as they often are, these drugs carry considerably increased health risks, beyond their own individual toxicities. Because many club drugs are colorless, tasteless, and odorless, they can be slipped unobtrusively into drinks by individuals who want to intoxicate or sedate others. The potential danger of sexual assault, therefore, is a major prob- lem.41 Drugs in Focus examines the major features of these six club drugs. A more detailed discussion will follow in Chapter 4 (methamphetamine), Chapter 6 (LSD, MDMA, and ketamine), and Chapter 13 (GHB and Rohypnol).

Nonmedical Use of Prescription Pain Relievers Although present-day prevalence rates among adoles- cents and young adults for several categories of illicit drugs are much lower than rates observed in earlier years (see Figure 1.2), the incidence of nonmedi- cal (recreational) use of prescription pain relievers has risen to alarmingly high levels and has become a major social problem. In 2011, about 3.4 million young adults, aged eighteen to twenty-five years, in the United States used prescription pain relievers

22 ■ Part One Drugs in Society/Drugs in Our Lives

Drugs . . . in Focus

Facts about Club Drugs MDMA (methylenedioxymethamphetamine) • Street names: Ecstasy, XTC, X, E, Adam, Clarity,

Lover’s Speed, Hug Drug, Euphoria, M&M • Variations: MDA (methylenedioxyamphetamine),

MDEA (methylenedioxyethylamphetamine) • Forms: Tablet or capsule • Behavioral effects: Appetite suppression, excitation,

perceptual distortions • Physiological effects: Increased heart rate and blood

pressure, dehydration • Length of effect: 3 to 6 hours • Toxicity: Marked increase in body temperature; pos-

sible heart attack, stroke, or seizure (see Chapter 6)

GHB (gamma-hydroxybutyrate) • Street names: Grievous Bodily Harm, G, Liquid X, Liquid

Ecstasy, Georgia Home Boy, Goop Soup • Variations: Gamma-butyrolactone (GBL) • Forms: Clear liquid, tablet, capsule, or white powder • Behavioral effects: Intoxication, euphoria, sedation,

anxiety reduction • Physiological effects: Central nervous system depres-

sant, stimulation of growth-hormone release • Length of effect: Up to 4 hours • Toxicity: Overdoses produce drowsiness, loss of con-

sciousness, impaired breathing, coma, potential death. GHB greatly potentiates the sedative action of alcohol (see Chapter 13).

Ketamine • Street names: K, Special K, Vitamin K, Ket • Variations: None • Forms: Liquid, white powder snorted or smoked with

marijuana or tobacco, intramuscular injection • Behavioral effects: Dreamlike state of consciousness,

hallucinations • Physiological effects: Increased blood pressure, poten-

tial seizures, and coma • Length of effect: 1 hour • Toxicity: Impaired attention and memory, impaired

motor coordination, disorientation (see Chapter 6)

Rohypnol (flunitrazepam) • Street names: Roofies, Rophies, Roche, Rope,

Forget-me pill

• Variations: None • Forms: Tablet dissolvable in beverages • Behavioral effects: Sedation • Physiological effects: Decreased blood pressure, visual

disturbances, gastrointestinal disturbances • Length of effect: 8 to 12 hours • Toxicity: Anterograde amnesia (loss of memory for

events experienced under its influence). Rohypnol effects are greatly potentiated by alcohol (see Chapter 13).

Methamphetamine • Street names: Speed, Ice, Meth, Crystal, Crystal Meth,

Crank, Fire, Glass, Ice, Rock Candy • Variations: Amphetamines, with varying degrees of

similarity • Forms: Many forms; methamphetamine can be

smoked, snorted, injected, or orally ingested. • Behavioral effects: Increased alertness and energy • Physiological effects: Increased heart rate and blood

pressure, decreased appetite • Length of effect: Several hours • Toxicity: Possible heart attack or cardiovascular col-

lapse, seizures, cerebral hemorrhage, and coma (see Chapter 4)

LSD (lysergic acid diethylamide) • Street names: Acid, Boomers, Yellow Sunshines, Bar-

rels, Blotters, Cubes, Domes, Lids, Wedges • Variations: Hallucinogens, with varying degrees of

similarity • Forms: Crystalline material soluble in water • Behavioral effects: Distortions of visual perceptions,

distortions of time and space • Physiological effects: Increased heart rate and blood

pressure, sweating, tremors • Length of effect: 30 to 90 minutes, though effects might

last several hours • Toxicity: Numbness, nausea (see Chapter 6)

Sources: Brands, B.; Sproule, B.; and Marshman, J. (1998). Drugs and drug abuse: A reference text. Toronto: Addiction Research Foundation. Ricaurte, G. A., and McConn, U. D. (2005). Recognition and management of complications of new recreational drug use. Lancet, 365, 2137–2145.

Chapter 1 Drugs and Behavior today ■ 23

recreationally in the past year; about 1.2 million used them on a recreational basis during the previ- ous month.42 Hydrocodone (brand name: Vicodin), oxycodone (brand names: Percodan, Percocet), and controlled-release oxycodone (brand name: Oxy- Contin) have been the principal drugs involved (see Chapter 5).

Nonmedical Use of Prescription Stimulant Medications For decades, individuals with attention deficit disorder (ADD) have been successfully treated with a num- ber of prescription stimulant medications, principally methylphenidate (brand name: Ritalin) and a combi- nation of dextroamphetamine and levoamphetamine (brand name: Adderall). Concern has grown, however, about two principal forms of drug misuse. The first is the practice of taking these drugs at higher doses than prescribed or combining them with alcohol. The sec- ond is the practice of diverting these drugs (that is, transferring the medication of one patient for whom it is prescribed to another individual for whom it is not prescribed), either by selling them or giving them away to friends. Nonmedical use of Adderall is of special in- terest because of the high prevalence rates among col- lege students (see Chapter 4). In 2011, approximately four million (one in nine) young adults, 18 to 25 years old, reported nonmedical use of Adderall at least once in their lifetime.43

In these cases, the drug-taking behavior has been either recreational (to achieve a state of eupho- ria) or instrumental (to be able to study late into the night).

Nonmedical Use of Over-the-Counter Cough-and-Cold Medications In 2011, approximately 5 percent of high school seniors reported taking OTC cough-and-cold medications, such as Coricidin HBP Cough and Cold Tablets, Ro- bitussin products, and NyQuil, containing the cough suppressant dextromethorphan (abbreviated DXM or DM) in the past year for the purpose of getting high, a practice commonly referred to as “robo-tripping” or “skittling.” The alcohol content (up to 10 percent) in many of these products compounds the health-related problems. The easy availability of dextromethorphan

for people of all ages and the increased risk of brain damage, seizure, and death associated with high doses of dextromethorphan are matters of great concern in today’s drug scene.44

Why Drugs? If the history of drug-taking behavior teaches us any- thing, it is that there will always be an attractiveness about the drug experience, an enticement to enter into a totally different state of consciousness. For a time, they can make us feel euphoric, light-headed, relaxed, or powerful, and there is little doubt that all this feels good. There may be nonpharmacological ways of ar- riving at these states of mind, but drugs are easy and quick. Some drugs give us the feeling that we are see- ing or hearing things in a more intense way. No mat- ter whether we are young or old, rich or poor, drugs enable us to retreat from a state of stress. Some drugs permit us to feel no pain.

Unfortunately, in every generation there will be young people who seek some form of temporary release from an unhappy existence, seeking some form of rebellion against traditional values as a valida- tion of their personal journey in life. And there will be those who will use drugs to have a good time with their friends. There will be young people who are simply willing to try anything new, including drugs. Their curiosity to find out “what it’s like” brings us full circle to the earliest times in human history, when we nibbled on the plants in the field just to find out how they tasted. In the modern era, drug experi- mentation is neither a new nor a singular phenom- enon; it can involve an alcoholic drink, an inhaled solvent from some household product, a cigarette, or an illicit drug.

As we will see in Chapter 3, drug experimenta- tion has everything to do with neural circuitry deep in our brains and the release of a neurotransmitter called dopamine, a neurochemical that is at the heart of our feelings of pleasure and reward. Release of dopamine at crucial moments is like a bold-face signal that “this event is worth remembering.” Natu- ral rewards affect dopamine activity in the same way, but psychoactive drugs can do it more powerfully. In doing so, these drugs can “hijack” a natural process in our brains.45

The personal and social problems associated with drug-taking behavior are examined in Chapter 2.

24 ■ Part One Drugs in Society/Drugs in Our Lives

P O r T r A i T From Oxy to Heroin: The Life and Death of Erik

Erik lived in a suburban Long Island, New York, community, and heroin killed him in 2008 at the age of 19. His mother, Linda D., never imagined what she was up against. “You worry,” she has said, “about them smoking pot. You worry about them driving recklessly. You worry about them not using their seat belt. You worry about that phone call in the middle of the night. You don’t worry about heroin. Because it didn’t exist in my mindset.”

In the last few years, the reality of heroin in the suburbs and small towns of America, previously considered to be immune from its deadly reach, has hit home with a sudden and un- expected vengeance. As a director of a local drug counseling center has expressed it, “They’re starting younger, they’re starting with more substances, they have better access, everything is cheaper, and they have more money.” You would call that a perfect storm.

Heroin arrests have doubled; rehabilitation-facility admissions

of those 21 and under for prescription pain reliever dependence have tripled or quadrupled in many cases.

In the case of Erik, it began after an emergency appendectomy with a prescription for Vicodin. Erik gradu- ally entered into a shadowy world of drug-taking behavior. Finding new supplies of Vicodin, then shifting to OxyContin, was easy. “It sounded grimy and sleazy,” a teenager would say in reference to her own depen- dence on prescription pain relievers, “but at the time it was just what I did. Everyone knows someone who can get them for you.”

At some point in early 2008, according to Linda, “The oxys dried up.” Erik turned from pills to heroin. “It started at a party,” she has said. “Someone said to him, ‘Oh, try this.’” By May, Linda and her hus- band realized Erik was using heroin.

In the weeks that followed, they tried to convince him to get help. The family’s insurance covered Erik’s first trip to a rehabilitation facility in upstate New York, but when Erik left after three days, the insurance company told the family that he had used up their “once in a lifetime” rehabilitation coverage. They tried to convince public hospitals to admit Erik, but he was denied. In the meantime, Erik’s parents were finding injection needles around the house and discarded rubber tubing. They desperately tried to cobble together funds to pay for rehabilita- tion, but they didn’t succeed in time. Erik died in July.

Sources: Lefrowitz, M. (2009, June 14). Heartbreak of addiction hits home. Newsday, pp. A4–A6. Archibold, R. C. (2009, May 31). In heartland death, traces of heroin’s spread. New York Times, pp. 1, 24.

Summary

Social messages about Drug use ● Unfortunately, we live in a social environment that

sends us mixed messages with respect to drug use. Cigarette smoking is still often portrayed in a posi- tive light in movies and other forms of entertainment media, despite persistent reminders of health hazards related to tobacco use. Beer commercials on televi- sion constitute popular forms of entertainment as well as effective marketing tools, despite the fact that alcohol abuse and alcoholism continue to present serious personal and societal problems. Prominent political figures admit to experiences with marijuana earlier in their lives, while marijuana remains of- ficially classified by the U.S. government as a drug with a high potential for abuse and no accepted medical use.

● Anti-drug campaigns in the media compete with pro–drug-use messages arising from the entertain- ment industry as well as Internet web sites.

Two ways of looking at Drugs and behavior ● Psychoactive drugs are those drugs that affect our feel-

ings, perceptions, and behavior. Depending on the intent of the individual, drug use can be considered either instrumental or recreational.

● Drug misuse refers to cases in which a prescription or over-the-counter drug is used inappropriately. Drug abuse refers to cases in which a licit or illicit drug is used in ways that produce some form of impairment.

Drugs in early Times ● Probably the earliest experiences with psychoactive

drugs came from tasting naturally growing plants. In- dividuals with knowledge about such plants were able to attain great power within their cultures.

● Ancient Egyptians and Babylonians in particular had extensive knowledge of both psychoactive and non- psychoactive drugs. Some of these drugs had genuine beneficial effects.

Chapter 1 Drugs and Behavior Today ■ 25

Drugs in the Nineteenth Century ● Medical advances in the 1800s succeeded in the iso-

lation of active ingredients within many psychoactive substances. For example, morphine was identified as the major active ingredient in opium.

● Psychoactive drugs were in widespread use, princi- pally in the form of patent medicines. Only by the end of the century were the risks of drug dependence beginning to be recognized.

Drugs and Behavior in the Twentieth Century ● Increased concern about the social effects of drug de-

pendence led to restrictive legislation regarding the use of morphine, heroin, cocaine, and marijuana.

● Social pressure from the temperance movement resulted in the national prohibition of alcohol con- sumption in the United States from 1920 to 1933.

● After 1945, important strides were made in the devel- opment of antibiotics and psychiatric drugs.

● By the 1940s and 1950s, illicit drugs such as heroin, cocaine, and marijuana were outside the mainstream of American life.

● In the 1960s and 1970s, the use of marijuana and hal- lucinogenic drugs spread across the nation, along with an increase in problems related to heroin.

● A decline in heroin abuse in the 1980s was matched by an increase in cocaine abuse and the emergence of crack as a cheap, smokable form of cocaine.

Present-Day Attitudes Toward Drugs ● It is now recognized that a wide range of psychoactive

drugs, licit or illicit, qualify as potential sources of misuse and abuse.

● Individuals born toward the end of the “baby boom” generation were the first group to have grown up during the explosion of drug experimentation in the 1960s and 1970s. Now, as the parents of teenagers at the beginning of the twenty-first century, they face the difficult challenge of dealing with the present-day drug-taking behavior of their children. Interestingly, there appears to be no relationship between prior mar- ijuana use among parents and marijuana use by their children.

Patterns of Drug Use in the United States ● In 2011, approximately one out of three high school

seniors used marijuana over the past year and one out of sixteen seniors used marijuana on a daily basis. Marijuana smoking represents the overwhelming pro- portion of illicit drug use in this population.

● The prevalence rate in 2011 for alcohol use in the past month among high school seniors was 40 percent and among college students was 64 percent. Roughly 10 percent of high school seniors and 7 percent of college students smoked at least one cigarette every day in 2011.

● In 2011, more than 21 million Americans aged twenty- six or older had used an illicit drug of some kind dur- ing the past twelve months. More than 15 million Americans used marijuana or hashish, and more than 8 million Americans engaged in the recreational use of a prescription pain reliever during this time period.

Making the Decision to Use Drugs ● Risk factors for drug-taking behavior in adolescence

include a tendency toward nonconformity within society and the influence of drug-using peers.

● Protective factors for drug-taking behavior include an intact home environment, a positive educational experience, and conventional peer relationships.

Present-Day Concerns ● Predictions regarding future drugs and drug-taking be-

haviors are largely founded on patterns from the past. New drugs will undoubtedly come on the scene; old drugs that are out of favor might regain popularity.

● A serious concern in recent years has been the emer- gence of a group of drugs referred to as club drugs. They include MDMA (Ecstasy), GHB, ketamine, Rohypnol, methamphetamine, and LSD.

● Relatively high prevalence rates for recreational use of prescription drugs and over-the-counter drugs among young people have raised serious concerns. Examples of abused drugs in these categories include prescrip- tion pain medications such as Percocet, Vicodin, and OxyContin; prescription stimulant medications such as Ritalin and Adderall; and dextromethorphan in popular over-the-counter cough-and-cold remedies.

Key Terms

chlorpromazine, p. 12 drug, p. 5 drug abuse, p. 7 drug dependence, p. 4 drug misuse, p. 7

Ebers Papyrus, p. 10 illicit drugs, p. 4 instrumental use, p. 6 licit drugs, p. 4 neuroscience, p. 13

patent medicine, p. 11 placebo effect, p. 10 protective factors, p. 19 psychoactive drugs, p. 4 recreational use, p. 7

risk factors, p. 19 shaman, p. 10 shamanism, p. 9

26 ■ Part One Drugs in Society/Drugs in Our Lives

endnotes

1. The Gallup Organization (2011, March 21). Americans’ worries about economy, budget top other issues. Wax, P. M. (2002). Just a click away: Recreational drug web sites on the Internet. Pediatrics, 109, 96.

2. Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2012, December 19). Decline in teen smoking continues in 2012. University of Michi- gan News Service, Ann Arbor, MI, Table 1. Centers for Disease Control and Prevention (2012, January 13). Vital signs: Binge drinking prevalence, frequency, and intensity among adults—United States, 2010. Morbidity and Mortality Weekly, 61, 14–19. Substance Abuse and Mental Health Services (2012, February 16). More than 7 million children live with a parent with alcohol prob- lems. Data Spotlight. Rockville, MD: Substance Abuse and Mental Health Services Administration. The path to smoking addiction starts at very young ages. Campaign for Tobacco-Free Kids, Washington DC. Accessed at www. tobaccofreekids.org/research/factsheets/pdf/0127.pdf.

3. Courtesy of the Drug Enforcement Administration, U.S. Department of Justice, Washington, DC, 2013. Klein- feld, N. R. (2012, January 12). Prescriptions of oxyco- done rose sharply in New York. New York Times, p. A22. National Institute on Drug Abuse (2011, October). Prescription drug abuse and addiction. NIDA Research Report Series. Rockville MD: National Institute on Drug Abuse. Warner, M; Chen L. H.; Makuc, D. M.; Ander- son, R. N.; Miniño (2011, December). Drug poisoning deaths in the United States, 1980-2008. NCHS Data Brief, No. 81. Atlanta: Centers for Disease Control and Prevention. Updated information from the Centers for Disease Control and Prevention, 2012.

4. Centers for Disease Control and Prevention (2012, January). Binge drinking: Nationwide problem, local solutions. Atlanta, GA: Centers for Disease Control and Prevention. Substance Abuse and Mental Health Ser- vices Administration (2009, December 29). Illicit drug use among older adults. The NSDUH Report, Figures 1 and 2. Substance Abuse and Mental Health Services Administration (2010, February 18). Substance use among black adults. The NSDUH Report, Figures 2 and 3.

5. Forman, R. F. (2003). Availability of opioids on the Internet. Journal of American Medical Association, 290, 889. Levy, C. J. (2005, October 9). Drink, don’t drink. New York Times, p. 14. Primack, B. A.; Dalton, M. A.; Carroll, M. V.; Agarwal, A. A.; and Fine, M. J. (2008). Content analysis of tobacco, alcohol, and other drugs in popular music. Archives of Pediatrics and Adolescent Medicine, 162, 169–175. Snyder, L. B., and Nadorff, P. G. (2010). Youth substance use and the media. In L. M. Scheier (Ed.), Handbook of drug use etiology: Theory, methods, and empirical findings. Washington, DC: American Psychological Association, pp. 475–491.

6. Leshner, A. I. (1998, October). Addiction is a brain disease—and it matters. National Institute of Justice Journal, 2–6. Wise, R. A. (2000). Addiction becomes a brain disease. Neuron, 26, 27–31.

7. Jacobs, M. R., and Fehr, K. O’B. (1987). Drugs and drug abuse: A reference text. Toronto: Addiction Research Foundation, pp. 3–5.

8. Goode, E. (2008). Drugs in American society (7th ed.). New York: McGraw-Hill College, pp. 13–19.

9. Caldwell, A. E. (1970). Origins of psychopharmacology: From CPZ to LSD. Springfield, IL: C. C. Thomas, p. 3. Muir, H. (2003, December 20; 2004, January 9). Party animals. New Scientist, pp. 56–59.

10. Bryan, C. P. (1930). Labate, B. C. (2011). Consumption of ayahuasca by children and pregnant women: Medi- cal controversies and religious perspectives. Journal of Psychoactive Drugs, 43 (1), 27–35. Metzner, R. (1998). Hallucinogenic drugs and plants in psychotherapy and shamanism. Journal of Psychoactive Drugs, 30, 333–341.

11. Grilly, D. M., and Salamone, J. D. (2012). Drugs, brain, and behavior (6th ed.). Boston: Pearson Education, p. 321.

12. Sneader, W. (1985). Drug discovery: The evolution of modern medicines. New York: Wiley, pp. 15–47.

13. Levinthal, C. F. (1988). Messengers of paradise: Opi- ates and the brain. New York: Anchor Press/Doubleday, pp. 3–25.

14. Bugliosi, V. (1991). Drugs in America: The case for vic- tory. New York: Knightsbridge Publishers, p. 215.

15. Freud, S. (1884). Über Coca (On Coca). Central-blatt für die gesammte Therapie. Translated by S. Pollak (1884). St. Louis Medical and Surgical Journal, 47.

16. Inciardi, J. A. (2002). The war on drugs III. Boston: Allyn and Bacon, p. 24.

17. Aaron, P., and Musto, D. (1981). Temperance and prohi- bition in America: A historical overview. In M. H. Moore and D. R. Gerstein (Eds.), Alcohol and public policy. Washington, DC: National Academy Press, pp. 127–181.

18. Helmer, J. (1975). Drugs and minority oppression. New York: Seabury Press. Schlosser, Eric (2003). Reefer mad- ness: Sex, drugs, and cheap labor in the American black market. Boston: Houghton Mifflin, p. 245. Smoking prevalence among U.S. adults, 1955–2007. U.S. Centers for Disease Control and Prevention, Atlanta, GA.

19. Cantor, N. F. (1969). Western civilization: Its genesis and destiny. Vol. 2. New York: Scott, Foresman.

20. Courtwright, D. (2001). Forces of habit: Drugs and the making of the modern world. Cambridge, MA: Harvard University Press. Egan, Timothy (1999, February 28). War on crack retreats, still taking prisoners. New York Times, pp. 1, 22–23.

21. Kandel, D. B.; Griesler, P. C.; Lee, G.; Davies, M.; and Schaffsan, C. (2001). Parental influences on adolescent marijuana use and the baby boom generation: Findings

Chapter 1 Drugs and Behavior today ■ 27

from the 1976–1996 National Household Survey on Drug Abuse. Rockville, MD: Substance Abuse and Mental Health Services Administration. Merlino, A. C.; O’Malley, P. M.; Schulenberg, J. E.; Bachman, J. G.; and Johnston, L. D. (2004). Substance use among adults 35 years of age: Prevalence, adulthood predictors, and impact of adolescent substance use. American Journal of Public Health, 94, 96–102. Wallace-Wells, B. (2012, December 3) The truce on drugs: What happens now that the war has failed? New York Times Magazine, pp. 30–35, 104–106.

22. Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2012a). Monitoring the Future: National survey results on drug use, 1975–2011. Vol. I: Secondary school students 2011. Ann Arbor, MI: Insti- tute for Social Research, The University of Michigan. Tables 2-2 and 2-4. Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2012b). Moni- toring the Future: National survey results on drug use, 1975–2011. Vol. II: College students and adults ages 19–50, 2011. Ann Arbor, MI: Institute for Social Research, The University of Michigan.

23. Johnston, O’Malley, Bachman, and Schulenberg, Moni- toring the Future, Vol. I, Table 2-2.

24. Johnston, O’Malley, Bachman, and Schulenberg, Moni- toring the Future, Vol. II, Tables 2-1, 2-2, and 2-3.

25. Johnston, O’Malley, Bachman, and Schulenberg, Moni- toring the Future, Vol. I, Tables 5-2 and 5-4.

26. Ibid, Tables 9-6 and 9-8. 27. Johnston, O’Malley, Bachman, and Schulenberg,

Monitoring the Future, Vol. II, Tables 2.3, 2.4, 9-3, and 9-4. 28. Johnston, O’Malley, Bachman, and Schulenberg, Moni-

toring the Future, Vol. I, Table 2-4. 29. Johnston, O’Malley, Bachman, and Schulenberg, Moni-

toring the Future, Vol. II, Table 2-4. 30. Johnston, O’Malley, Bachman, and Schulenberg, Moni-

toring the Future, Vol. I, Tables 2-3, 8-1, and 9-8. 31. Johnston, L. D. (1996, December 19). The rise in drug use

among American teens continues in 1996. News release from the University of Michigan, Ann Arbor, pp. 6–7.

32. Johnston, L. D.; O’Malley, P.M.; Bachman, J. G.; and Schulenberg, J. E. (2011, December 14). Marijuana use continues to rise among U.S. teens, while alcohol use hits historic lows. University of Michigan News Service, Ann Arbor, MI. Johnston, O’Malley, Bachman, and Schulenberg, Monitoring the Future, Vol. I, Table 8-6.

33. Substance Abuse and Mental Health Services Admin- istration. (2012). Results from the 2011 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services

Administration, Tables 1.22A, 1.22B, 1.27A, 1.27B, 1.52A, and 1.52B.

34. Johnston, L., and O’Malley, P. M. (1986). Why do the nation’s students use drugs and alcohol? Self-reported reasons from nine national surveys. The Journal of Drug Issues, 16, 29–66.

35. Goode, Drugs, pp. 73–75. 36. Wright, D., and Pemberton, M. (2004). Risk and pro-

tective factors for adolescent drug use: Findings from the 1999 National Household Survey on Drug Abuse. Rockville, MD: Substance Abuse and Mental Health Services—Administration, Chapter 3 and Appendix A.

37. Scheier, L. M.; Botvin, G. J.; and Baker, E. (1997). Risk and protective factors as predictors of adolescent alcohol involvement and transitions in alcohol use: A prospective analysis. Journal of Studies in Alcohol, 58, 652–667.

38. Wright and Pemberton, Risk and protective factors, Chapter 3 and Appendix A.

39. Smith, C.; Lizotte, A.J.; Thornberry, T. P.; and Krohn, M. D. (1995). Resilient youth: Identifying factors that prevent high-risk youth from engaging in delinquency and drug use. In J. Hagan (Ed.), Delinquency and disrepute in the life course. Greenwich, CT: JAI Press, pp. 217–247.

40. Inciardi, War on drugs. Archibald, R.C. (2009, May 31). In heartland death, traces of heroin’s spread. New York Times, pp. 1, 24.

41. Substance Abuse and Mental Health Services Admin- istration (2004, July). Club drugs, 2002 update. The DAWN Report. Rockville, MD.: Substance Abuse and Mental Health Services Administration, pp. 1–4.

42. Substance Abuse and Mental Health Services Adminis- tration (2008, June 19). Nonmedical use of pain relievers in substate regions: 2004 to 2006. The NSDUH Report, pp. 1–4. Substance Abuse and Mental Health Services Administration, Results from the 2011 National Survey on Drug Use and Health: Detailed tables, Table 1.56A.

43. Substance Abuse and Mental Health Services Adminis- tration, Results from the 2011 National Survey on Drug Use and Health: Detailed tables, Tables 7-23A and 7-23B.

44. Substance Abuse and Mental Health Services Admin- istration (2008). The abuse of prescription and over-the- counter drugs. Rockville, MD: Substance Abuse and Mental Health Services Administration. Substance Abuse and Mental Health Services Administration (2007, January 10). Misuse of over-the-counter cough and cold medications among persons aged 12 to 25. The NSDUH Report, pp. 1–4.

45. Friedman, R. A. (2010, Augusut 31). Lasting pleasures, robbed by drug abuse. New York Times, p. D6.

28

After you have completed this chapter, you should have an understanding of

▶ Dose-response curves as measures of drug toxicity

▶ The DAWN statistics as measures of drug-related medical emergencies

▶ The consequences of drug tolerance effects in drug abuse

▶ Physical dependence and psychological dependence

▶ Diagnosing drug-related problems by health professionals

▶ The impact of drug abuse on pregnancy and the risk of HIV infection

▶ The relationship between drug abuse and violent crime

▶ U.S. drug-enforcement policy and the regulation of drug-taking behavior

▶ Drug law enforcement and global politics

Drug-Taking Behavior: Personal and Social Issues

C h a p t e r

2

I’m a park ranger assigned to a small community park, basi-

cally three manicured baseball fields and about four acres of

woods, in the middle of a moderate-income-to-affluent subur-

ban town. About a hundred yards into the woods is a hangout

where the debris includes a home-made bong used to smoke

drugs and lots of needles. Heroin used to be the last thing on

the minds of public safety officers and unarmed park rang-

ers like myself just a few years ago. Now we find heroin even

in cars outside youth baseball games, less than twenty yards

away from kids and parents. Last night, a young man was

spotted wandering around the park. We knew that he had

been arrested with 77 pills about three weeks ago. But there he

was again, looking dazed and disoriented. Fresh needle marks

were seen on the inside of both his arms; his car smelled of

marijuana. He was clean and his car was clean, so the police

had to let him go. “We’ll see him again,” the police officer said.

Three hours later, he was spotted outside an all-night

fast-food place hustling OxyContin.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 29

Ask someone whether drugs present a major problem in the United States today, and you will get a loud, clear, affirmative answer.1 We all recognize that drug-taking behavior, specifically the abuse of either illicit or licit drugs, seriously undermines America’s family life, economy, public health, and public safety. But some- times it is difficult to appreciate how big of a problem it really is—in economic terms and in our personal lives:

■ Each year, we spend in the United States approxi- mately $25 billion on health care for either specialty services, behavioral consequences, or prevention of alcohol and illicit drug abuse. Health care costs associ- ated with tobacco use add another $96 billion annually.

■ Each year, we incur more than 106,000 premature deaths from alcohol and illicit drug abuse, represent- ing nearly $90 billion in productivity losses and more than 3 million years of “potential life lost.” These numbers are far greater when you consider the num- ber of premature deaths, productivity loss, and years of potential life lost as a result of tobacco use (see Chapter 10).2

Agreeing that we have a problem and seeing the enor- mous impact, however, are only the first steps. If we are to expend our energies, as well as public funds, on ways to reduce “the drug problem,” it is important to know or at least reach some degree of consensus about where the problems are and which problems are most deserving of our efforts. Here is where people disagree and controversy

exists. This chapter will concern itself with the specific aspects of drugs that are known to present significant problems for individuals and for society in general. It will then explore the response our society has made to these problems, in the form of governmental policy.

At the outset, it should be emphasized that the real culprits are not the drugs per se but rather certain forms of drug-taking behavior. If a drug, for example, were totally without any redeeming value (let us say it was extremely poisonous), most people would simply avoid it. It would be a “non-issue.” It would have no street value (other than perhaps to a terrorist), and no one would object to measures that restricted access to it. It would be a totally “bad” drug, but in terms of drug use, few people would care about it at all.

When we characterize heroin and cocaine as “bad drugs” (that is, drugs for which we need some govern- mental restriction of access), we are essentially saying that society has calculated the perceived risks of heroin or cocaine use against any potential social benefits. Heroin and other drugs such as opium and morphine are excellent painkillers and have been used medically in many countries of the world for a long time. In the case of opium, we are speaking of thousands of years of medical use. Cocaine is an excellent local anesthetic and has been used in a large number of medical pro- cedures in the United States. Nonetheless, society has decided that these positive applications in medicine are outweighed by the negative consequences for the gen- eral public, on both a personal and a social level.

The advantage of focusing on drug-taking behavior rather than simply on drugs themselves can be high- lighted by a bizarre but true story from the mid-1970s. At that time, a number of male patients were being treated for alcoholism in a Veterans Administration hos- pital in California. In one ward, a patient was observed moving his bed into the men’s room. Shortly afterward, several of his fellow patients, one by one, did the same.

What was behind this curious behavior? Evidently these men, deprived of alcohol after years of alcohol abuse, had discovered that drinking huge amounts of water (more than seven gallons a day) produced a “high” by altering the acid-to-base balance of their blood. They had found a highly dangerous but psychologically effec- tive way of getting drunk. The fact that they were also urinating approximately the same amount of water each day accounted for their decision to move into the men’s room.3 The point of the story is that in this case, water had become a psychoactive substance without techni- cally being a drug (recall the definition from Chapter 1). Once again, it is useful to focus on specific behaviors and their consequences, rather than on the substance itself.

by the numbers . . .

34 Percentage of approximately 2.5 million drug-related emergency department visits in the United States in 2011 that were due to the nonmedical use of prescription or non- prescription drugs alone.

720 Number of armed robberies of pharmacies in the United States in 2012, about twice as many as reported in 2006.

148 Percentage increase in the number of emer- gency department visits in the United States in 2011 due to the nonmedical use of a pre- scription or OTC medication, relative to 2004.

Sources: Substance Abuse and Mental Health Services Administration (2013). Drug Abuse Warning Network, 2011: National estimates of drug-related emergency department visits. Rockville, MD: Substance Abuse and Mental Health Services Administration. Armed robbery pharmacy incidents courtesy of the U.S. Department of Justice, 2013.

30 ■ Part One Drugs in Society/Drugs in Our Lives

In this chapter, our examination of personal and social concerns associated with drug-taking behavior will focus on three main questions:

■ What are the potential risks to one’s physical health and to the health of others?

■ What are the potential risks for physical and psycho- logical dependence?

■ What is the connection between drug-taking behavior and violence and crime?

Drug Toxicity

When we say that a drug is toxic, we are referring to the fact that it may be dangerous or poisonous or may in some way be interfering with a person’s normal function- ing. Technically, any substance, no matter how benign, has the potential for toxicity if the dose—the amount in which the substance is taken—is high enough. The question of a drug’s safety, or its relative safety when compared to other drugs, centers on the possibility that it may be toxic at relatively low doses. We certainly do not want people to harm themselves accidentally when taking the drug in the course of their daily lives. When there is a possibility that the short-term effects of a par- ticular drug will trigger a toxic reaction, then this drug is identified as having some level of acute toxicity.

To understand the concept of toxicity in more detail, we need to examine an S-shaped graph called the dose-response curve (Figure 2.1a). Let us assume we have the results of data collected from laboratory tests of a hypothetical sleep-inducing drug. Increases in the dose level of the drug will produce the desired sleep-inducing effect in an increasingly large percentage of a test popu- lation of mice. At 10 milligrams (mg), 50 percent of the population has fallen asleep; at 50 mg, 100 percent has done so. There is always some variability in individual reactions to any drug; some mice may be internally resis- tant to the drug’s effect, while others may be quite sus- ceptible. We cannot predict which specific animal might fall asleep with 10 mg of the drug, only that the probabil- ity of a given animal doing so is 50 percent.

We define the effective dose (ED) of a drug having a specific effect on a test population in terms of probabilities, from 0 percent to 100 percent. For example, the ED50 of a drug refers to the effective dose for 50 percent of the pop- ulation; ED99 refers to the effective dose for 99 percent of the population. In this case, the ED numbers refer to the drug’s effect of producing sleep on a specific proportion of the population being exposed to the drug. The same drug may be producing other effects (muscular relaxation,

for instance) at lower doses; these drug effects would have their own separate dose-response curves. Remember that we are looking at the properties of a specific drug effect here, not at the overall properties of the drug itself.

Now we can look at Figure 2.1b, where the effec- tive dose-response curve is represented next to another S-shaped dose-response curve, also gathered from labo- ratory testing, only in this case the “response” is death. It makes sense that the second curve should be shifted to the right because the lethal dose (LD) would gener- ally require a higher dosage of a drug than the dosage necessary to produce a nonlethal effect.

Emphasis should be placed on the word “gener- ally,” because the lethal dose-response curve may over- lap with the effective dose-response curve (as it does in this example). In the example shown, although a 100-mg dose needs to be taken to kill 50 percent of the test popu- lation, a dose of as little as 50 mg (or less) is lethal for at least a few of them. The LD50 of a drug refers to the lethal dose for 50 percent of the population; LD1 refers to a relatively lower dose that is lethal for only 1 percent of the population.

In order to arrive at an idea of a drug’s overall toxic- ity, we need to combine the effective and lethal doses of a drug in a ratio. The ratio of LD50/ED50 is called the therapeutic index. For example, if the LD50 for a drug is 450 mg, and the ED50 is 50 mg, then the therapeu- tic index is 9. In other words, you would have to take nine times the dose that would be effective for half of the population in order to incur a 50 percent chance of death in that population.

toxicity (tox-IS-ih-tee): The physical or psychological harm that a drug might present to the user.

dose: The quantity of drug that is taken into the body, typically measured in terms of milligrams (mg) or micrograms (μg).

acute toxicity: The physical or psychological harm a drug might present to the user immediately or soon after the drug is ingested into the body.

dose-response curve: An S-shaped graph showing the increasing probability of a certain drug effect as the dose level rises.

effective dose (ED): The minimal dose of a particular drug necessary to produce the intended drug effect in a given percentage of the population.

lethal dose (LD): The minimal dose of a particular drug capable of producing death in a given percent- age of the population.

therapeutic index: A measure of a drug’s relative safety for use, computed as the ratio of the lethal dose for 50 percent of the population to the effective dose for 50 percent of the population.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 31

It can be argued that a 50 percent probability of dying represents an unacceptably high risk even for a drug that has genuine benefits. To be more conservative in the direction of safety, the ratio of LD1/ED99 is often calculated. Here we are calculating the ratio between the dose that produces death in 1 percent of the popula- tion and the dose that would be effective in 99 percent. Naturally, this second ratio, called the margin of safety, should be as high as possible. As before, the higher the ratio, the greater the difference between effectiveness and lethality. In other words, the wider the margin of safety, the safer (less toxic) the drug in question. Clearly, the margin of safety for the hypothetical drug examined in Figure 2.1 would present serious toxicity issues.

The therapeutic index and the margin of safety are helpful measures when considering the toxicity of drugs that are manufactured by recognized pharmaceutical companies and regulated by the U.S. Food and Drug Administration (FDA), keeping in mind the possibility that a person might intentionally or unintentionally take a higher-than-recommended dose of the drug. But what about the toxicity estimates in the consumption of illicit drugs? The unfortunate reality of street drugs is that the buyer has no way of knowing what he or she has bought until the drug has been used, and then it is frequently too late. It is an extreme case of caveat emptor (“Let the buyer beware”).

Few if any illicit drug sellers make a pretense of being ethical businesspeople; their only objective is to make money and avoid prosecution by the law. Frequently,

the drugs they sell are diluted with either inert or highly dangerous ingredients. Adulterated heroin, for example, may contain a high proportion of milk sugar as inactive filler and a dash of quinine to simulate the bitter taste of real heroin, when the actual amount of heroin that is being sold is far less than the “standard” street dosage. At the other extreme, the content of heroin may be unex- pectedly high and may lead to a lethal overdose, or the adulterated product may contain animal tranquilizers, arsenic, strychnine, insecticides, or other highly toxic substances.4 Cocaine, LSD, marijuana, and all the other illicit drugs that are available to the drug abuser, as well as look-alike drugs that are unauthorized copies of popu- lar prescription medications, present hidden and unpre- dictable risks of toxicity. Even if drugs are procured from a friend or from someone you know, these risks remain. Neither of you is likely to know the exact ingredients. The potential for acute toxicity is always present.

Given the uncertainty that exists about the contents of many abused drugs, what measure or index can we use to evaluate the effects of acute toxicity on individu- als in our society? The natural tendency is to look first to the news headlines; think of all the well-known public figures who have died as a direct consequence of drug misuse or abuse (see Drugs . . . in Focus on page 32).

margin of safety: The ratio of a lethal dose for 1 percent of the population to the effective dose for 99 percent of the population.

F I g u r E 2 . 1

(a) An effective dose (ED)–response curve, and (b) an ED–response curve (left) alongside a lethal dose (LD)–response curve (right).

0

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50% fall asleep with 10 mg

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100% die with 200 mg

32 ■ Part One Drugs in Society/Drugs in Our Lives

Drugs . . . in Focus

Acute Toxicity in the News: Drug-Related Deaths The following famous people have died either as a direct consequence or as an indirect consequence of drug misuse or abuse.

Name Year

of Death Age Reasons Given for Death

Marilyn Monroe, actress 1962 36 Overdose of Nembutal (a sedative-hypnotic medication); circumstances unknown

Lenny Bruce, comedian 1966 40 Accidental overdose of morphine Judy Garland, singer and actress 1969 47 Accidental overdose of sleeping pills Janis Joplin, singer 1970 27 Accidental overdose of heroin and alcohol Jimi Hendrix, singer and guitarist 1970 27 Accidental overdose of sleeping pills Elvis Presley, singer and actor 1977 42 Cardiac arrhythmia suspected to be due to an interaction

of antihistamine, codeine, and Demerol (a painkiller), as well as Valium and several other tranquilizers

John Belushi, comedian and actor 1982 33 Accidental overdose of heroin combined with cocaine David A. Kennedy, son of U.S. senator Robert F. Kennedy

1984 28 Accidental interaction of cocaine, Demerol, and Mellaril (an antipsychotic medication)

Len Bias, college basketball player 1986 22 Cardiac-respiratory arrest from accidental overdose of cocaine

River Phoenix, actor 1993 23 Cardiac-respiratory arrest from accidental combination of heroin and cocaine

Jonathan Melvoin, keyboardist for the Smashing Pumpkins rock band

1996 34 Accidental overdose of heroin

Chris Farley, comedian and actor 1998 33 Accidental overdose of heroin and cocaine Bobby Hatfield, singer, the Righteous Brothers

2003 63 Heart failure following overdose of cocaine

Mitch Hedberg, comedian 2005 37 Heart failure due to “multiple drug toxicity,” including heroin and cocaine

Heath Ledger, actor 2008 28 Acute intoxication from combined use of six prescription medicines for pain, anxiety, insomnia, and nasal congestion

Michael Jackson, songwriter and entertainer

2009 50 Cardiac arrest due to an intramuscular administration of propofol (brand name: Diprivan), possibly interacting with a number of antianxiety medications

Greg Giraldo, comedian 2010 44 Accidental overdose of prescription medication and alcohol

Amy Winehouse, singer 2011 27 Accidental alcohol poisoning, resulting from a lethal blood- alcohol concentration of 0.42 percent

Whitney Houston, singer and actress

2012 48 Accidental drowning, with chronic cocaine use and heart disease as contributing factors.

Note: Celebrities whose drug-related deaths have been attributed to the toxicity of nicotine, tars, or carbon monoxide in tobacco products are not included in this listing.

Source: Various media reports.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 33

Such examples, however, can be misleading. Celebrities are not necessarily representative of the drug-using population in general, and the drugs preva- lent among celebrities, because of their expense, may not represent the drugs most frequently encountered by the rest of society. To have some idea of the toxic effects of psychoactive drugs in a broader context, we have to turn to the institutions that contend with drug toxicity on a daily basis: the emergency departments of hospitals around the country. As we will see, the drugs involved in hospital emergencies are not necessarily the ones that are associated with illicit drug use.

The DAwN Reports

The U.S. government currently gathers data concerning drug-related medical emergencies in major metropoli- tan hospitals through a program called the Drug Abuse Warning Network (DAWN). Two basic types of infor- mation are reported. The first concerns the number of times an individual visits an emergency department (ED, not to be confused with the ED used to indicate “effective dose”) for any reason that is connected to recent drug use. These drug-related ED visits involve a wide range of drug-related situations: suicide attempts, malicious poisoning, overmedication, and adverse reac- tions to medications, as well as the use of illicit drugs, the use of dietary supplements, and the nonmedical use of prescription or over-the-counter (OTC) drugs. The second type of information concerns the number of drug-related deaths, as determined by a coroner or medi- cal examiner.5

Approximately 2.5 million ED visits in the United States in 2011 (one-half of the total number of drug-related ED visits) were associated with either drug abuse or drug misuse, with an average of two drugs being reported in a given drug-related ED visit. About a third of the time, a drug-related ED visit involved more than one drug, and in some cases, there were five or more drugs mentioned at the time. The circumstances of drug-taking behavior involving multiple drugs is referred to as polydrug use.

Drug Abuse Warning Network (DAWN): A federal program in which metropolitan hospitals report the incidence of drug-related lethal and nonlethal emergencies.

drug-related ED visit: An occasion on which a person visits an emergency department (ED) for a purpose that is related to recent drug use.

polydrug use: Drug-taking behavior involving multiple drugs.

Quick Concept Check 2.1

Understanding Dose-Response Curves Check your understanding of dose-response curves and the toxicity of drugs by answering the questions below.

The following three sets of dose-response curves show the effective and lethal responses to three drugs, A, B, and C.

Answer: Drug B is the least toxic drug. Drug C is the most toxic drug.

Which of the three drugs would be considered the least toxic? Which would be considered the most toxic?

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34 ■ Part One Drugs in Society/Drugs in Our Lives

Figure 2.2 shows the distribution of ED visits associ- ated with either drug abuse or drug misuse with respect to seven circumstances. The percentage of these ED visits involving prescription or OTC medications alone (34 percent) was greater than the percentage involv- ing illicit drugs alone (27 percent), and the percentage involving medications in some combination (57 percent) was greater than the percentage involving illicit drugs in some combination (51 percent).6 The proportion

of drug-related ED visits involving alcohol use (see Figure 2.2) requires some explanation. Statistics about ED visits related to the use of alcohol alone are limited in the DAWN reporting system to such use by indi- viduals younger than twenty-one years of age. In other words, such medical emergencies are resulting, by def- inition, from underage drinking. DAWN statistics are not collected for ED visits involving alcohol use alone by individuals who are twenty-one years old or older.

There is a very good reason for this exclusion. If all emergencies related to alcohol use alone were reported, the numbers would far exceed those related to any other drug. Considering the number of alcohol-related auto- mobile accidents and alcohol-related personal injuries that end up in emergency departments each year (see Chapter 8), the examination of ED visits related to other circumstances would be totally obscured if all alcohol- related ED visits were included.

An important message in the DAWN statistics is the considerable toxicity that is reflected in the alcohol-in- combination category of ED visits. In these circumstances, the ingestion of alcohol has occurred in conjunction with the ingestion of another drug, regardless of one’s age. About one-fourth (24 percent) of drug-related ED visits in 2011 involved some use of alcohol in combination with either an illicit drug, with a prescription or nonpre-

scription medication, or with an illicit drug and a medication.7

Emergencies Related to Illicit Drugs What types of illicit drugs are most likely to result in an ED visit? Among drug-abuse and drug- misuse ED visits reported in 2011, the largest number involved cocaine (40 percent), followed by marijuana (36 percent), heroin (21 percent), and methamphetamine (13 percent). Notice that the percentages for these drugs add up to more than 100 percent, because of the involvement of two or more drugs at a time. In general, patients admitted for an illicit-drug-related ED visit in 2011 were about twice as likely to be male as female.8

Drug-Related Deaths Current DAWN statistics on the number of drug- related deaths in the United States are not reported on a nationwide basis but instead in terms of selected metro- politan areas. This presents certain challenges in draw- ing conclusions about lethality of drug-taking behavior

Medications only

Illicit drugs with alcohol and medications

Illicit drugs only

Alcohol with medications

Illicit drugs with

medications

Illicit drugs with alcohol

11%

10%

10%

3%

34%

27%

5%

Alcohol only (age <21)

Emergency medical service (EMS) crews frequently have to deal with drug-related cases.

F I g u r E 2 . 2

Distribution of drug-related emergency department visits in 2011 by type of drug involvement. Here, and in the accompanying text discussion, ED stands for “emergency department.”

Source: Substance Abuse and Mental Health Services Administration (2013). Drug Abuse Warning Network, 2011: National estimates of drug-related emergency department visits, 2004–2011. Rockville, MD: Substance Abuse and Mental Health Services Administration.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 35

in a particular region of the country. For example, a similar number of drug-related deaths in 2010 in met- ropolitan Washington, DC, and metropolitan Denver, Colorado (353 versus 356), with very different popula- tions (5.5 million versus 2.5 million), is indicative of a substantially greater drug problem in Denver as com- pared to Washington, DC. In mathematical terms, we are using two different denominators in arriving at the prevalence rate.

In addition, a particular metropolitan area in the DAWN survey may have a somewhat different “profile” in terms of five drugs most frequently reported in drug- related death cases. Despite these differences, however, a number of generalizations can still be made, based on the 2010 statistics.

■ It is far more common for drug-related deaths to be a result of multiple-drug (polydrug) use than a result of single-drug (monodrug) use.

■ In nearly all metropolitan areas surveyed in the DAWN report, an opioid drug (heroin, morphine, methadone, or opioid pain medication) is the most frequently reported drug involved in a drug-related death incident.

■ Cocaine is typically reported in 2010 among the top three drugs in these circumstances, while it had been the most frequently reported in earlier years.

■ Alcohol (that is, alcohol in combination with some other drug) is commonly in second or third place and is almost always in the “top five.”

■ Medications used to treat anxiety or depression are almost always among the top five most frequently reported drugs in drug-related death cases. How- ever, the presence of these categories of licit drugs in the “top five” listing should be interpreted carefully. The amounts ingested in these circum- stances far exceed the recommended dosage levels and have been, like alcohol, combined with one or more other drugs.

■ Marijuana is far less prominent in drug-related deaths, and when there are reports of its involvement, it is al- most exclusively in the context of multiple-drug rather than single-drug use.

■ Methamphetamine use as a cause of a drug-related death is largely underestimated in the DAWN sta- tistics, because of reliance on reports from large metropolitan areas rather than from smaller, rural areas in the United St ates, where methamphet- amine has been a significant public health concern (see Chapter 4).9

Judging Drug Toxicity from Drug-Related Deaths The finding that the use of heroin or cocaine alone is frequently involved in drug-related deaths is particularly striking when you consider that heroin and cocaine users constitute a relatively small proportion of the total number of illicit drug users, and certainly of the gen- eral population. The fact that there are more instances of drug-related deaths resulting from heroin use than instances of cocaine use underestimates the potential lethality of heroin, since there are far fewer heroin users than cocaine users in the United States. In contrast, the rare association of marijuana with a drug-related death actually overestimates its potential lethality, given its widespread use within a much larger group of people.

In short, a judgment about the relative toxicity of illicit drugs requires an understanding of how frequently a particular drug is used in the general population. All other facts being equal, if one illicit drug produces twice as many deaths as a second drug, but the number of users of the first drug is twice that of the second, then the toxicity levels of the two drugs should be considered equivalent.

Demographics and Trends By examining DAWN statistics over the last thirty years or so, we can arrive at some idea of the changes that have taken place in the frequency of specific drug- related medical emergencies. For example, a dramatic increase in the number of cocaine-related emergencies occurred in the 1980s as a result of the rise of cocaine abuse and crack cocaine abuse. A decade later, an upturn in heroin-related emergencies took place during the 1990s, as the purity of available heroin increased and the availability of heroin use without a needle injection caused heroin-related emergency rates to rise.

In the mid-1990s, significant concerns emerged about the increase in ED visits arising from the use of illicit club drugs such as Ecstasy, GHB, ketamine, LSD, and methamphetamine. More recently, the class of drugs that have raised the greatest concern among health care professionals include opioid prescription medica- tions, also known as narcotic analgesics (see Chapter 5). In 2009, more than 15,000 people in the United States died from these medications, four times more than in 1999. The principal medications of this type are metha- done, oxycodone (brand name: Percocet), controlled- release oxycodone (brand name: OxyContin), and hydrocodone (brand name: Vicodin).10

36 ■ Part One Drugs in Society/Drugs in Our Lives

From Acute Toxicity to Chronic Toxicity

Through the DAWN surveys, we can appreciate the extent of acute toxicity involved in the ingestion of a particular drug, but we are unable to get an illuminating picture of the negative consequences of using a particu- lar drug over a long period of time. Examples of chronic toxicity can be found in a wide range of psychoactive drugs, either legally or illegally obtained. Ironically, it is the chronic use of alcohol and tobacco, both of

which are legally available in our society, that causes by far the greatest adverse health effects. As we will see in Chapters 9 and 10, the number of people who die each year as a result of drinking alcohol or smoking tobacco far outstrips the number of fatalities from the abuse of illicit drugs (Figure 2.3).

A number of important issues with respect to drug-taking behavior will be examined in the chapters ahead. What exactly are the problems associated with chronic drug use? What is the most productive way of looking at drug dependence in general? How has our society responded to the problems of drug-taking behavior over the years? How successful have we been in dealing with these problems? What new strategies are there to handle drug-related problems in a more effective way?

F I g u r E 2 . 3

U.S. deaths per year from tobacco, alcohol, and illicit drug use.

Sources: Centers for Disease Control and Prevention (2008, November 14). Cigarette smoking- attributable morbidity, years of potential life lost, and productivity losses—United States, 2000–2004. Morbidity and Mortality Weekly Report, 57, 1226–1228. Harwood, H. (2011, October 23). Recent findings on the economic impacts of substance abuse. Presented at the American Psychological Association 2011 Science Leadership Conference, Psychologi- cal Science and Substance Abuse, Washington DC, Slide 12. Mokdad, A.H.; Marks, J.S.; Stroup, D. F.; and Gerberding, J.L. (2004). Actual causes of death in the United States, 2000. Journal of the American Medical Association, 291, 1238–1245.

R.I.P.

Illicit Drugs

R.I.P.

Alcohol

R.I.P.

Tobacco

443,000

83,000

23,500

More than four times as many Americans die from tobacco-related illnesses such as cardiovascular and respiratory diseases and cancer as die from alcohol-related and illicit drug-related problems combined. Numbers of tobacco-related deaths include tobacco users or nonusers exposed to tobacco smoke.

chronic toxicity: The physical or psychological harm a drug might cause over a long period of use.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 37

Behavioral Tolerance and Drug Overdose

Legend has it that in the first century b.c., King Mithridates VI of Pontus, a region of modern-day Turkey near the Black Sea, grew despondent following a series of defeats by the Romans and decided to commit suicide by poison. The problem was that no amount of poison was sufficient, and the grim task had to be completed by the sword. It turned out that Mithridates, having lived in fear of being poisoned by his rivals, had taken gradually increasing amounts of poi- son over the course of his life to build up a defense against this possibility. By the time he wanted to end his life by his own hand, he could tolerate such large doses that poisoning no longer presented any threat to his life. This royal case is the first recorded example of drug tolerance. In fact, the phenomenon originally was called mithridatism, and sev- eral celebrated “poisoners” of history, including the notori- ous Lucretia Borgia in the early sixteenth century, were later to use the same strategy.11

The concept of tolerance refers to the capacity of a drug dose to have a gradually diminished effect on the user as the drug is taken repeatedly. Another way of viewing tol- erance is to say that over repeated administrations, a drug dose needs to be increased to maintain an equivalent effect.

A common illustration of drug tolerance is the effect of caffeine in coffee. When you are first intro- duced to caffeine, the stimulant effect is usually quite pronounced; you might feel noticeably “wired” after a 5-ounce cup of coffee containing approximately 100 mg of caffeine (see Chapter 11). But after several days or perhaps a few weeks of coffee drinking the effect is greatly diminished; you may need to be on the second or third cup by that time, consuming 200 to 300 mg of caffeine, to duplicate the earlier reaction. Some indi- viduals who drink coffee regularly have developed such high levels of tolerance to caffeine that they are able to sleep comfortably even after several cups of coffee, while individuals who drink coffee less often may find themselves awake through the night after a single cup.

The danger that the tolerance effect presents is the possibility of death by drug overdose, which is frequently

the cause of accidental drug-related deaths listed in the DAWN reports. Individuals involved in drug abuse are often taking drug doses that are precariously close to the LD-response curve amounts, as described earlier. These dosage levels may be sustainable by a drug abuser who has grown tolerant to the drug over repeated administra- tions but quite lethal to an individual being introduced to the drug for the first time.

In understanding the possibility of drug overdose, it is useful to look at the interaction between the actual amount of the drug taken and other factors involved in the drug-taking behavior. Although, as already noted, the number of previous times the drug has been used is crucial, another important factor is the setting within which the drug-taking behavior occurs. There is strong evidence that tolerance effects are maximized when the drug-taking behavior occurs consistently in the same sur- roundings or under the same circumstances. We speak of this form of tolerance as behavioral tolerance.12

To have a clear idea of behavioral tolerance, we first have to understand the basic facts of Pavlovian con- ditioning, upon which behavioral tolerance is based.

tolerance: The capacity of a drug to produce a gradually diminished physical or psychological effect upon repeated administrations of the drug at the same dose level.

behavioral tolerance: The process of drug tolerance that is linked to drug-taking behavior occurring con- sistently in the same surroundings or under the same circumstances. Also known as conditioned tolerance.

A heroin abuser suffering from a possibly lethal heroin over- dose immediately after injection.

38 ■ Part One Drugs in Society/Drugs in Our Lives

Suppose you consistently heard a bell ring every time you had a headache. Previously, bells had never had any negative effect on you. The association between the ringing bell and the pain of the headache, however, would become strong enough that the mere ringing of a bell would now give you a headache—perhaps less painful than the ones you had originally, but a head- ache nonetheless; this effect is Pavlovian conditioning at work.

A pioneering study by the psychologist Shepard Siegel showed a similar phenomenon occurring with drug-taking behavior. In his experiment, one group of rats was injected with doses of morphine in a particular room over a series of days and later tested for tolerance to that dose in the same room. Predictably, they dis- played a lessened analgesic effect as a sign of morphine tolerance. A second group was tested in a room other than the one in which the injections had been given. No tolerance developed at all. They reacted as if they had never been given morphine before, even though they had received the same number of repeated injec- tions as the first group.

In a more extreme experiment, Siegel tested two groups of rats that were administered a series of heroin injections with increasingly higher dosages. Eventually both groups were surviving a dosage level that would have been lethal to rats experiencing the drug for the first time. The difference in the groups was related to the environment in which these injections were given. One group received these injections in the colony room where they lived. When the second group were receiv- ing their injections, they were in a room that looked quite different and were hearing 60-decibel “white noise.” Siegel then administered a single LD100 dose of heroin, normally a level that should have killed them all. Instead, rats administered this extremely high dos- age in the same room in which they had received the earlier heroin injection series showed only a 32 percent mortality rate. When the room was different, however, the mortality rate doubled (64 percent). In both groups, more rats survived than if they had never received her- oin in the first place, but the survival rate was influenced by the environment in which the heroin was originally administered.

Siegel explained the results of his studies by assuming that environmental cues in the room where the initial injections were given elicited some form of effect opposite to the effect of the drug. In the case of heroin, these compensatory effects would partially counteract the analgesic effect of the drug and protect the animal against dying from potentially high dosage levels.

The phenomenon of behavioral tolerance, also referred to as conditioned tolerance because it is based on the principles of Pavlovian conditioning, explains why a heroin abuser may easily suffer the adverse con- sequences of an overdose when the drug is taken in a different environment from the one more frequently encountered or in a manner different from his or her ordinary routine.13 An individual’s tolerated dose of heroin can vary widely; amounts in the range of 200 to 500 mg may be lethal for a first-time heroin abuser, while amounts as high as 1,800 mg may not even be sufficient to make a long-term heroin abuser sick.14 You can imagine how dangerous it would be if the condi- tioned compensatory responses a heroin abuser had built up over time were suddenly absent.

Quick Concept Check 2.2

Understanding Behavioral Tolerance through Conditioning Check your understanding of behavioral tolerance as proposed by Shepard Siegel by answering the following questions.

1. Suppose you have a rat that has been placed in an en- vironment where it had been repeatedly injected with morphine. You now inject that rat with a saline solution (a substance that has no physiological effect). Assuming that morphine will make a person less sensitive to pain, how will this animal react to the saline injection? Will the rat be less sensitive to pain, will it be more sensitive to pain, or will there be no effect? Explain your answer.

2. If King Mithridates VI had changed palaces from time to time during his reign, what would have been the effect on his eventual level of drug tolerance to poison when he chose to attempt suicide?

Answers: 1. The rat will now be more sensitive to pain. The exposure to an environment associated with mor- phine injections will have induced a conditioned com- pensatory effect: a heightened sensitivity to pain. The saline injection produces no physiological effect of its own; however, because it is given in that same environ- ment where the morphine was administered, the condi- tioned effect will remain, and the rat’s reaction will be hyperalgesia. (The experiment has been performed, by the way, and this predicted outcome does occur.)

2. The king would probably have died. He would not have been able to develop a sufficient level of drug toler- ance to avoid succeeding in his suicide attempt.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 39

Behavioral tolerance also helps to explain why a formerly drug-dependent individual is strongly advised to avoid the surroundings associated with his or her past drug-taking behavior. If these surroundings pro- voked a physiological effect opposite to the effect of the drug through their association with prior drug- taking behavior, then a return to this environment might create internal changes and feelings of craving that only drugs could reverse. In effect, environmen- tally induced withdrawal symptoms would increase the chances of a relapse. The fact that conditioning effects have been demonstrated with respect not only to heroin but to alcohol, cocaine, nicotine, and other dependence-producing drugs as well makes it impera- tive that the phenomenon of behavioral tolerance be considered during the course of drug abuse treatment and rehabilitation.15

Another perspective on drug tolerance, based on physiological changes that occur as result of repeated drug administrations, will be discussed in Chapter 3.

Physical and Psychological Dependence

When we refer to the idea of dependence in drug abuse, we are dealing with a person who has a strong compulsion to continue taking a particular drug. Two possible models or explanations for why drug depen- dence occurs can be considered. The first is referred to as physical dependence, and the second is referred to as psychological dependence. The two models are not mutually exclusive; the abuse of some drugs can be a result of both physical and psychological dependence, and the abuse of others can be a result of psychological dependence alone.

Physical Dependence The concept of physical dependence originates from observations of heroin abusers, as well as of those who abuse other opioid drugs, who developed strong

physical symptoms following withdrawal: a runny nose, chills and fever, inability to sleep, and hypersensitivity to pain. For barbiturate abusers in a comparable situ- ation, symptoms include anxiety, inability to sleep, and sometimes lethal convulsions.16 For chronic alco- holic abusers, abstention can produce tremors, nau- sea, weakness, and tachycardia (a rapid heart rate). If severe, symptoms may include delirium, seizures, and hallucinations.17

Although the actual symptoms vary with the drug being withdrawn, the fact that we observe physical symptoms at all suggests strongly that some kind of physical need, perhaps as far down as the cellular level, develops over the course of drug abuse. It is as though the drug, previously a foreign substance, has become a normal part of the nervous system, and its removal and absence become abnormal.

From this point of view, it is predictable that the withdrawal symptoms would involve symptoms that are opposite to effects the drug originally had on the body. For example, heroin can be extremely consti- pating, but eventually the body compensates for hero- in’s intestinal effects. Abrupt abstinence from heroin leaves the processes that have been counteracting the constipation with nothing to counteract, so the result of withdrawal is diarrhea. You may have noticed a strong resemblance between the action/counterac- tion phenomena of withdrawal and the processes Siegel has hypothesized as the basis for behavioral tolerance.

Psychological Dependence The most import ant implication of the model of physical dependence, as distinct from psychological dependence, is that individuals involved in drug abuse continue their drug-taking behavior at least in part to avoid the feared consequences of withdrawal. This idea can form the basis for a general model of drug depen- dence only if physical withdrawal symptoms appear con- sistently for every drug considered as a drug of abuse. It turns out, however, that a number of abused drugs (cocaine, hallucinogens, and marijuana, for example) do not produce significant physical withdrawal symp- toms, and the effects of heroin withdrawal are more variable than we would expect if physical dependence alone were at work.

It is possible that drug abusers continue to take the drug not because they want to avoid the symptoms of withdrawal but because they crave the pleasurable effects of the drug itself. They may even feel that they

physical dependence: A model of drug depen- dence based on the idea that the drug abuser continues the drug-taking behavior to avoid the consequences of physical withdrawal symptoms.

40 ■ Part One Drugs in Society/Drugs in Our Lives

need the drug to function at all. This is the way one heroin abuser has expressed it:

I’m just trying to get high as much as pos- sible. . . . If I could get more money, I would spend it all on drugs. All I want is to get loaded. I just really like shooting dope. I don’t have any use for sex; I’d rather shoot dope. I like to shoot dope better than anything else in the world.18

A majority of heroin abusers (between 56 percent and 77 percent in one major study) who complete the withdrawal process after abstaining from the drug experience relapse into their former pattern of abuse.19 If physical dependence were the whole story, these phe- nomena would not exist. The withdrawal symp- toms would have been gone by that time, and any physical need that might have been evident before would no longer be present.

When we speak of psychological depen- dence, we are offering an explanation of drug abuse based not on the attempt of abusers to avoid unpleasant withdrawal symptoms but on their continued desire to obtain pleasurable effects from the drug. Unfortunately, we are faced here with a major conceptual problem: The explanation by itself is circular and tells us basically nothing. If I were to say, for example, that I was taking cocaine because I was psychologically dependent on it, then I could just as easily say that I was psychologically dependent on cocaine because I was abusing it. Without some independent justification, the only explanation for the concept of psychological dependence would be the behavior that the concept was supposed to explain!

Fortunately, there is independent evidence for the concept of psychological dependence, founded chiefly upon studies showing that animals are as capable of self-administering drugs of abuse as humans are. Using techniques developed in the late 1950s, research- ers have been able to insert a catheter into the vein of a freely moving laboratory animal and arrange the

equipment so that the animal can self-administer a drug intravenously whenever it presses a lever (Figure 2.4). It had been well known that animals would engage in specific behaviors to secure rewards such as food, water, or even electrical stimulation of certain regions of the brain. These objectives were defined as positive rein- forcers because animals would learn to work to secure them. The question at the time was whether animals would self-administer drugs in a similar way. Could drugs be positive reinforcers as well?

The experiments showed clearly that animals would self-administer drugs such as cocaine and other stimulants, despite the fact that these drugs would not ordinarily produce physical symptoms during with- drawal. In one study, rats pressed the lever as many as 6,400 times for one administration of cocaine; others were nearly as eager for administrations of amphet- amines.20 Interestingly, a number of other drugs were aversive, judging from the reluctance of animals to work for them. Hallucinogens such as LSD, antipsychotic

psychological dependence: A model of drug dependence based on the idea that the drug abuser is motivated by a craving for the pleasurable effects of the drug.

catheter (CATH-eh-ter): A device to deliver intrave- nous injections of a drug in a free-moving human or animal.

F I g u r E 2 . 4

A simplified depiction of how drugs are self-administered in rats. The rat’s pressure on a lever causes the pump to inject a drug through a catheter implanted into its vein.

Pump

Programming equipment

Catheter

Lever

Drug

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 41

drugs, and antidepressant drugs were examples of drugs that animals clearly did not like.21

By connecting the concept of psychological depen- dence to general principles of reinforcement, it is possible for us to appreciate the powerful effects of abused drugs. When an animal is presented with a choice of pressing a lever for food or pressing a lever for cocaine, cocaine wins hands down—even to the point of the animal starv- ing to death.22 When the effects of heroin are compared with those of cocaine, the differences are dramatic:

Those rats that self-administer heroin developed a stable pattern of use, maintained their pretest weight, continued good grooming behavior, and tended to be in good health. Their mortality rate was 36 percent after thirty days. Those self-administering cocaine . . . exhibited an extremely erratic pattern of use, with “binges” of heavy use alternating with brief periods of abstinence. They lost 47 percent of their body weight, ceased grooming behavior, and main- tained extremely poor physical health. After thirty days, 90 percent were dead.23

In the final analysis, from the standpoint of treat- ing individuals who abuse drugs, it might not matter whether there is physical dependence or psychological dependence going on. According to many experts in the field, the distinction between physical and psychologi- cal dependence has outgrown its usefulness in explain- ing the motivation behind drug abuse. Whether the discontinuation of an abused drug does induce major physical withdrawal symptoms (as in the case of heroin, alcohol, and barbiturates) or does not (as in the case of cocaine, amphetamines, and nicotine), the patterns of compulsive drug-taking behavior are remarkably simi- lar. If the pattern of behavior is the same, then there can be common strategies for treatment. Chapter 3 will examine the current understanding that most, if not all, drugs of abuse are linked together by virtue of common neurochemical processes in the brain.

Diagnosing Drug-Related Problems: The Health Professional’s Perspective

Health professionals in the United States use the Diagnostic and Statistical Manual of Mental Disorders (referred to as the “DSM”), issued under the auspices of the American Psychiatric Association, as the official

standard for defining and diagnosing a wide range of psychological problems. Since the 1980s, the hallmark feature has been that the diagnosis of a psychologi- cal disorder is determined on the basis of a number of behavioral criteria. In the case of problems associated with drug-taking behavior, one criterion might be that a person has been observed to have failed “to fulfill major role obligations at work, school, or home within a 12-month period.” A specific example would be the “neglect of children or one’s household.”

In addition, the phrase “substance use” has been used throughout, instead of “drug use.” The rationale for this decision is that confusion often exists in the pub- lic mind about what is defined as a drug (see Chapter 1) and what is not—particularly in the instance of alcohol or tobacco use. From 2000 to 2013, the fourth edition (text revision) of the DSM (referred to as DSM-IV-TR) defined two psychological disorders associated with drug-taking behavior: substance abuse and the more severe condition substance dependence (see Table 2.1). For example, one of the possible criteria for substance dependence is the observation that the person would try to stop a recurrent pattern of drug-taking behavior and repeatedly relapse into further drug use. Diagnoses of substance abuse and substance dependence were clas- sified under the general heading of substance-related disorders.

A new revision of the DSM (called DSM-5) was issued in 2013, with two major changes involving drug- taking behavior. First, the four possible criteria previously listed for the diagnosis of substance abuse and the seven possible criteria for the diagnosis of substance depen- dence have been essentially combined into one set of eleven criteria for a newly established diagnosis called substance use disorder. A minimum of two criteria

substance abuse: A diagnostic term used in the DSM-IV-TR for clinical psychologists, psychiatrists, and other health professionals to identify an individual who continues to take a psychoactive drug despite the fact that the drug-taking behavior creates specific problems for that individual.

substance dependence: A diagnostic term used in the DSM-IV-TR for clinical psychologists, psychiatrists, and other health professionals to identify an individual with significant signs of a dependent relationship with a psychoactive drug.

substance use disorder: A diagnostic term used in the DSM-5 for clinical psychologists, psychiatrists, and other health professionals to identify an individual with significant problems that are associated with some form of drug-taking behavior.

42 ■ Part One Drugs in Society/Drugs in Our Lives

CrITErIA For SubSTANCE DEpENDENCE

Three or more of the following conditions must have occurred within a 12-month period, lasted for more than a month or occurred repeatedly over a longer period of time:

1. Tolerance: Either the substance has been taken in increasingly large doses to produce the desired effect or a diminished effect has been experienced over time from the same amount of the substance.

2. Withdrawal: Psychological or physiological symptoms arise when use is stopped or use has continued in order to relieve or avoid these symptoms.

3. unintentional use in excessive amounts: The substance is often taken in larger amounts or over a longer period of time than has been intended by the user.

4. persistent intentions or efforts to cut down on substance use: There are frequent attempts to quit or reduce substance use and repeated failures (relapses) in doing so.

5. preoccupation: A great deal of time is spent in behaviors that are necessary to obtain the sub- stance, use the substance, or recover from its adverse effects.

6. reduction in fulfilling important personal responsibil- ities: Social, occupational, or recreational obligations are not fully met or abandoned in order to engage in substance use. Examples include quitting a job or neglecting the care of a child.

7. Continuing substance use even though there are major substance-related social or health problems: Examples include continuance of cocaine use despite recognition of a cocaine- induced depression or continuance of drinking despite recognition that an ulcer condition would be made worse.

CrITErIA For SubSTANCE AbuSE

Individuals meeting the criteria for substance abuse must never have met the criteria for substance dependence for this class of substance.

One or more of the following conditions must have occurred within a 12-month period:

1. recurring failure to meet major role obligations at work, school, or home due to substance use: Examples include repeated absenteeism at work, school suspensions or expulsions, or neglect of members of one’s household.

2. recurrence of substance use in physically hazardous situations or circumstances: Examples include driving while intoxicated or operating a machine while impaired by substance use.

3. recurrent legal difficulties related to substance use: Examples include arrests for disorderly conduct or other disruptive substance-related behaviors.

4. Continuing substance use even though the individual is aware of persistent social, occupational, psycho- logical or physical problems that would result or be made more difficult by the use of the substance: Examples include physical fights or spousal arguments related to substance use.

has been established for an individual to be identified as having a substance use disorder. Second, the DSM-5 has set a severity-of-symptoms scale for this condition. The presence of two or three criteria is considered to reflect a

mild level of substance use disorder, four or five criteria for a moderate level, and six or more for a severe level.

In the circumstance in which only one particular drug is involved, a substance use disorder is identified in

TAbLE 2.1

Summarizing the criteria for substance dependence and substance abuse, according to the DSM-IV-TR (prior to 2013) and substance use disorder, according to DSM-5 (effective 2013)

DSM-5 criteria for substance use disorder Criteria for substance use disorder in DSM-5 are nearly identical to the criteria for substance dependence and substance abuse in DSM-IV-TR combined into a single list, with two exceptions. The DSM-IV-TR criterion, recur- rent legal difficulties, for substance abuse has been deleted and a new criterion, craving or a strong desire or urge to use the substance, has been inserted as a replacement.

Two or more of these criteria must have occurred within a 12-month period of time for a diagnosis of sub- stance use disorder.

Note: Substances include alcohol (see Chapter 9), amphetamines, caffeine, cannabis, cocaine, hallucinogens, inhalants, opi- oids, phencyclidine, seduative-hypnotics, and anxity-reducing medications in DSM-IV-TR and in addition, tobacco in DSM-5.

Sources: American Psychiatric Association (2013). Highlights of changes from DSM-IV-TR to DSM-5. Washington, DC: American Psychiatric Association. American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders, text revi- sion (4th ed.). Washington DC: American Psychiatric Association.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 43

the context of that drug. As examples, the DSM-5 allows for the possibility of a diagnosis of stimulant use disor- der (see Chapter 4), opioid use disorder (see Chapter 5), hallucinogen use disorder (see Chapter 6), cannabis use disorder (see Chapter 7), or alcohol use disorder (see Chapter 9). While it may take some time for health professionals to adapt to the new DSM-5 guidelines, the change to a single diagnosis has been considered an improvement over guidelines in the previous editions of the DSM, in that it is simpler to use in the clinical treat- ment of substance-related problems.24

Special Circumstances in Drug Abuse

The discussion so far has dealt with drug-abuse problems, specifically the problems of acute and chronic toxicity, that affect only the drug user. Unfortunately, other peo- ple are frequently involved as well. Consider two special circumstances related to drug abuse that require discus- sions of their own: the problems of drug abuse in preg- nancy and drug use in association with HIV infection.

Drug Abuse in Pregnancy Prior to the 1960s, doctors and scientists regarded the placenta joining the bloodstream of a pregnant woman with that of the developing fetus as a natural barrier pro- tecting the fetus from toxic substances in the mother. We now know that the idea of a “placental barrier” is clearly wrong. During gestation, nearly all drugs cross the placenta and affect the unborn child.

It is clear that women who do engage in the con- sumption of licit or illicit drugs during pregnancy are at increased risk for obstetrical complications and for premature labor and delivery. They are also more likely to suffer loss of the fetus through spontaneous abor- tions (miscarriages) and stillbirths than are women who abstain from drugs. The greater the extent of drug-taking behavior, the more likely that there will be adverse consequences.

The timing of drug use during a pregnancy has a great deal to do with the specific risks to the fetus. Drug use during the early weeks of pregnancy, from the fourth to the eighth week following conception, is more likely to increase the risks of spontaneous abortions and physi- cal malformations in the newborn than drug use later in the pregnancy. Drug use after the eighth month of preg- nancy is frequently associated with growth retardation, prematurity and low birth weight, and neurological

damage to the infant.25 These warnings are generaliza- tions, cutting across many categories of psychoactive substances. Health Line examines the specific risks asso- ciated with specific categories of drugs.

Approximately 26 percent of women in the United States report having smoked cigarettes in the past month during the first trimester of pregnancy; approxi- mately 18 percent report consuming alcohol, and 7 percent report binge drinking, and approximately 8 percent report smoking marijuana during this time, despite the adverse effects on early prenatal development (see Chapters 7 and 8). These past-month prevalence rates decline significantly over the second and third tri- mesters but then rise among nonpregnant women with children under three months of age, suggesting that there is a resumption in drug use among mothers in the three months after childbirth.26

Drug Abuse and HIV Infection One of the hazards associated with drug use by injection is the spread of disease when needles are shared. In the past, the contamination has primarily involved infectious hepatitis, a serious liver disease. Since the late 1970s, however, attention has turned to the potential spread of the human immunodeficiency virus (HIV) responsible for acquired immunodeficiency syndrome (AIDS). Since HIV-infected individuals may not show discernible AIDS symptoms for a considerable period of time (the median interval being ten years), there is unfortunately ample opportunity for contaminating others, either through sex- ual contact or via some direct exchange of bodily fluids.

It is estimated that about one in six injection-drug users (IDUs) in the U.S. have been infected with HIV. HIV-infection prevalence rates among IDUs exceed 40 percent, however, in at least nine other countries of the world.27 On a domestic and international level, injection-drug use remains a significant public health risk factor for the spread of HIV infection and AIDS.28

In an effort to reduce the risk of HIV infection among injecting drug users, needle-exchange pro- grams have been established so that IDUs might have the opportunity to trade in their used needles for ster- ile ones. These services are now available in thirty-eight U.S. states as well as the District of Columbia and Puerto Rico. The U.S. Department of Health and Human Services officially endorsed needle-exchange programs in 1998 as an effective part of a comprehensive strategy to reduce the incidence of HIV transmission, having estimated that needle-exchange programs can reduce new cases of HIV infection by one-third without increas- ing the use of illicit drugs. While a twenty-one-year-old

44 ■ Part One Drugs in Society/Drugs in Our Lives

Health Line Effects of Psychoactive Drugs on Pregnant Women and Newborns

In addition to the adverse effect of psychoactive drugs on fetal development and pregnancy in general, a number of such drugs carry very specific risks. Here is a review of these effects.

Alcohol • Fetal effects: Impairment in the supply of fetal oxygen

and stimulation of excess prostaglandins possibly caus- ing fetal malformations.

• Pregnancy effects: Risk of miscarriage during the sec- ond trimester of pregnancy if the mother consumed as few as one or two drinks a day.

• Newborn effects: Signs of alcohol withdrawal upon birth if the mother drank heavily. Fetal alcohol syn- drome involving retardation of postnatal growth and nervous system, abnormal craniofacial features, and numerous organ abnormalities.

Tobacco • Fetal effects: Reduced oxygen supply compounded

by carbon monoxide that interferes with the blood’s ability to carry oxygen throughout the body.

• Pregnancy effects: Increased frequency of spontaneous abortions and fetal death.

• Newborn effects: Increased risk of physical defects and lower birth weight. Also a higher risk that infants born to mothers who smoke will die before their first birthday.

Marijuana • Fetal effects: Increased carbon monoxide levels in

mother’s blood, particularly in the last trimester, result- ing in reduced oxygen in fetal blood.

• Pregnancy effects: Inconsistent findings, although there is a tendency for more males to be conceived than females if either parent is a heavy marijuana smoker.

• Newborn effects: Some evidence for abnormal sleep and arousal patterns if mother has used marijuana.

Cocaine or Crack Cocaine • Fetal effects: Constriction of blood vessels, which

reduces normal fetal blood flow and causes urogenital malformations.

• Pregnancy effects: High rates of spontaneous abortion and early separation of the placenta from the uterine wall, resulting in increased numbers of stillbirths. Increased risks of early onset of labor and preterm delivery.

• Newborn effects: Increased risk of intrauterine growth retardation: lower birth weight and smaller length and head circumference. Tendency to be jittery and easily startled. Fewer discernible withdrawal symptoms than in newborns exposed to heroin or other narcotics in utero.

Methamphetamine • Fetal effects: Unknown but likely to be similar to

effects of cocaine. • Pregnancy effects: Increased risk of premature birth,

fetal distress during delivery. • Newborn effects: Growth retardation, lethargy, increased

difficulty to arouse, and, once aroused, increased auto- nomic reactivity. Long-term effects largely unknown.

Heroin or Morphine • Fetal effects: Reduced oxygen supply to the fetus, as well

as reduced pancreatic, liver, and intestinal functioning. • Pregnancy effects: In 10 to 15 percent of pregnant

women using heroin, development of toxemia, a poi- soning of the blood between the mother and the fetus.

• Newborn effects: Retardation of intrauterine growth. Likelihood of lung problems, brain hemorrhages, and respiratory distress. Risk for perinatally transmitted HIV infection and the development of AIDS. Dramatic withdrawal symptoms usually beginning forty-eight to seventy-two hours after delivery.

Prescription Drugs • Accutane (isoretinoin): Major birth defects associated

with this antiacne medication and vitamin A derivative. • Tetracycline antibiotics: Possibility of permanent

discoloration of a child’s teeth. • Salicylates (aspirin products): Possibility of bleeding

in the mother or fetus and of delay in delivery if taken close to term or prior to delivery.

• Dilantin (phenytoin): Increased risk of heart malfor- mations, cleft lip, and mental retardation associated with this and other anticonvulsants.

• Antianxiety drugs: Possible depression of respiration in newborn when taken during labor. Fourfold increase in cleft palates and malformations of the heart and limbs when taken during early pregnancy.

• Paxil (paroxetine): Increased risk of birth defects when this antidepressant is taken during the first trimester of pregnancy.

• Barbiturates: Birth defects resembling fetal alcohol syndrome associated with long-acting barbiturates such as phenobarbital. Withdrawal symptoms in the new- born four to seven days after delivery.

Sources: Cook, P. S.; Peterson, R. C.; and Moore, D. T. (1990). Alcohol, tobacco, and other drugs may harm the unborn. Rockville, MD: Office of Substance Abuse Pre- vention. U.S. Food and Drug Administration, 2009. Smith, L. M., et al. (2008). Prenatal methamphetamine use and neonatal neurobehavioral outcome. Neurotoxicology and Teratology, 30, 20–28.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 45

ban on federal funding for needle-exchange programs was lifted in 2009, the ban was reinstated in 2011.29

Drugs, Violence, and Crime

Important questions often end up being the most compli- cated ones to answer. Consider the question of whether illicit drugs cause violence and crime. We can look at the news headlines reporting acts of social violence linked to the world of illicit drugs and the impact of those acts on our society: innocent children killed in the cross fire of rival drug gangs, thousands of crimes against individu- als and property to pay for a continuing pattern of drug abuse, terrorization of whole communities by drug deal- ers. Illicit drugs and crime are bound together in a web of greed and callous disregard for human life.

The association clearly exists. We can draw on information gained from a recently revised version of the Arrestee Drug Abuse Monitoring (ADAM) Program, known as ADAM II, conducted on an annual basis since 2007 by the U.S. Department of Justice. In ADAM II, a sampling of males who have been arrested for a serious offense in ten selected U.S. metropolitan sites (a sam- pling of regions around the country) are tested through urinalysis within 48 hours of arrest for ten major num- ber of illicit drugs.

Not surprisingly, ADAM II statistics indicate that drug use among an arrestee population is much higher than in the general U.S. population. In 2011, all cities reported a majority of arrestees testing positive for at least one of ten illicit drugs. The percentage varied, however, from 65 per- cent in Denver, Colorado and Charlotte, North Carolina to 78 percent in Sacramento, California. From 15 percent

(in Charlotte) to 37 percent (in Sacramento) of arrestees tested positive for more than one substance. Generally speaking, the substances most commonly identified at testing were, in descending order of their incidence, mari- juana, cocaine, opioids, and methamphetamine.30

ADAM II statistics confirm our suspicions about the correlation between drug use and criminal behav- ior, but do they establish a causative relationship? In other words, do drugs actually cause violent behavior and crime? If they do, which drugs have a greater responsibil- ity than others? Are illicit drugs necessarily more problem- atic with respect to violent behavior and crime than licit drugs such as alcohol? As we will see in the discussion that follows, the relationship between drugs and societal prob- lems such as violence and crime can be broken down into three specific categories: pharmacological violence, eco- nomically compulsive violence, and systemic violence.

Pharmacological Violence Pharmacological violence is an act of violence commit- ted by an offender who is under the direct influence of a psychoactive drug. The implication is that a specific drug caused violent or criminal behavior while the drug was actually present in the individual’s system. Although the ADAM II statistics reflect the fact that a large pro- portion of people have some illicit drug in their system at the time of arrest, we are unable to say whether the offense was committed as a direct result of the influence of that drug. The main criticism of evidence related to pharmacological explanations is that the detection period in a standard urinalysis test for an illicit drug can range from two to four days in the case of cocaine and from several days to two months in the case of marijuana (see Chapter 12). Therefore, testing positive for a drug at the time of arrest indicates only that the individual might have become violent or have been motivated to commit a crime while under the influence of the drug, assuming that the drug has the potential for creating a violence- producing or crime-producing effect in the first place.

In some instances, the physiological nature of the drug itself makes it quite unlikely that pharmacological violence would occur. For example, marijuana by itself, for example, makes the user more passive than active, indeed the marijuana smoker typically is quite mellow in circum- stances in which there may be some interpersonal conflict.

Mobile needle-exchange centers are available in those com- munities that permit needle-exchange programs.

pharmacological violence: Violent acts committed while under the influence of a particular psychoactive drug, with the implication that the drug caused the violence to occur.

46 ■ Part One Drugs in Society/Drugs in Our Lives

Heroin produces a passive state of mind that reduces the inclination toward violent behavior. In fact, as rates of her- oin abuse rise, the incidence of crimes against individuals (as opposed to crimes against property) declines.31

On the other hand, psychoactive stimulants such as amphetamines and cocaine or the hallucinogenic PCP (known as angel dust) produce an “on-edge” manner and a social paranoia that can be the context for violent behavior, although there is no current evidence that these drugs specifically stimulate violent behavior. Yet even in such cases, we need to be careful in the interpre- tation of studies reporting violent behavior in unselected populations. In a study conducted at an Atlanta medical center, more than half of all patients being treated for acute cocaine intoxication were reported to be aggres- sive, agitated, and paranoid just prior to and at the time of hospital admission. It is impossible to determine whether these patients were mentally unstable to begin with, prior to their taking cocaine. People who have long-standing psychological problems may be overrepre- sented in any population of cocaine abusers or of drug abusers in general.32

Crack cocaine has the dubious reputation of mak- ing the crack smoker irritable, suspicious, and inclined to lash out at another person at the slightest provoca- tion.33 Whether these effects are due to being under the influence of the drug, however, is unclear. Tendencies toward violence are observed during times of crack with- drawal as well as crack intoxication.

Of all the psychoactive drugs we could consider, the one with the most definitive and widely reported linkage to violent behavior is alcohol. In this case, the violence is clearly pharmacological, since the effects of being drunk from the ingestion of alcohol are appar- ent almost immediately. On a domestic level, males involved in spouse abuse commonly report having been drinking or having been drunk during many of the times that abuse has occurred. Moreover, violent crime outside the home is strongly related to alcohol intoxication. The more violent the crime, the greater the probability that the perpetrator of the crime was drunk while committing it. Studies show that at least a majority of sexually aggressive acts (rapes and attempted rapes) are committed while the offender is drunk (see Chapter 8).34

Does the chronic, long-term use of drugs cause individuals to engage in criminal behavior in general? There is little evidence that drugs cause an increase in one’s general inclination toward antisocial behavior. In other words, it is not true that drugs alone are capa- ble of changing the personality of the user, turning him or her from some kind of upstanding pillar of society

into a public menace. As discussed in Chapter 1, social risk factors can be identified that lead toward deviant behavior, as defined by societal norms, and that devi- ant behavior includes both drug abuse and criminal behavior. One aspect of that deviant behavior cannot be considered the cause of the other. Frequently, indi- viduals with the greatest chance of abusing drugs have a socioeconomic profile that also produces the greatest chance of criminal behavior: a low level of education or scant regard for education, a broken family, little or no social supervision, and low social status.35 As one researcher has put it,

Teenagers who begin illegal drug use are also likely to have committed other criminal acts beforehand, whether or not they have been caught. It is likely that this relationship may be sufficient to explain the higher crime rate of marijuana users. It is not so much that marijuana use causes crime (except, of course, the crime of using the drug), but that those who use marijuana are also the type of people more likely to commit criminal acts.36

Economically Compulsive Violence Economic explanations of the relationship between drug use and crime suggest that illicit drug users feel compelled to commit crimes to obtain money to buy drugs and continue a pattern of drug abuse. We can speak of the possibility of economically compulsive violence, if the violent act stems from the costliness of the drug-taking behavior.

Several studies show economic considerations to be a major component of the link between drugs and crime. A 1990 study of crack users in the Miami area showed that 59 percent participated in a total of 6,669 robberies over a twelve-month period, averag- ing thirty-one robberies per individual, or roughly one every twelve days. Yet even though the majority of these robberies were carried out to buy drugs, we cannot assume that they all involved the classic pic- ture of break-ins and holdups. A large percentage involved the theft of drugs from drug dealers or other users, or the users themselves being victims of a drug robbery.37 Nonetheless, a large proportion of the crimes committed to obtain drug money involved violent acts directed toward individuals within the

economically compulsive violence: Violent acts that are committed by a drug abuser to secure money to buy drugs.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 47

community. Particular targets included store- keepers, children, and the elderly.

When robbery is the means for financing drug abuse, the extent of this crime has been shown to be closely related to market conditions at the time. When heroin prices are high, for example, the level of property crime goes up; when heroin prices are low, the crime level goes down. In other words, heroin abusers steal more to maintain a stable consumption of heroin if the drug becomes more expensive to obtain. Therefore, deliber- ate elevation of drug prices, when accomplished by reducing the supply, not only fails to reduce the incidence of abuse but also tends to increase the incidence of criminal behavior among drug abusers.37

The type of crime a drug user commits under these circumstances is typically related to gender. Males are more likely to commit crimes against persons (muggings) and property (burglary, car theft) or violate drug laws (illicit drug distribu- tion and trafficking), whereas females are more likely to commit crimes against the public order, such as prostitution. One study, for example, found that 64 percent of female crack users exchanged sex for money to buy drugs and that 24 percent reported trading sex for drugs. Among women who bartered sex for crack cocaine, many of them would remain in the “crack houses” for extended periods of time, provid- ing sexual favors to multiple customers to secure a continuous supply of the drug.38

Systemic Violence A third important source of social violence and criminal behavior is inherent within the drug world itself. A sub- stantial number of drug users, as their drug use becomes more intense, involve themselves in drug distribution and a criminal subculture that uses violence as a means of maintaining control over its “business.”

Researchers use the term systemic violence to refer to the violence that arises from characteristic features of drug dealing (Figure 2.5). Systemic violence can result from such situations as territorial disputes over illicit drug distribution, the consequences of selling inferior grades of the illicit drug, or fraudulent handling of funds from drug sales (referred to as “messing up the money”).

The best illustrations of systemic violence can be seen in the behavior of two categories of gangs: (1) outlaw motorcycle gangs primarily in Western U.S. states, nota- bly the Hell’s Angels, the Outlaws, the Bandidos, and the Pagans, and (2) street gangs in urban communi- ties, such as the Crips and the Bloods in Los Angeles. Since the late 1980s, law enforcement authorities as well as researchers have recognized both organizations as having become the “new faces of organized crime” in America.39

In contrast to the popular image of mythic figures rebelling against the norms of society or misunderstood social misfits, members of outlaw motorcycle gangs typically have a history of violent behavior and criminal records that include offenses such as drug trafficking, racketeering, brawling, weapons possession, and homi- cide. Traditionally, outlaw motorcycle gangs have been principal dealers and traffickers of methamphetamine. In fact, methamphetamine is often referred to as “crank” because motorcyclists would hide the drug in the crank- shafts of their motorcycles. While their association with methamphetamine continues today, their present-day

F i g u r e 2 . 5

The tripartite framework: Three aspects of drugs and violence.

Source: Goldstein, P. (1985, Fall). The drug-violence nexus: A tripartite framework. Journal of Drug Issues, 493–506.

The Drug–Violence

Connection

Pharmacological violence

Violent behavior committed while under the in uence of a speci c psychoactive drug, with the implication that the drug was responsible

Economically compulsive violence

Violent criminal activity (e.g., robbery) motivated by the need for money to buy drugs

Systemic violence

Violent acts in the course of enforcing discipline within an illicit drug distribution network, settling territorial disputes between rival drug dealers, or punishing police informants

systemic violence: Violence that arises from the traditionally aggressive patterns of behavior within a network of illicit drug trafficking and distribution.

48 ■ Part One Drugs in Society/Drugs in Our Lives

drug involvement has been documented as extending to trafficking in marijuana, cocaine, and PCP.40

The association between street gangs and systemic violence became particularly striking in the 1980s dur- ing the height of crack cocaine abuse in inner-city neighborhoods. In contrast to outlaw motorcycle gangs, the largest proportion of street gangs involved in drug sales during this time were comprised of individu- als between 15 and 16 years of age. The prevalence of gang members aged 18 years or older increased when drug sales reached higher levels. White and Hispanic/ Latino gang members tended to be more prevalent in neighborhoods where drug involvement is relatively low, and African American gang members tended to be more prevalent in neighborhoods where drug involve- ment is high. The extreme levels of systemic violence during this period were attributed in large part to the drug distribution activities of street gang members and their leaders.41

The question of which factor causes the other cannot be easily answered. It is quite possible that a combination of self-selection and modeling behav- ior is occurring here. Inherently violent individu- als may be useful in maintaining tight discipline in groups that focus on drug taking and drug selling; they may be useful as combatants in territorial disputes in general.42

Given the link between the distribution of crack cocaine and systemic violence, particularly as pertain- ing to street gangs, it should not be surprising that a decline in the prevalence of crack abuse, first observed in the latter part of the 1990s, would be accompa- nied by a decline in homicide rates and violent crime in the areas where crack abuse had been dominant. Community-based policing procedures focused on breaking up drug gangs and large street-level drug mar- kets, thereby changing the pattern of drug buying and selling. An expert in the area of criminal justice has put it this way:

In addressing the connections between drug-taking behavior and crime, it is important to include patterns of criminal behavior that are associated with affluent populations as well as impoverished ones. The spread of illicit drug dependence to higher socioeconomic levels of society, since the 1970s, has led to an increase in white-collar crimes of fraud and embezzlement that are motivated by the need for drug money. In such cases, we are speaking of economically compulsive acts. Though generally nonviolent in nature, these crimi- nal acts involve substantially greater amounts of lost revenue than the burglaries and robberies common to poorer neighborhoods.

Governmental Policy, Regulation, and Laws

How should we as a society respond to the social prob- lems of drug-taking behavior? We are faced with an overwhelming flood of illicit drugs entering the United States from around the world, only a small fraction of which are ever identified, much less confiscated, despite the well-publicized drug seizures.43

We can express our moral outrage that the situation has become so bad, that drug abuse is costing society such huge amounts of money and wasting so many lives. Social despair is so well entrenched in some portions of society that solutions seem to be nonexistent. The offi- cial responses that U.S. society has made through its his- tory, in terms of regulatory controls over drugs, can be understood more clearly in terms of its attitudes toward drug-taking behavior and drug users than in terms of the drugs themselves.

Efforts to Regulate Drugs, 1900–1970 Until about 1900 in the United States, the govern- mental attitude toward addictive behavior was one of laissez-faire, roughly translated as “allow [people] to do as they please,” which meant there was little regulation or control. It was a well-ingrained philos- ophy, going back to our early days as a nation, that government should stay out of the lives of its citizens. Nonmedical use of morphine, for example, was not considered respectable, and in some circles was seen as immoral, but it was no more disreputable than heavy drinking.44

Prior to the twentieth century, there were move- ments to ban alcoholic consumption but none to ban the wholesale use of opium, morphine, heroin, or cocaine. The only exception was the strong opposition to the smoking of opium, an attitude directed princi- pally toward Chinese immigrants in the western states, as noted in Chapter 1. By the turn of the century, however, a wave of reform sentiment began to sweep the country. In 1905, the popular magazine Collier’s uncovered the fraudulent claims and improper label- ing of patent medicines that contained large amounts of alcohol, opium, morphine, and cocaine. Large- scale abuses in the meatpacking industry, publicized

laissez-faire (LAY-say FAIr) (Fr.): The philosophy of exerting as little governmental control and regulation as possible.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 49

in 1906 in Upton Sinclair’s novel The Jungle, turned the stomach of the American public and quickly pres- sured President Theodore Roosevelt and Congress to take action.

The result was enactment of the Pure Food and Drug Act. This 1906 law required that food and drug manufacturers list the amounts of alcohol or “habit- forming” drugs, specified as any opium-related drug or cocaine, on the label of the product, but the sale and the use of any of these substances were left unrestricted. The law was the first of a series of legislative controls over food, drinks, drugs, and eventually cosmetics. As Chapter 14 will describe, this legislation eventually evolved into the establishment of the present-day U.S. Food and Drug Administration.

The second major piece of legislation in the early part of the century was the Harrison Act of 1914. This new law concerned itself with opium- related drugs (defined as narcotics) and cocaine. The law was designed to regulate drug abuse essentially through a process of governmental taxation. The act required anyone importing, manufacturing, selling, or dispensing these drugs to register with the Treasury Department, pay a special tax, and keep records of all transactions. From a constitutional perspective, the Harrison Act was a tax law, similar to laws regulating the sale of alcohol. As you can imagine, the difficul- ties in abiding by the law would soon become virtually insurmountable. Drug-taking behavior that involved these drugs was now driven, from a societal point of view, underground.

Under the Harrison Act, opium, morphine, and heroin were defined as “narcotics,” but cocaine was not. Nonetheless, cocaine was often referred to as a narcotic as well, despite the fact that cocaine has totally different psychological and physiological properties (see Chapter 4). Making matters worse, in the years after the enactment of the Harrison Act, several restricted drugs, including marijuana and the hallucinogenic peyote, were also referred to as narcotics without regard to their pharmacological or psychological characteristics. Today, many people still think of any illegal drug as a narcotic, and for many years the bureau at the Treasury Department charged with drug-enforcement respon- sibilities was called the Federal Bureau of Narcotics (FBN), and its agents were known on the street as “narks.”

By 1933, as the Prohibition Era ended, the atten- tion of drug-enforcement policymakers, led by Harry Anslinger, the newly installed FBN director, turned from the control of alcohol consumption to the publicizing of marijuana as a major public menace. Congressional

committees heard testimony from police claiming that marijuana, now called the “killer weed,” aroused people to commit all sorts of violent crime. Movies produced and released in the 1930s, such as Reefer Madness (now a cult classic) and Marihuana: Weed with Roots in Hell, depicted the moral slide of supposedly innocent young people after they were introduced to marijuana. The result was the Marijuana Tax Act of 1937, after which growers, sellers, and buyers of marijuana were subject to tax. State laws made possession of marijuana illegal (see Chapter 7).

The 1960s saw a number of amendments to the enforcement laws then in effect, as new drugs of abuse came onto the scene. The Federal Bureau of Narcotics became the Federal Bureau of Narcotics and Dangerous Drugs, and Anslinger, whose tenure as director rivaled that of FBI director J. Edgar Hoover in longevity and power, retired in 1962.

Rethinking the Approach toward Drug Regulation, 1970–Present The Comprehensive Drug Abuse Prevention and Control Act of 1970 organized the control of drugs under five classifications called schedules of controlled substances, based on their potential for abuse (see Table 2.2). Since 1970, these categories have defined the extent to which various drugs are authorized to be available to the general public in the United States. Schedules I and II refer to drugs presenting the highest level of abuse potential, and Schedule V refers to drugs presenting the least. All drugs, except those included under Schedule I, are legally available on either a pre- scription or an over-the-counter basis.

Under the system establishing schedules of con- trolled substances, drugs that are considered more dangerous and more easily abused are subject to pro- gressively more stringent restrictions on their posses- sion, the number of prescriptions that can be made, or the manner in which they can be dispensed. In the case of Schedule I drugs (heroin, LSD, mescaline, and marijuana, for example), no acceptable medical use has been authorized by the U.S. government, and availabil- ity of these drugs is limited to research purposes. The federal penalties for possession and sale of Schedule I drugs, as well as those for violating the restrictions set for other controlled substances, will be examined in Chapter 17.

The 1970 law shifted the responsibility of drug enforcement from the Treasury Department to the Justice Department, ending the long era of attempts

50 ■ Part One Drugs in Society/Drugs in Our Lives

to regulate drug-taking behavior through taxation. As prevention and treatment programs for drug abuse were set up and funds were allocated for educational material, the emphasis started to shift from penalties on the drug user to penalties on drug dealing. In 1988, the Anti-Drug Abuse Act imposed penalties for money laundering when associated with drug smuggling and sales. Under this act, a new cabinet-level position, a “drug czar,” was established to coordinate the efforts of the many federal agencies and departments that were by now involved in drug regulation and drug-law enforcement. Overall strategic planning and imple- mentation of drug policy in the United States now orig- inates from the White House Office of National Drug Control Policy.

Drug Law Enforcement and Global Politics

The enforcement picture today is far more complex than it was a few decades ago, when the focus was chiefly on the “supply” side (the availability of drugs) of the problem, without much consideration of the “demand” side (the dependence of individuals on drugs capable of being abused). Treatment and prevention programs in the 1980s represented only 30 percent of the federal budget allocated to controlling drug abuse. More recently, the amount allotted to treatment and prevention has increased somewhat, but about 60 per- cent of funds in the $25.6 billion drug-control budget are still directed toward efforts to reduce the supply of illicit drugs.45

A large proportion of the drug-control budget, approximately $6 billion annually, is expended inter- nationally and at our borders to hold back the continu- ing influx of illicit drugs into the country. The primary federal agencies involved in this effort are the Drug Enforcement Administration (DEA), the U.S. Customs and Border Patrol Agency, the U.S. Coast Guard and other branches of the U.S. military, and the Immigration and Naturalization Service (INS). In addition, govern- ment agents are stationed in more than forty foreign countries, working with the Department of Defense and the Department of State, to limit the exportation of illicit drugs at the source (Portrait).

In recent years, however, our attempts to stem the flood of illicit drugs into the United States have been complicated by a number of economic and

TAbLE 2.2

The five schedules of controlled substances in the Comprehensive Drug Abuse Prevention and Control Act

SCHEDuLE I

High potential for abuse. No accepted medical use. Research use only; separate records must be maintained, and the drugs must be stored in secure vaults.

Examples: heroin, LSD, mescaline, marijuana, PCP

SCHEDuLE II

High potential for abuse. Some accepted medical use, though use may lead to severe physical or psychologi- cal dependence. Prescriptions must be written in ink, or typewritten, and signed by a medical practitioner. Verbal prescriptions must be confirmed in writing within 72 hours and may be given only in a genuine emer- gency. No prescription renewals are permitted. Separate records must be maintained, and the drugs must be stored in secure vaults.

Examples: codeine, morphine, cocaine, methadone, amphetamines, short-acting barbiturates

SCHEDuLE III

Some potential for abuse. Accepted medical use, though use may lead to low-to-moderate physical dependence or high psychological dependence. Pre- scriptions may be oral or written. Up to five prescription renewals are permitted within 6 months.

Examples: long-acting barbiturates, narcotic solutions (for example, paregoric or tincture of opium in alcohol) or mixtures (for example, 1.8% codeine)

SCHEDuLE IV

Low potential for abuse. Accepted medical use. Pre- scriptions may be oral or written. Up to five prescription renewals are permitted within 6 months.

Examples: antianxiety drugs and sedative-hypnotics (for example, Valium and Klonopin)

SCHEDuLE V

Minimal abuse potential. Widespread medical use. Minimal controls for selling and dispensing.

Examples: prescription cough medicines not containing codeine, laxatives

Source: Drug Enforcement Administration, U.S. Department of Justice, Washington, DC.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 51

itself, but also as a source of marijuana, metham- phetamine, and illegal prescription medications (Figure 2.6). An escalation of violence among rival Mexican drug traffickers has engulfed that country and spilled over into U.S. border towns.46 Efforts to

political factors on a global scale. Despite its status as a principal U.S. trading partner, the country of Mexico, immediately to our south, remains a major drug-trafficking route not only for cocaine from South America and heroin originating from Mexico

p o r T r A I T Pablo Escobar—Formerly Known as the Colombian King of Cocaine

Pablo Escobar, one of the most powerful, profitable, and violent organized crime bosses in history, began his career as a small-time crimi- nal in the slums of Medellin, Colom- bia. At age twenty-six, Escobar was arrested for possession of thirty-nine pounds of cocaine, his first and only drug bust. He was never tried for the crime; the arresting officer was mys- teriously murdered, and nine judges refused to hear the case because of death threats.

The infamous Medellin Cartel, created by Escobar, would become the first modern-day cocaine trafficking alliance. Organized along the lines of a large corporation, the cartel was ver- tically integrated and controlled virtu- ally all aspects of the cocaine business from manufacturing and smuggling to wholesale distribution of cocaine in the United States. Escobar’s election to the Colombian Congress in 1982 gave him immunity from arrest. But not long after, he came to realize that more power in Colombia could be gained through violence and bribes than through politics.

By 1984, Escobar had controlled over 80 percent of the Colombian drug trade, and it was estimated that Escobar himself was making over $2.75 billion a year. He had “earned” a place on the Forbes magazine list of the wealthiest people in the world. Projecting himself as “a man of the people,” Escobar built housing for the poor, schools, hospitals, and even a soccer stadium.

Despite the cultivated image of Robin Hood, however, was a man

Central Intelligence Agency (CIA), and agents of the Drug Enforcement Administration (DEA). In 1993, authorities finally caught up with him. In a final confrontation, a barrage of gunfire ended his life.

Within months of Escobar’s death, the Cali Cartel, a long-standing rival to the Medellin Cartel, had taken over the cocaine business in Colombia. But its newfound dominance was soon to end. Cali Cartel leaders were arrested in Colombia in 1997 and later extra- dited to the United States. In 2006, a plea agreement included a judgment of forfeiture in the amount of $2.1 billion to be levied against Cali Cartel narcotic-related assets as well as busi- nesses around the world.

Today, cocaine trafficking is controlled by more than 300 “mini- cartels” in the Andean region in as- sociation with criminal organizations in Mexico, where approximately 72 percent of cocaine available in U.S. is transported.

Sources: Brooke, J. (1990, June 7). In the capital of cocaine, savagery is the habit. New York Times, p. 4. Drug Enforcement Administration (2006, September 26). Cali cartel leaders plead guilty to drug and money laundering conspiracy charges. News release. Washington, DC: U.S. Department of Justice. Fedarko, K. (1993, December 13). Escobar’s dead end. Time, p. 46. Lyman, M. D., and Potter, G. W. (2000). Organized crime. Upper Saddle River, NJ: Prentice Hall. Watson, R., and Katel, P. (1993, December 13). Death on the spot: The end of a drug king. Newsweek, pp. 18–21.

intent on using violence and assassination to maintain his

power and the cartel’s domination over the life of Colombia. The nation would come to resemble an armed camp. Police officers, judges, public officials, and journalists were in con- stant fear of being assassinated. Public bombings and drive-by shootings were common occurrences. Escobar himself is alleged to have been behind the murder of three presidential candi- dates, a Colombian attorney general, more than 200 judges, 100 police officers, and dozens of journalists. He is alleged to have been responsible for the bombing of a Colombian jetliner, resulting in 107 deaths. In 1990, Escobar offered a bounty of $4,000 for each police officer killed in Colombia. During the following month, 42 city police officers were murdered.

In a desperate response to this reign of terror, the Colombian gov- ernment offered drug traffickers im- munity from extradition to the United States if they surrendered themselves to authorities. The traffickers were promised shorter prison terms in Colombia itself.

In 1991, at the age of forty-one, Pablo Escobar turned himself in, having agreed to be placed in a specially built Colombian prison. However, it was a prison that evidently was not secure enough to hold him imprisoned for long. Within months, Escobar escaped, and in one of the most famous manhunts in history, Escobar managed for a while to elude search teams comprised of an elite Colombian police commando squad, members of the U.S.

52 ■ Part One Drugs in Society/Drugs in Our Lives

reduce the cultivation of opium in the rugged, moun- tainous areas of Afghanistan, presently the supplier of approximately 94 percent of the world’s supply of heroin, have been intertwined with efforts to control the political influence of regional warlords, whether they have terrorist associations or not. The intercon- nected and sometimes opposing goals of America’s drug-control policy and global foreign policy con- tinue to be a major challenge in the effort to regulate drug-taking behavior both in the United States and around the world.47

We are more than 40 years into the “war on drugs” declared officially by President Nixon in 1971; the price tag for this war has exceeded $400 billion. Each year more money is requested to carry on the fight, but the struggle continues to be frustrating in the extreme, and the nation grows increasingly battle-weary

(see Point/Counterpoint I, pages 58–59). Although the expenditures are up by more than 1,400 percent since 1981, there is no clear-cut correlation between budget allocations from year to year and the avail- ability of illicit drugs. Many experts in the field of drug abuse view the solution not to be in foreign countries, at U.S. borders, or in U.S. prisons, but to be in the communities of the United States. A recom- mendation gaining increasing support would shift the emphasis from “use reduction” to “harm reduction,” acknowledging that drugs may never be absent from our society (Health Line).48

The public policy issues surrounding the “demand” side of the drug-abuse equation, particularly as it per- tains to prevention and treatment, will be considered in greater detail in Chapter 16 (see the Portrait on page 384) and Chapter 17.

European shipments of drugs to the U.S.

Cocaine Marijuana

MDMA

Heroin

Distribution Command & Control

Methamphetamine

Chicago

New York

Houston

Phoenix

Atlanta

San Diego

Los Angeles

Seattle

Pseudoephedrine shipped to Mexican super-labs from China

PRODUCED IN THE U.S. Marijuana

Methamphetamine MDMA

Other Synthetic Drugs

South American Southeast Asian Southwest Asian

Miami

F I g u r E 2 . 6

Drug smuggling entry points into the United States for cocaine, marijuana, heroin, MDMA (Ecstasy), and methamphetamine. Much of the entry from Mexico originates in Colombia and other South American countries.

Source: Drug Enforcement Administration (2011). FY 2012 Performance budget congressional submission. Washington, DC: Drug Enforcement Administration, U.S. Department of Justice, p. 12.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 53

Members of the U.S. Coast Guard law enforcement team gather in Miami around more than 5,000 pounds of cocaine seized from a Honduran fishing boat off the coast of Colom- bia. The drugs were discovered hidden in compartments within the fuel tank, and eight Colombians were arrested. The 110-foot boat was later towed to Miami and confiscated.

Health Line Harm Reduction as a National Drug-Abuse Policy

To say that we are waging a “war on drugs” is, in effect, communicating how serious we are in dealing with the problems of drug abuse in the United States. Using the metaphor of warfare, we recognize that there is an ac- knowledged enemy (drug misuse and abuse), there are victims or casualties (us), there are resources at our dis- posal to fight the necessary battles (federal and state gov- ernments, communities, parents, etc.), and there is a high price to pay (billions of dollars of federal funds each year).

The implications of this real-life struggle, such as our overall strategy and ultimate goals, are also drawn in metaphorical terms. Do we want total victory and com- plete annihilation of the enemy? Or do we want some kind of negotiated settlement, some type of compromise that gives us a semblance of peace and tranquility? If it is the former, then we require a total elimination of abu- sive drug-taking behavior in America, often expressed as “zero tolerance.” If it is the latter, then we require a good

deal less. We desire, in that case, only a reduction of the harmful consequences of abusive drug-taking behavior, knowing full well that total elimination is unrealistic and perhaps unattainable. The second alternative is referred to as the harm reduction approach. Whether we should choose a harm reduction or a zero tolerance approach is at the core of our debate on a national drug-abuse policy.

The harm reduction approach in drug policy has its his- torical roots in the libertarian philosophy of the nineteenth- century philosopher John Stuart Mill, who argued that the state (i.e., the government) did not have the duty to protect individual citizens from harming themselves. As Mill expressed it,

The only purpose for which power can be rightfully executed over any member of a civilized community, against his will, is to prevent harm to others. His own good, either physical or moral, is not a sufficient warrant. . . . Over himself, over his own body and mind, the individual is sovereign.

(Continued)

54 ■ Part One Drugs in Society/Drugs in Our Lives

It is readily evident, however, that drug-taking behavior does indeed harm other people. The question, according to those advocating a harm reduction strategy, is to look for policies that reduce the harm that drugs do, both di- rectly to the drug user and indirectly to others.

Examples of the harm reduction approach include needle-exchange programs to lower the incidence of HIV infection among intravenous drug abusers, methadone maintenance programs for the treatment of heroin abusers (see Chapter 5), efforts to reduce the incidence of driving while under the influence of alcohol (see Chapter 8), and the use of nicotine patches to avoid the adverse health ef- fects of cigarette smoking on the smoker and those around the smoker (see Chapter 10). A more controversial appli- cation of the harm reduction approach is the suggestion

that we attempt to reduce an individual’s heavy drug use down to a level of occasional use, rather than no use at all.

Sources: Denning, P.; Little, J.; and Glickman, A. (2003). Over the influence: The harm reduction guide for manag- ing drugs and alcohol. New York: Guilford Press. How did we get here? History has a habit of repeating itself (2001, July 28–August 3). Economist, pp. 4–5. Quotation of John Stuart Mill on page 5. Levinthal, C. F. (2003). Question: Should harm reduction be our overall goal in fighting drug abuse? Point/Counterpoint: Opposing perspectives on issues of drug policy. Boston: Allyn and Bacon, pp. 70–73. Marlatt, G. A. (Ed.) (2002). Harm reduction: Pragmatic strategies for managing high-risk behaviors. New York: Guilford Press.

Summary

Drug Toxicity ● A drug’s harmful effects are referred to as its toxicity.

Acute toxicity can be measured in terms of either a drug’s therapeutic index or its margin of safety, each of which can be computed from its effective dose-re- sponse and lethal dose-response curves.

The DAWN reports ● Drug Abuse Warning Network (DAWN) statistics,

which reflect drug-related lethal and nonlethal emer- gencies in major metropolitan hospitals in the United States, offer another measure of acute drug toxicity. In general, DAWN statistics show that cocaine and narcotic drugs are both highly toxic and that many emergencies involve drugs being taken in combina- tion with alcohol. There are also recent concerns about the increasing number of emergencies associ- ated with club drugs and opioid pain medications.

behavioral Tolerance and Drug overdose ● A tolerance effect is the capacity of a drug to have a

gradually diminished effect over repeated adminis- trations; in effect, a greater dose has to be taken to maintain the original effect of the drug. Tolerance effects can be quite dangerous, because experienced drug users often end up taking potentially lethal dose levels.

● The setting within which drug-taking behavior occurs is an important factor in behavioral tolerance. Behav- ioral tolerance effects are based on the principles of Pavlovian conditioning.

physical and psychological Dependence ● Drugs can be viewed in terms of a physical depen-

dence model, in which the compulsive drug-taking behavior is tied to an avoidance of withdrawal symp- toms, or a psychological dependence model, in which the drug-taking behavior is tied to a genuine craving for the drug and its highly reinforcing effects on the user’s body and mind.

psychiatric Definitions ● The American Psychiatric Association currently

recognizes two major conditions associated with drug-taking behavior: substance dependence and sub- stance abuse. The broader term “substance” is used instead of “drug,” because there is often confusion in the public mind about what is defined as a drug and what is not.

Special Circumstances in Drug Abuse ● Increasing attention has been directed toward the

harmful effects that drug abuse has on pregnant women, in terms of problems both with the pregnancy itself and with the neural development of the fetus.

● There is also concern about the increased risk of HIV infection (and the spread of AIDS) among intrave- nous drug users when needles are shared.

Drugs, Violence, and Crime ● There is an overall association between the taking of

illicit drugs and crime, but careful analysis indicates that the drug with the closest connection to social vio- lence is alcohol, and that heroin and marijuana cause

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 55

the user to be less inclined toward violent behavior rather than more so.

● It is clear that drug abuse prompts many drug users to commit criminal acts (generally property theft) to support the drug habit. It is also clear that there is a considerable violence inherent in the trafficking and distribution of illicit drugs, through the criminal be- havior of outlaw motorcycle gangs and street gangs in urban communities.

governmental policy, regulation, and Laws ● Since the beginning of the twentieth century, U.S.

society’s philosophy toward drug-taking behavior has been that we should restrict it by reducing the avail- ability of illicit drugs and making it as difficult as possible for the potential drug user to engage in drug- taking behavior.

● The Harrison Act of 1914 was the first of several leg- islative efforts to impose criminal penalties for the use of opioids (principally heroin) and cocaine and eventually the use of marijuana, hallucinogens, and several other types of psychoactive drugs.

● The Comprehensive Drug Act of 1970 organized the federal control of drugs under five classifications called schedules. Overall planning and implementa- tion of drug policy in the United States now origi- nate from the White House Office of Drug Control Policy.

Enforcement of Drug Laws on a global Scale ● Today’s drug-law-enforcement program in the

United States places considerable emphasis on the interdiction of drugs entering the country and less emphasis on the treatment and prevention of drug abuse.

● Attempts to reduce the influx of illicit drugs into the United States are complicated by a series of economic and political factors on a global scale, particularly with respect to international relations with nations such as Mexico and Afghanistan that have been involved either in drug cultivation or in trafficking. The inter- twining and sometimes opposing goals of America’s drug-control policy and global foreign policy continue to be a major challenge.

Key Terms

acute toxicity, p. 30 behavioral tolerance, p. 37 catheter, p. 40 chronic toxicity, p. 36 dose, p. 30 dose–response curve, p. 30 Drug Abuse Warning

Network (DAWN), p. 33

drug-related ED visit, p. 33

economically compulsive violence, p. 46

effective dose (ED), p. 30 laissez-faire, p. 48 lethal dose (LD), p. 30 margin of safety, p. 31

pharmacological violence, p. 45

physical dependence, p. 39

polydrug use, p. 33 psychological dependence,

p. 40 substance abuse, p. 41

substance dependence, p. 41

substance use disorder, p. 41

systemic violence, p. 47 therapeutic index, p. 30 tolerance, p. 37 toxicity, p. 30

Endnotes

1. The Gallup Organization (2005, April 5). Drug use still among Americans’ top worries. Gallup Organization, Princeton, NJ. The Gallup Organization (2007, October 19). Little change in public’s view of the U.S. drug prob- lem. Gallup Organization, Princeton, NJ. Kleiman, M. A. R.; Caulkins, J. P; Hawken, A. (2011). Drugs and drug policy: What everyone needs to know. New York: Oxford University Press.

2. Harwood, H. (2011, October 23). Recent findings on the economic impacts of substance abuse. Presented at the American Psychological Association 2011 Science Leadership Conference, Psychological Science and Sub- stance Abuse, Washington, DC.

3. Cummings, N. A. (1979). Turning bread into stone: Our modern antimiracle. American Psychologist, 34, 1119–1129.

4. Treaster, J. B., and Holloway, L. (1994, September 4). Potent new blend of heroin ends eight very different lives. New York Times, pp. 1, 37.

5. Substance Abuse and Mental Health Services Adminis- tration (2013). Drug Abuse Warning Network: National estimates of drug-related emergency department visits 2004–2011. Rockville, MD: Substance Abuse and Mental Health Services Administration, Excel files. Sub- stance Abuse and Mental Health Services Administration (2012). Drug Abuse Warning Network, 2010: Area pro- files of drug related mortality. Rockville, MD: Substance Abuse and Mental Health Services Administration.

6. Substance Abuse (2013), Drug Abuse Warning Network, National estimates. Excel files.

7. Ibid.

56 ■ Part One Drugs in Society/Drugs in Our Lives

8. Ibid. 9. Substance Abuse, Area profiles of drug-related mortality,

pp. 59–60 and 67–68. 10. Centers for Disease Control and Prevention (2012, July).

Prescription painkiller overdoses. Atlanta, GA: Centers for Disease Control and Prevention. Centers for Disease Control and Prevention (2011, November). Prescription painkiller overdoses in the US. Atlanta, GA: Centers for Disease Control and Prevention.

11. Lankester, E. R. (1889). Mithridatism. Nature, 40, 149. 12. Siegel, S. (1990). Drug anticipation and the treatment

of dependence. In B. A. Ray (Ed.), Learning factors in substance abuse (NIDA Research Monograph 84). Rock- ville, MD: National Institute on Drug Abuse, pp. 1–24.

13. Gerevich, J.; Bácskai, E.; Farkas, L.; and Danics, Z. (2005). A case report: Pavlovian conditioning as a risk factor of heroin “overdose” death. Harm Reduction Journal, 2. Siegel, S. (1975). Evidence from rats that morphine tolerance is a learned response. Journal of Comparative and Physiological Psychology, 89, 489–506.

14. Brecher, E. M., and the editors of Consumer Reports. (1972). Licit and illicit drugs. Mount Vernon, NY: Consumers Union.

15. Siegel, S. (1999). Drug anticipation and drug addiction. The 1998 H. David Archibald Lecture. Addiction, 94, 1113–1124.

16. Jaffe, J. H. (1985). Drug addiction and drug abuse. In A. G. Gilman, L. S. Goodman, T. W. Rall, and F. Murad (Eds.), The pharmacological basis of therapeutics. New York: Macmillan, pp. 532–581.

17. Blum, K. (1991). Alcohol and the addictive brain. New York: Free Press, p. 17.

18. Pinel, J. P. J. (2003). Biopsychology (5th ed.). Boston: Allyn and Bacon, p. 398.

19. Shalev, U.; Grimm, J.W.; and Shaham, Y. (2002). Neu- robiology of relapse to heroin and cocaine seeking: A review. Pharmacological Reviews, 54, 1–42.

20. Pickens, R., and Thompson, T. (1968). Cocaine-reinforced behavior in rats: Effects of reinforcement magnitude and fixed-ratio size. Journal of Pharmacology and Experimental Therapeutics, 161, 122–129.

21. Hoffmeister, F. H., and Wuttke, W. (1975). Psychotropic drugs as negative reinforcers. Pharmacological Reviews, 27, 419–428. Yokel, R. A. (1987). Intravenous self-administration: Response rates, the effect of pharma- cological challenges and drug preferences. In Michael A. Bozarth (Ed.), Methods of assessing the reinforcing properties of abused drugs. New York: Springer-Verlag, pp. 1–34.

22. Johanson, C. E. (1984). Assessment of the abuse potential of cocaine in animals. In J. Grabowski (Ed.), Cocaine: Pharmacology, effects, and treatment of abuse. Rockville, MD: National Institute on Drug Abuse, pp. 54–71.

23. Quotation from Goode, E. (1999). Drugs in American society (5th ed.). New York: McGraw-Hill, p. 47. Data from Bozarth, M.A., and Wise, R.A. (1985). Toxicity

associated with long-term intravenous heroin and cocaine self-administration in the rat. Journal of the American Medical Association, 254, 81–83.

24. American Psychiatric Association (2013). Diagnostic and statistical manual (5th ed.). Washington, DC: American Psychiatric Association. American Psychiatric Associa- tion (2000). Diagnostic and statistical manual, Text Revi- sion (4th ed.). Washington, DC: American Psychiatric Association, pp. 191, 197, and 199.

25. Cook, P. S.; Petersen, R. C.; and Moore, D. T. (1990). Alcohol, tobacco, and other drugs may harm the unborn. Washington, DC: Office of Substance Abuse Prevention.

26. Substance Abuse and Mental Health Services Admin- istration (2009, May 21). Substance use among women during pregnancy and following childbirth. The NSDUH Report,1–4. Substance Abuse and Mental Health Services Administration (2012). Results from the 2011 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Administration, Tables 6.73B, 6.75B, 6.76B, and 6.77B.

27. Mathers, B. M.; Degenhardt, L.; Phillips, B.; Wiessing, L., et al. (2008). Global epidemiology of injecting drug use and HIV among people who inject drugs: A system- atic review. Lancet, 372, 1733–1745.

28. Centers for Disease Control and Prevention (2011, June 24). HIV surveillance in injection drug users. Atlanta, GA: Centers for Disease Control and Prevention.

29. An agreement on spending; Editorial (2011, Decem- ber 17). New York Times, p. A24. Righting a wrong, much too late: Editorial (2009, December 26). New York Times, p. A22. Centers for Disease Control and Prevention (2010, November 19). Syringe exchange programs—United States 2008. Morbidity and Mortality Weekly Report, 59, 1488–1491.

30. Office of National Drug Control Policy (2012, May) ADAM II 2011 annual report. Arrestee Drug Abuse Moni- toring Program II. Washington, DC: Office of National Drug Control Policy, Executive Office of the President, Appendix C.

31. De La Rosa, M.; Lambert, E. Y.; and Gropper, B. (1990). Introduction: Exploring the substance abuse–violence connection. In Drugs and violence: Causes, correlates, and consequences (NIDA Research Monograph 103). Rock- ville, MD: National Institute on Drug Abuse, pp. 1–7.

32. Roth, J. A. (1994, February). Psychoactive substances and violence: Research brief. Washington, DC: National Institute of Justice. Tyner, E. A., and Fremouw, W. J. (2008). The relation of methamphetamine use and vio- lence: A critical review. Aggression and Violent Behavior, 13, 285–297.

33. Gold, M. S. (1991). The good news about drugs and alcohol: Curing, treating and preventing substance abuse in the new age of biopsychiatry. New York: Villard Books.

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 57

34. Bureau of Justice Statistics (2010, September). Alcohol and crime: Data from 2002 to 2008. Washington, DC: U.S. Department of Justice, Table 29. Bushman, B. J. (1993, October). Human aggression while under the influence of alcohol and other drugs: An integrative research review. Current Directions in Psychological Sci- ence, pp. 148–152. Foran, H. M., and O’Leary, K. D. (2008). Alcohol and intimate partner violence: A meta- analytic review. Clinical Psychology Review, 28, 1222– 1234. Kuhns, J. B., and Clodfelter, T. A. (2009). Illicit drug-related psychopharmacological violence: The cur- rent understanding within a causal context. Aggression and Violent Behavior, 14, 69–78. Mohler-Kuo, M.; Dowdall, G. W.; Koss, M. P.; and Wechsler, H. (2004). Correlates of rape while intoxicated in a national sample of college women. Journal of Studies on Alcohol, 65, 37–45.

35. Galea, S.; Nandi, A.; and Vlahov, D. (2004). The social epidemiology of substance use. Epidemiologic Reviews, 26, 36–52.

36. Inciardi, J. A. (1990). The crack–violence connection within a population of hard-core adolescent offenders. In M. De La Rosa, E. Y. Lambert, and B. Gropper (Eds.), Drugs and violence: Causes, correlates, and consequences (NIDA Research Monograph 103). Rockville, MD: National Institute on Drug Abuse, pp. 92–111. Quotation on pp. 98–99.

37. Silverman, L. P., and Spruill, N.L. (1977). Urban crime and the price of heroin. Journal of Urban Economics, 4, 80–103.

38. Inciardi, J. A. (1995). Crack, crack house sex, and HIV risk. Archives of Sexual Behavior, 24, 249–269. McCoy, V. H.; Inciardi, J. A.; Metsch, L. R.; Pottieger, A.; and Saum, C.A. (1995). Women, crack, and crime: Gender comparisons of criminal activity among crack cocaine users. Contemporary Drug Problems, 22 (3), 435–452. Surrat, H. L.; Inciardi, J. A.; Kurtz, S. P.; and Kiley, M. C. (2004). Sex work and drug use in a subculture of vio- lence. Crime and Delinquency, 50, 43–59.

39. Barker, T., and Human, K. M. (2009). Crimes of the Big Four motorcycle gangs. Journal of Criminal Justice, 37, 174–179. Bellair, P. E., and McNulty, T. L. (2009). Gang membership, drug selling, and violence in neigh- borhood context. Justice Quarterly, 26, 644–669. Howell, J. C., and Decker, S. H. (1999, January). The youth gangs, drugs, and violence connection. OJJDP Juvenile Justice Bulletin. Washington DC: Office of Juvenile Justice and Delinquency Prevention, U.S. Department of Justice. McDermott, E. J. (2006, Winter). Motorcycle gangs: The new face of organized crime. Journal of Gang Research, 13, 27–36.

40. McDermott, Motorcycle gangs. 41. Bellair and McNulty, Gang membership. Howell, J. C.,

and Gleason, D. K. (1999, December). Youth gang drug trafficking. OJJDP Juvenile Justice Bulletin. Washington DC: Office of Juvenile Justice and Delinquency Pre- vention, U.S. Department of Justice. Decker, S.; Katz, C. M.; and Webb, V. J. (2008). Understanding the black box of gang organization: Implications for involvement in violent crime, drug sales, and violent victimization. Crime and Delinquency, 54, 153–172.

42. Office of Juvenile Justice and Delinquency Prevention (1999, July). 1996 National Youth Gang Survey. Sum- mary. Washington, DC: U.S. Department of Justice, pp. 38–39.

43. Bugliosi, V. T. (1991). Drugs in America: A citizen’s call to action. New York: Knightsbridge Publishing, p. 25.

44. Brecher. Licit and illicit drugs, pp. 6–7. 45. Office of National Drug Control Policy (2012,

February). Executive summary. National Drug Control Strategy: FY 2013 Budget Summary. Washington, DC: White House Office of National Drug Control Policy.

46. Eckholm, E. (2010, January 25). Border tribe feels stuck in middle of drug war. New York Times, A1, A10. Luhnow, D., and De Cordoba, J. (2009, December 23). Hit men kill Mexican hero’s fam- ily. Wall Street Journal, p. A1. Malkin, E. (2009, December 23). Vengeful fury in drug war chills Mexico. New York Times, pp. A1, A12. Mazzetti, M., and Thompson, G. (2011, August 28). U.S. widens role in Mexican fight. New York Times, pp. A1, A3. Rubin, A. J. (2012. January 2). In Afghanistan, poppy growing proves resilient. New York Times, pp. A1, A8.

47. Forero, J. (2006, August 19). Colombia’s coca survives U.S. plan to uproot it. New York Times, pp. A1, A8. Lacey, M. (2008, December 5). Hospitals now a theater in Mexico’s drug war. New York Times, pp. A1, A18. Moreau, R., and Yousafkai, S. (2006, January 9). A har- vest of treachery. Newsweek, pp. 32–35. National Drug Intelligence Center (2011, August). National Drug Threat Assessment 2012. Washington, DC: U.S. Depart- ment of Justice.

48. Gray, J. P. (2001). Why our drug laws have failed and what we can do about it: A judicial indictment of the war on drugs. Philadelphia: Temple University Press. Gold- stein, A. (2001). Addiction: From biology to drug policy (2nd ed.). New York: Oxford University Press, pp. 307– 328. Treaster, J. B. (1992, June 14). Twenty years of war on drugs. New York Times, p. E7.

58 ■ Part One Drugs in Society/Drugs in Our Lives

The following discussion of view- points represents the opinions of people on both sides of the con- troversial issue of the legalization of drugs. Read them with an open mind. You don’t have to come up with the final answer, nor should you necessarily agree with the ar- gument you heard last. Many of the ideas in this discussion come from the sources listed.

POINT Legalization would get the prob- lem under some degree of control. The “war on drugs” does nothing but increase the price of illicit drugs to what the market will bear, and it subsidizes the drug dealers and drug barons around the world. If we legalize drugs, we can take the profit out of the drug business because legalization would bring the price down dramatically. We could regulate drug sales, as we do now with nicotine and alcohol, by setting up centers that would be licensed to sell cocaine and heroin, as well as sterile syringes, while any drug sales to minors would remain a criminal offense. Regulations would also ensure that drugs maintained standards of purity; the health risks of drug contamination would be avoided.

COUNTERPOINT Legalization is fundamentally im- moral. How can we allow people to run to the nearest store and destroy their lives? Don’t we as a society have a responsibility for the health and welfare of people in general?

If the drugs (pure or impure) were available, the only effect would be to increase the number of drug abusers. When Brit ain allowed physicians to prescribe heroin to “registered” addicts, the number of heroin addicts rose fivefold (or more according to some informal estimates), and there were then cases of medical abuse as well as drug abuse. A few unscrupulous doctors were prescribing heroin in totally inappropriate amounts, and a new drug culture was created.

POINT How moral is the situation now? We have whole communities liv- ing at the mercy of drug dealers. Any increase in drug users would be more than compensated for by the gains of freedom from such people. Even if the sale of crack were kept illegal, conceding that this drug is highly dangerous to society, we would have an 80 per- cent reduction in the black market for drugs, a substantial gain for the welfare of society. We can’t guar- antee that our inner cities would no longer be places of hopeless- ness and despair, but at least we would not have the systemic violence associated with the drug world. Besides, with all the money saved from programs set up to pre- vent people from getting hold of illicit drugs, we could increase the funding for drug treatment pro- grams for all the drug abusers who want them and for research into ways of understanding the nature of drug dependence.

COUNTERPOINT No doubt, many drug abusers seek out treatment and want to break their drug dependence. Perhaps there may be some individuals who seek treatment under legalization because there would no longer be a social stigma associated with drug abuse, but many drug abusers have little or no long-term commitment to drug treatment. In the pres- ent situation, the illegality of their behavior enables us to compel them to seek and stay in treatment, and we can monitor their abstinence by periodic drug testing. How could we do this if using the drug were legal? Besides, how would we approach the education of young people if drugs were legal? We could not tell them that cocaine would give them cancer or emphysema, as we warn them of the dangers of nicotine, only that it would prevent them from being a productive member of society and would have long-term effects on their brains. If the adults around them were allowed to take cocaine, what would be the mes- sage to the young? Simply wait until you’re twenty-one?

POINT We already have educational pro- grams about alcohol abuse; the message for heroin and cocaine abuse would be similar. The loss of productivity due to any increased availability of drugs would not be as significant as the present loss of pro- ductivity we have with alcohol and cigarettes. With the tax revenues ob- tained from selling drugs legally, we

P A R t O N E

Drugs in Society/Drugs in Our Lives

Point/Counterpoint I

Should We Legalize Drugs in General?

Chapter 2 Drug-Taking Behavior: Personal and Social Issues ■ 59

could have money for more exten- sive anti-drug advertising. We could send a comprehensive message to our youth that, in terms of address- ing the problems in their lives, there are alternatives to psychoactive substances. In the meantime, we would be removing the “forbidden fruit” factor in drug-taking behavior. Drugs wouldn’t be a big deal.

COUNTERPOINT Arguing that people t ake drugs because they are forbidden or hard to get ignores the basic psychologi- cal allure of drugs. If you lowered the price of a very expensive sports car, would fewer people want to buy one? Of course not. People would want a fast car because they like fast cars, just as people will still want to get high on drugs. Legal- izing currently illicit drugs would only encourage the development of more dangerous drugs in the future. Look at what happened with crack. Cocaine was bad enough, but when crack appeared on the scene, the situation grew far worse.

POINT It can be argued that crack was marketed because st andard co- caine powder was too expensive for people in the inner cities. If cocaine had been legally available, crack might never have been cre- ated because the market would not have been there. Even with crack

remaining illegal under a legaliza- tion plan, there is at least the possi- bility that the appeal of crack would decline. The trend lately is that il- legal drugs are getting stronger, while legal drugs (alcoholic bev- erages and cigarettes) are getting weaker as people become more health-conscious. Legalization might make presently illicit drugs weaker in strength, as public opin- ion turns against them. The main problem we face is that spending 60 percent of a multibillion-dollar drug-law-enforcement program on the “supply” side of the question, and only 40 percent on reduc- ing the demand for drugs, is not working. If one source of drugs is controlled, another source takes its place. The link between drugs and crime is a direct result of the illegal- ity of drugs. It’s not the drug addicts who are destroying the country; it’s the drug dealers. Right now, the criminals are in charge. We have to change that. Only legaliza- tion would take away their profits and refocus our law-enforcement efforts on other crimes that con- tinue to undermine our society.

COUNTERPOINT The frustration is understandable, but let’s not jump into something merely because we’re frustrated. We can allocate more funds for treatment without making drugs legal. We can increase funds for

scientific research without mak- ing drugs legal. We need a more balanced program, not an entirely new one. Polls do not indicate general support for drug legaliza- tion. Between 60 percent and 80 percent of the U.S. public supports continued prohibition of drugs. Most citizens appear to recognize that legalization would make a bad situation worse, not better.

Critical Thinking Questions for Further Debate 1. Suppose you were a legislator

considering new regulatory laws with respect to psychoactive drugs. What would be your argu- ment in favor of making a distinc- tion between “hard drugs” such as heroin, cocaine, and metham- phetamine, and “soft drugs” such as marijuana and hallucinogens? On what basis would you make such a distinction?

2. Suppose that social regulations based on a Harm Reduction ap- proach were implemented and the consequence was that drug abuse became more prevalent. Would you revert to a Zero Tol- erance approach or reexamine the assumptions of the Harm Reduction approach and alter it to produce more positive so- cietal effects?

Point/Counterpoint II can be found on pages 116–117.

Sources: Dennis, R. J. (1990, November). The economics of legalizing drugs. The Atlantic, 126–132. Goldstein, A. (2001). Addiction: From biology to drug policy (2nd ed.). New York: Oxford University Press. Goode, E. (1997). Between politics and reason: The drug legalization debate. New York: St. Martin’s Press. Gray, J. P. (2001). Why our drug laws have failed and what we can do about it. Philadelphia: Temple University Press. Levinthal, C. F. (2003). Point/Counterpoint: Oppos- ing perspectives on issues of drug policy. Boston: Allyn and Bacon, Chapter 1. Wilson, J. Q. (1990, February). Against the legalization of drugs. Commentary, 21–28.

60

After you have completed this chapter, you should have an understanding of

▶ The ways drugs are administered and later eliminated from the body

▶ Factors determining the behavioral impact of drugs

▶ The sympathetic and parasympathetic branches of the autonomic nervous system

▶ The basic structures of the brain

▶ How neurons work, and how they communicate with each other

▶ The functions of seven major neurotransmitters in the brain

▶ How psychoactive drugs influence neuronal communication

▶ The physiological basis for tolerance effects and psychological dependence

▶ The placebo effect in drug- taking behavior

How Drugs Work in the Body and on the Mind

C h a p t e r

3

You can think of addiction as a form of “learning gone

bad.”

Drugs can infiltrate into the brain because they can

speak the brain’s own language.

Neurochemical pathways and synaptic processes

have no choice but to respond to drugs as they do to

chemicals and signals that occur naturally in the brain,

which are far gentler and have served us well for millions

of years.

Meanwhile, drugs are hijacking the brain. They

ambush, alter, corrupt, infest, curtail. They commandeer

brain processes, reshape networks. And their demands

escalate over time.

The results are not pretty. The brain is now a mess. Not

surprisingly, life is now a mess.

Reflections on substance abuse from the perspective of neuroscience1

Chapter 3 How Drugs Work in the Body and on the Mind ■ 61

You might have heard of the classic public-service announcement, which aired frequently on television in the late 1980s:

This is your brain (image of an egg held in hand). This is drugs (image of a sizzling frying pan). This is your brain on drugs (image of the egg frying in pan). Any questions?2

Giving the viewer considerable “food for thought,” this message had an immediate impact on the American public: Don’t do drugs because drugs will fry your brain. The creators of this message were speaking metaphori- cally, of course. In effect, they were saying that certain classes of drugs have a devastating impact on the human brain. Therefore, stay away from them.

It was (and still is) an important message to convey, though it can be argued that there are better ways to per- suade people not to do something than by seeing scary images. Nonetheless, those who felt the impact of watch- ing that egg fry found the experience hard to forget.

At the same time, an equally important message is that there are other classes of drugs that have enor- mously beneficial effects on the brain. Drugs are used to treat major mental illnesses such as schizophrenia and depression (see Chapter 15) and play a major role in reducing pain and relieving feelings of anxiety (see Chapters 5 and 13). Whether drugs in general have a positive or a negative effect on us depends, at least in part, on how they interact with physiological processes in the body.

As noted in Chapter 1, psychoactive drugs affect our behavior and experience through their effects on brain

functioning. Therefore, our understanding of drugs and their effects is closely connected with the progress we have made in our understanding of the ways drugs work in the brain. This chapter will describe the basic func- tions of the nervous system and the ways in which drugs alter these functions. It will serve as a foundation for understanding specific classes of drugs covered in the chapters that follow.

A reasonable place to start is to ask the question: How do drugs get into the body in the first place?

How Drugs Enter the Body

There are four principal routes through which drugs can be delivered into the body: oral administration, injection, inhalation, and absorption through the skin or membranes. In all four delivery methods, the goal is for the drug to be absorbed into the bloodstream. In the case of psychoactive drugs, a drug effect depends not only on its reaching the bloodstream but on its reaching the brain as well.

Oral Administration Ingesting a drug by mouth, digesting it, and absorbing it into the bloodstream through the gastrointestinal tract is the oldest and easiest way of taking a drug. On the one hand, oral administration and reliance on the digestive process for delivering a drug into the bloodstream pro- vides a degree of safety. Many naturally growing poisons taste so vile that we normally spit them out before swal- lowing; others will cause us to be nauseated, and the drug will be expelled through vomiting. In the case of hazardous substances that are not immediately rejected, we can benefit from the fact that the absorption process for orally administered drugs is relatively slow. Gener- ally speaking, it takes between five and thirty minutes after ingestion for most of the absorption process to be completed. Therefore, there is at least a little time after accidental overdoses or suicide attempts to induce vom- iting or pump the stomach.

On the other hand, the gastrointestinal tract con- tains a number of natural barriers that slow down or, in some cases, prevent the absorption of certain drugs that we might actually want to absorb. One such barrier is related to a drug’s alkalinity or acidity (defined as its pH value). The interior of the stomach is highly acidic, and the fate of a particular drug depends on how it reacts with that environment. Weakly acidic drugs such as aspirin are absorbed better in the stomach than highly alkaline drugs such as morphine, heroin, and cocaine. Insulin

by the numbers . . .

100 billion Estimated number of neurons in the human brain

10–100 trillion Estimated number of synapses in the human brain

20–25 Approximate wattage of a light bulb, equivalent to the total electrical power generated by the brain

Sources: Drachman, D. (2005). Do we have brain to spare? Neurology, 64, 2004–2005. Kety, S. (1961). Energy metabolism of the brain during sleep. In G. E. W. Wolstenhome and M. O’Connor (Eds.). CIBA Foundation Symposium on the nature of sleep. Boston: Little, Brown, pp. 375–381. Thompson, R. F. (1993). The brain: A neuroscience primer (2nd ed.). New York: Freeman, pp. 75, 299.

62 ■ Part One Drugs in Society/Drugs in Our Lives

is destroyed by stomach acid, so it cannot be adminis- tered orally, whereas a neutral (neither acidic nor alka- linic) substance, such as alcohol, is readily absorbed at all points along the gastrointestinal tract. In the case of alcohol, the brain gets the message very quickly.

If it survives the stomach and gets to the small intestine, the drug still needs to proceed from that point into the bloodstream. The membrane separat- ing the intestinal wall from blood capillaries is made up of two layers of fat molecules, making it necessary for substances to be lipid-soluble (soluble in fats) in order to pass through. Even after successful absorption into blood capillaries, however, substances must then pass through the liver for a “screening process” before being released into the general circulation. Enzymes in the liver are capable of breaking down (metabo- lizing) the molecular structure of certain drugs, thus reducing the amount that eventually enters the blood- stream. This function of the liver, referred to as first- pass metabolism, plays an essential role in protecting us from potentially toxic substances that might have been ingested by mouth. A further barrier, which sepa- rates the bloodstream (circulatory system) from brain tissue itself, will be discussed in a later section.

As a result of all these natural barriers, orally admin- istered drugs need to be ingested at deliberately elevated dose levels, to allow for the fact that some proportion of the drug will not make it through to the bloodstream. We can try to compensate for the loss of the drug dur- ing digestion, but we are often only making an edu- cated guess. The internal state of the gastrointestinal tract changes constantly over time, making it either more or less likely that a drug will reach the circulatory system. The presence or absence of undigested food,

whether the undigested food interacts with the chemi- cal nature of the drug, and the activity level of specific liver enzymes that control the absorption of the drug into the bloodstream are examples of factors that make it difficult to make exact predictions about the strength of the drug when it finally enters the bloodstream (see Chapter 14).

Injection One solution to the problems of oral administration is to bypass the digestive process entirely and deliver the drug more directly into the bloodstream through a hypoder- mic syringe and needle.

A very fast means of injection is an intravenous (i.v.) injection, as the drug is delivered into a vein with- out any intermediary tissue. An intravenous injection of heroin in the forearm, for example, arrives at the brain in less than fifteen seconds. The effects of abused drugs delivered in this way, often called mainlining, are not only rapid but also extremely intense. In a medical setting, intravenous injections provide a great deal of control over dosage and the opportunity to administer multiple drugs at the same time. The principal disad- vantage, however, is that the effects of intravenous drugs are irreversible. In the event of a mistake or unexpected reaction, there is no turning back unless some other drug (called an antidote) is available that can counteract the first one. In addition, repeated injections through a particular vein may cause the vein to collapse or develop a blood clot.

With intramuscular (i.m.) injections, the drug is delivered into a large muscle (usually in the upper arm, thigh, or buttock) and is absorbed into the bloodstream through the capillaries serving the muscle. Intramuscu- lar injections have slower absorption times than intra- venous injections, but they can be administered more rapidly in emergency situations. Our exposure to intra- muscular injections comes early in our lives when we receive the standard schedule of inoculations against diseases such as measles, diphtheria, and typhoid fever. Tetanus and flu shots are also administered in this way.

A third injection technique is subcutaneous (s.c. or sub-Q) delivery, in which a needle is inserted into the tissue just underneath the skin. Because skin has a less abundant blood supply relative to muscle, a subcu- taneous injection has the slowest absorption time of all

intravenous (i.v.): Into a vein.

intramuscular (i.m.): Into a muscle.

subcutaneous (s.c. or sub-Q): Underneath the skin.

Alcohol is easily absorbed into the bloodstream and the brain. For other orally consumed drugs, however, absorption is relatively slow, because they must first be processed by the digestive system.

Chapter 3 How Drugs Work in the Body and on the Mind ■ 63

the injection techniques. It is best suited for situations in which it is desirable to have a precise control over the dosage and a steady absorption into the bloodstream. The skin, however, may be easily irritated by this proce- dure. As a result, only relatively small amounts of a drug can be injected under the skin, compared to the quan- tity that can be injected into a muscle or vein. When involved in drug abuse, subcutaneous injections are often referred to as skin-popping.

All injections require a needle to pierce the skin, so there is an inherent risk of bacterial or viral infec- tion if the needle is not sterile. The practice of inject- ing heroin or cocaine with shared needles, for example, promotes the spread of infectious hepatitis and HIV (see Chapter 2). When administered orally, drugs do not have to be any more sterile than the foods we eat or the water we drink.

Inhalation Next to ingesting a drug by mouth, the simplest way of receiving its effects is to inhale it in some form of gas- eous or vaporous state. The alveoli within the lungs can be imagined as a huge surface area with blood vessels lying immediately behind it. Our bodies are so depen- dent on the oxygen in the air we breathe that we have evolved an extremely efficient system for getting oxygen to its destinations. As a consequence of this highly devel- oped system, the psychoactive effect of an inhaled drug is even faster than a drug delivered through intravenous injection. Traveling from the lungs to the brain takes only five to eight seconds.

One way of delivering a drug through inhalation is to burn it and breathe in the smoke-borne particles in the air. Drugs administered through smoking include nicotine from cigarettes, opium, tetrahydrocannabinol (THC) from marijuana, free-base cocaine, crack cocaine, and crystallized forms of methamphetamine. Drugs such as paint thinners, gasoline, and glues can also be inhaled because they evaporate easily and the vapors travel freely through the air. In medical settings, surgical anesthetics are administered through inhalation because the concen- tration of the drug can be precisely controlled.

The principal disadvantage of inhaling smoked drugs, as you probably expect, arises from the long-term hazards of breathing particles in the air that contain not only the active drug but also tars and other substances produced by the burning process. In general, emphy- sema, asthma, and lung cancer can result from smok- ing (see Chapter 10). It is also possible, in any form of drug inhalation, that the linings leading from the throat to the lungs will be severely irritated over time.

Absorption through the Skin or Membranes Drug users over the ages have been quite creative in finding other routes through which drugs can be admin- istered. One way is to sniff or snort a drug in dust or pow- der form into the nose. Once inside the nose, it adheres to thin mucous membranes and dissolves through the membranes into the bloodstream. This technique, referred to as an intranasal administration, is commonly used in taking snuff tobacco or cocaine. Prescription medications are becoming increasingly available in

Drugs administered by smoking and consumed by inhalation are absorbed extremely quickly, aided by a very efficient deliv- ery system from the alveoli in the lungs to the bloodstream and from the bloodstream to the brain. Two men engaged in smoking crack cocaine are depicted here.

intranasal: Applied to the mucous membranes of the nose.

64 ■ Part One Drugs in Society/Drugs in Our Lives

nasal-spray formulations, avoiding the need for needle injections or difficult-to-swallow pills.

Snuff tobacco, chewing tobacco, and cocaine- containing coca leaves can also be chewed without swallowing over a period of time or simply placed in the inner surface of the cheek and slowly absorbed through the membranes of the mouth. Nicotine chewing gums, available for those individuals who wish to quit tobacco smoking, work in a similar way. Nitroglycerin tablets for heart disease patients are typically administered sublin- gually, with the drug placed underneath the tongue and absorbed into the bloodstream.

At the opposite end of the body, medicines can be inserted as a suppository into the rectum, where the sup- pository gradually melts and the medicine is absorbed through thin rectal membranes into the bloodstream. This method is less reliable than oral administration, but it may be necessary if the individual is vomiting or unconscious at the time.

Another absorption technique involves a trans- dermal patch, which allows a drug to slowly diffuse through the skin. Transdermal patches have been used for long-term administration of nitroglycerin, estrogen, nicotine, and medications for motion sickness, Parkin- son’s disease, and Alzheimer’s disease. Newly developed procedures to enhance the process of skin penetration include the promising technique of administering low- frequency ultrasound, which allows large molecules, such as those of insulin, to pass through the skin. Insulin administration is an especially interesting application because, until now, the only effective way of getting it into the bloodstream has been through needle injection.

Alternative methods under development include small silicon chip patches containing a grid of microscopic needles that painlessly pierce the skin and allow the passage of large molecules into the bloodstream. Other techniques involve a mild electric current that propels the medication through the skin or the application of medication with

special compounds that help the medication slip through skin pores. Advantages in nanotechnology have made it possible to provide “smart patches” that can be pro- grammed to schedule specific doses of transdermal medi- cation that match the fluctuating needs of the patient.3

Drugs . . . in Focus summarizes the various ways in which drugs can be administered into the body.

How Drugs Exit the Body

Having reviewed how a drug is absorbed into the blood- stream and, in the case of a psychoactive drug, into the brain, we can now consider the ways in which the body eliminates it. The most common means of elimina- tion is through excretion in the urine after a series of actions in the liver and kidneys. Elimination also occurs through excretion in exhaled breath, feces, sweat, saliva, or (in the case of nursing mothers) breast milk.

The sequence of metabolic events leading to uri- nary excretion begins with a process called biotransfor- mation, chiefly through the action of specific enzymes in the liver. The products of biotransformation, referred to as metabolites, are structurally modified forms of the original drug. Generally speaking, if these metabolites are water-soluble, they are passed along to the kidneys and eventually excreted in the urine. If they are less water-soluble, then they are reabsorbed into the intes- tines and excreted through defecation. On rare occa- sions, a drug may pass through the liver without any biotransformation at all and be excreted intact. The hallucinogenic drug Amanita muscaria is an example of this kind of drug (see Chapter 6).

A number of factors influence the process of bio- transformation and urinary excretion and, in turn, the rate of elimination from the body. For most drugs, bio- transformation rates will increase as a function of the drug’s concentration in the bloodstream. In effect, the larger the quantity of a drug, the faster the body “tries” to get rid of it. An exception, however, is alcohol, for which the rate of biotransformation is constant, no matter how much alcohol has been ingested (see Chapter 8).

The activity of enzymes required for biotransfor- mation may be increased or decreased by the presence

sublingual: Applied under the tongue.

transdermal patch: A device attached to the skin that slowly delivers the drug through skin absorption.

biotransformation: The process of changing the molecular structure of a drug into forms that make it easier for the body to excrete it.

metabolite (me-TAB-oh-lite): A by-product resulting from the biotransformation process.

This skin patch contains a rectangular array of 50 micro- needles, each 620 microns in length and thinner than a human hair. Tiny, painless epidermal punctures are created by pressing the needles against the skin. Each puncture acts as a conduit for medication to flow evenly from the skin patch into dermal capillaries and the bloodstream.

Chapter 3 How Drugs Work in the Body and on the Mind ■ 65

Drugs . . . in Focus

Ways to Take Drugs: Routes of Administration Oral Administration (by Mouth) • Method: By swallowing or consuming in eating or

drinking • Advantages: Slow absorption time; possibility of reject-

ing poisons and overdoses • Disadvantages: Slow absorption time; no immediate

effect • Examples: Medications in pill form, marijuana

(baked in food), amphetamine and methamphetamine, barbiturates, LSD (swallowed or licked off paper), PCP, opium, methadone, codeine, caffeine, alcohol

Injection (by Hypodermic Syringe)

Intravenous Injection • Method: By needle positioned into a vein • Advantages: Very fast absorption time; immediate

effects • Disadvantages: Cannot be undone; risks of allergic

reactions • Examples: PCP, methamphetamine, heroin,

methadone, morphine

Intramuscular Injection • Method: By needle positioned into a large muscle • Advantages: Quicker to administer than an intravenous

injection • Disadvantages: Somewhat slower absorption time than

an intravenous injection; risk of piercing a vein by accident

• Examples: Vaccine inoculations

Subcutaneous Injection • Method: By needle positioned underneath the skin • Advantages: Easiest administration of all injection

techniques

• Disadvantages: Slower absorption time than an intramuscular injection; risk of skin irritation and deterioration

• Examples: Heroin and other narcotics

Inhalation (by Breathing)

Smoking • Method: By burning drug and breathing smoke-borne

particles into the lungs • Advantages: Extremely fast absorption time • Disadvantages: Effect limited to time during which

drug is being inhaled; risk of emphysema, asthma, and lung cancer from inhaling tars and hydrocarbons in the smoke; lung and throat irritation over chronic use

• Examples: Nicotine (from tobacco), marijuana, hashish, methamphetamine, ice or crystal metham- phetamine, free-base cocaine, crack cocaine, PCP, heroin, and opium

Vaporous Inhalation • Method: By breathing in vapors from drug • Advantages: Extremely fast absorption time • Disadvantages: Effect limited to time during which

drug is being inhaled; lung and throat irritation over chronic use

• Examples: Surgical and dental anesthetics, paint thinners, gasoline, cleaning fluid

Absorption (through Skin or Membranes) • Method: By positioning drug against skin, inserting it

against rectal membrane, snorting it against mucous membranes of the nose, or placing it under the tongue or against the cheek so it diffuses across into bloodstream

• Advantages: Quick absorption time • Disadvantages: Irritation of skin or membranes • Examples: Cocaine, amphetamine, methamphetamine,

nicotine patches and gums, naltrexone (an opioid antagonist, see Chapter 5), snuff tobacco, coca leaves

66 ■ Part One Drugs in Society/Drugs in Our Lives

of other drugs in the body. As a result, the physiological effect of one drug may interact with the effect of another, creating a potentially dangerous combination. An indi- vidual’s age can also be a factor. Because enzyme activ- ity levels in the liver decline after the age of forty, older people eliminate drugs more slowly than younger people. We will look at the consequences of drug interactions and individual differences in the next section of this chapter.

Finally, it is important to point out that drugs are gradually eliminated from the body at different rates simply on the basis of their chemical properties. In gen- eral, fat-soluble drugs are eliminated more slowly than water-soluble drugs. The index of how rapidly or slowly a particular drug is eliminated is referred to as its elimi- nation half-life, defined as the amount of time it takes for the drug in the bloodstream to decline to 50 percent of its original concentration level. As an example, sup- pose the elimination half-life of Drug X is one hour. After one hour, the drug concentration would be one- half of the original; after two hours, it would be one- fourth of the original. After five hours, the concentration would be about three percent (1/32th) of the original.

Many drugs, such as cocaine and nicotine, have elimination half-lives of only a few hours; marijuana and some prescription medications are examples of drugs with much longer half-lives.4 Understanding the variation in the elimination rates of drugs and their metabolites is extremely important in the development of drug-testing procedures to detect drug-taking behav- ior, a topic to be examined in Chapter 12.

Factors Determining the Behavioral Impact of Drugs

If a drug is administered repeatedly, the timing of the administrations plays an important role in determining the final result. When two drugs are administered close together in time, we must also consider how these drugs might interact with each other in terms of their acute effects. The chronic effects of two drugs might interact as well. Finally, it is possible that the same drug at the same dosage taken by two individuals might have different effects by virtue of some inherent characteristic (such as body weight, gender, ethnicity) of the drug user.

Timing All drugs, no matter how they are delivered, share some common characteristics when we consider their effects over time. There is initially an interval (the latency period) during which the concentration of the drug is increasing in the bloodstream but is not yet high enough for the behavioral effect of the drug to be detected. How long this latency period lasts is related generally to the absorption time of the drug. As the concentration of the drug continues to rise, the effect becomes stronger. A stage is eventually reached when the effect attains a maximum strength, even though the concentration in the blood continues to rise. This point is unfortunately the point at which the drug may produce undesirable side effects. One solution to this problem is to administer the drug in a time-release form (designated as controlled- release, extended-release, or sustained-release formula- tions). In this approach, a large dose is given initially to enable the drug effect to be felt; then smaller doses are programmed to be released at specific intervals afterward to postpone, up to twelve hours or so, the decline in the drug’s concentration in the blood. The intention is to keep the concentration of the drug in the blood within a “therapeutic window”—high enough for the drug to be effective but low enough to avoid any toxic effects. When drugs are administered repeatedly, there is a risk that the second dose will boost the concentration of the drug in the blood too high before the effect of the first dose has had a chance to decline (Figure 3.1).

0

0

1

2 4 6

B lo

o d

le ve

l

Hours

Therapeutic threshold

Toxic threshold

Therapeutic window

F I g u r e 3 . 1

The therapeutic window. Time-release drugs are formulated to administer the drug in small amounts over time to stay above the threshold for a therapeutic effect but below the threshold for toxicity.

elimination half-life: The length of time it takes for a drug to be reduced to 50 percent of its equilibrium level in the bloodstream.

latency period: An interval of time during which the blood levels of a drug are not yet sufficient for a drug effect to be observed.

Chapter 3 How Drugs Work in the Body and on the Mind ■ 67

Drug Interactions Two basic types of interactions may occur when two drugs are mixed together. In the first type, two drugs in combination may produce an acute effect that is greater than the effect of either drug administered separately. In some cases, the combination effect is merely additive. For example, if the effect of one drug alone is equiva- lent to a 4, and the effect of another drug is a 6, then the combined additive effect is equivalent to a value of 10.

In other cases, however, the acute combination effect is hyperadditive, with the combined effect exceed- ing the sum of the individual drugs administered alone, as in the two drugs in the first example combining to a value of 13 or more. Any hyperadditive effect produced by a combination of two or more drugs is referred to as synergism. In some synergistic combinations, one drug may even double or triple the effect of another. It is also possible that one drug might have no effect at all unless it is taken simultaneously with another. This special form of synergism is called potentiation; it is as though a drug with no effect at all by itself, when combined with a drug having an effect of 6, produces a result equivalent to a 10. The danger of such interactions is that the combined effect of the drugs is so powerful as to become toxic. In extreme cases, this toxicity can be lethal.

In the second type of interaction, two drugs can be antagonistic if the acute effect of one drug is diminished to some degree when administered with another—a sit- uation comparable to a drug with the effect of 6 and a drug with the effect of 4 combining to produce an effect of 3. Later chapters discuss drugs that are totally antago- nistic to each other, in that the second exactly cancels out, or neutralizes, the effect of the first. Health Alert (page 68) warns that dangerous interactions can result not only from drug–drug combinations but from food– drug combinations as well.

Cross-Tolerance and Cross-Dependence If you were taking a barbiturate (a sedation-producing drug that acts to depress bodily functioning) for an extended length of time, and you developed a tolerance for its effect, you might also have developed a tolerance for another depressant drug, even though you had never taken the second one. In other words, it is possible for a tolerance effect for one drug to automatically induce a tolerance for another. This phenomenon, referred to as cross-tolerance, is commonly observed in the physiolog- ical and psychological effects of alcohol, barbiturates, and a class of antianxiety medications called benzodi- azepines (Chapter 13). As a result of cross-tolerance, an

alcoholic will have already developed a tolerance for a barbiturate, or a barbiturate abuser will need a greater amount of an anesthetic when undergoing surgery.

We can view the interconnectedness of depressant drugs in another way as well. If withdrawal symptoms of one drug are relieved by administering another drug, then the two drugs show cross-dependence. In effect, one drug can substitute for whatever physiological

Quick Concept Check 3.1

Understanding Drug Interactions Check your understanding of drug interactions by assuming the following values represent the effects of Drugs A, B, and C, when taken individually:

• Drug A 0 • Drug B 20 • Drug C 35

Identify the type of drug interaction when the following values represent the effect of two drugs in combination.

1. Drug A combined with Drug B 30

2. Drug B combined with Drug C 55

3. Drug A combined with Drug C 15

4. Drug B combined with Drug C 85

5. Drug B combined with Drug C 0

6. Drug A combined with Drug B 20

Answers: 1. potentiation 2. additive 3. antagonistic 4. synergistic (hyperadditive) 5. antagonistic 6. additive

synergism (SIN-er-jih-zum): The property of a drug interaction in which the combination effect of two drugs exceeds the effect of either drug administered alone.

potentiation: The property of a synergistic drug inter- action in which one drug combined with another drug produces an enhanced effect when one of the drugs alone would have had no effect.

cross-tolerance: A phenomenon in which the toler- ance that results from the chronic use of one drug induces a tolerance effect with regard to a second drug that has not been used before.

cross-dependence: A phenomenon in which one drug can be used to reduce the withdrawal symp- toms following the discontinuance of another drug.

68 ■ Part One Drugs in Society/Drugs in Our Lives

H e A l T H A l e r T !

Adverse effects of Drug–Drug and Food–Drug Combinations It would be impossible to list every known drug–drug interaction or food–drug interaction. Nonetheless, here are some examples. Any adverse reaction to a combination of drugs or a combination of a drug with something eaten should be reported to your physician immediately. An awareness of adverse interactions is particularly important for elderly patients, who tend to be treated with multiple medications. The best advice is to ask your physician whether alcohol, specific foods, or other medications might alter the effect of your medication.

Hyperadditive Effects Alcohol with barbiturate-related sleep medications, cardiovascular medications, insulin, anti-inflammatory medications, antihistamines, painkillers, antianxiety medications Septra, Bactrim, or related types of antibiotics with Coumadin (an anticoagulant) Tagamet (a heartburn and ulcer treatment medication) with Coumadin Aspirin, Aleve, Advil, Tylenol, or related painkillers with Coumadin Plendil (a blood pressure medication) and Procardia (an angina treatment), as well as Zocor, Lipitor, and Mevacor (all cholesterol-lowering medications), with grapefruit juice Lanoxin (a medication for heart problems) with licorice Lanoxin with bran, oatmeal, or other high-fiber foods

Antagonistic Effects Morphine/heroin with naloxone or naltrexone Norpramin or related antidepressants with bran, oatmeal, or other high-fiber foods Soy products and certain vitamin K–rich vegetables (such as broccoli, cabbage, and asparagus) with Coumadin

Possible Toxic Reactions Internal bleeding by a combination of Parnate and Anafranil (two types of antidepressants) Elevated body temperature by a combination of Nardil (an antidepressant) and Demerol (a painkiller) Excessive blood pressure or stroke by a combination of Parnate, Nardil, or other monoamine-oxidase inhibitors (MAOIs) used to treat depression with cheddar cheese, pickled herring, or other foods high in tyramine Agitation or elevated body temperature by a combina- tion of Paxil, Prozac, Zoloft, or related antidepressants with Parnate, Nardil, or other monoamine-oxidase inhibitors (MAOIs) used to treat depression Irregular heartbeat, cardiac arrest, and sudden death by a combination of Hismanal or Seldane (two antihis- tamines) with Nizoral (an antifungal drug)

Note: The hyperadditive effects of grapefruit on certain medications can be dangerous or useful, depending on the circumstances. If grapefruit enhances the effect of the cholesterol-reducing medication Lipitor, for example, it is possible that drinking grapefruit juice might allow the pa- tient to take less Lipitor (reducing costs and possible side effects) and still receive the same level of benefit. Combi- nations of this kind, however, should be administered only under the close supervision of one’s physician.

Sources: Graedon, J., and Graedon, T. (2000, October 16). Say “aaah”: The people’s pharmacy; drugs and foods can interact adversely. Los Angeles Times, p. 2. Graedon, J., and Graedon, T. (1997). Deadly drug interactions. New York: St. Martin’s Press. PDR: Guide to drug interactions, side effects, and indications (2007). Montvale, NJ: PDR Network. Sorensen, J. M. (2002). Herb–drug, food–drug, nutrient–drug, and drug–drug interactions: Mechanisms involved and their medical implications. Journal of Alternative and Complementary Medicine, 8, 293–308.

Where to go for assistance: www.drugs.com/drug-interactions.php

Register free and check out any combination of prescription or OTC drugs for potential adverse interactions.

effects have been produced by a second drug that has been discontinued. Unfortunately, cross-dependence provides a means for continuing an abused drug in the guise of a new one. If someone wanted to conceal a pat- tern of drinking from the family, for example, a dose of

diazepam (Valium), an antianxiety medication, might suffice as a substitute for that “morning eye opener.”5

Later in this chapter, we will examine the physi- ological mechanism that underlies the phenomena of cross-tolerance and cross-dependence.

Chapter 3 How Drugs Work in the Body and on the Mind ■ 69

Individual Differences

Some variations in drug effects may be related to an interaction between the drug itself and specific charac- teristics of the person taking the drug. One characteris- tic is an individual’s weight. In general, a heavier person will require a greater amount of a drug than a lighter person to obtain an equivalent drug effect, all other things being equal. It is for this reason that drug dos- ages are expressed as a ratio of drug amount to a person’s body weight. This ratio is typically expressed in metric terms, such as milligrams-per-kilogram (mg/kg).

Another characteristic is gender. Even if a man and a woman are exactly the same weight, differences in drug effects can still result on the basis of gender differ- ences in body composition and sex hormones. Women have, on average, a higher proportion of fat, due to a greater fat-to-muscle ratio, and a lower proportion of water than men. When we look at the effects of alcohol consumption in terms of gender, we find that the lower water content (a factor that tends to dilute the alcohol in the body) in women makes them feel more intoxi- cated than men, even when the same amount of alcohol is consumed.

Relative to men, women also have reduced levels of enzymes that break down alcohol in the liver, resulting in higher alcohol levels in the blood and a higher level of intoxication.6 We suspect that the lower level of alco- hol biotransformation may be related to an increased level of estrogen and progesterone in women. Whether gender differences exist with regard to drugs other than alcohol is presently unknown.

Still another individual characteristic that influences the ways certain drugs affect the body is ethnic back- ground. About 50 percent of all people of Asian descent, for example, show low levels of one of the enzymes that normally breaks down alcohol in the liver shortly before it is excreted. With this particular deficiency, alcohol metabolites tend to build up in the blood, producing a faster heart rate, facial flushing, and nausea.7 As a result, many Asians find drinking quite unpleasant.

Ethnic variability can be seen in terms of other drug effects as well. It has been found that Caucasians have a faster rate of biotransformation of antipsychotic and antianxiety medications than Asians and, as a result, end up with relatively lower concentrations of drugs in the blood. One consequence of this difference is in the area of psychiatric treatment. Asian schizophrenic patients require significantly lower doses of antipsy- chotic medication for their symptoms to improve, and they experience medication side effects at much lower doses than do Caucasian patients. Since other possible

factors (such as diet, lifestyle, and environment) do not account for these differences, we can speculate that these differences have a genetic basis.8

In some cases, differences in the physiological response to a particular drug can explain differential patterns of drug-taking behavior. For example, research- ers have recently found that African Americans have a slower rate of nicotine metabolism following the smok- ing of cigarettes, relative to whites. This finding might be the reason why African Americans, on average, report smoking fewer cigarettes per day than whites. If we assume that an equivalent level of nicotine needs to be maintained in both populations, fewer cigarettes smoked but a higher level of nicotine absorbed per ciga- rette will produce the same effect as a greater number of cigarettes smoked but a lower nicotine level absorbed per cigarette. Consequently, African American smokers may be taking in and retaining relatively more nicotine per cigarette, and as a result not having to smoke as many cigarettes per day.9 Concerns about the specific dangers of nicotine intake among African Americans will be examined further in Chapter 10.

Introducing the Nervous System

Before we can begin to deal with the specific impact of drugs on the brain, we need first to understand some basic facts about the overall organization of the nervous system, of which the brain is a part.

In simplest terms, the nervous system is designed to do two basic things: take in information from the envi- ronment around us and control our bodily responses so that we can live effectively in that environment. But, of course, we do a lot more than that. We interpret the information coming in, try to make sense of it, remem- ber some of it for a later time, and more than occasion- ally generate some information on our own in a process called thinking.

We can understand these different functions in terms of divisions within the nervous system. In gen- eral, the nervous system is divided into the central nervous system (CNS), consisting of the brain and the spinal cord, and the peripheral nervous system,

central nervous system (CNS): The portion of the nervous system that consists of the spinal cord and the brain.

peripheral nervous system: The portion of the ner- vous system that consists of nerves and nerve fibers that carry information to the central nervous system and outward to muscles and glands.

70 ■ Part One Drugs in Society/Drugs in Our Lives

consisting of all the nerves and nerve fibers that con- nect the CNS to the environment and to our muscles and glands (Figure 3.2).

The Peripheral Nervous System The peripheral nervous system is essentially the system that brings information in and, after processing in the CNS, executes our behavioral response to that informa- tion. On the input side, it includes the visual pathway, the auditory pathway, and other channels of sensory information about the world around us. On the output side, motor pathways in the peripheral nervous system that control our reactions to that world generate two basic types of responses.

The first type, called a somatic response, is a vol- untary reaction executed by skeletal muscles that are attached to bone. When you lift your arm, for example, you have executed a series of motor commands that ultimately results in contractions of flexor and extensor muscles. In this case, the movement is deliberate, con- scious, and controlled.

A second type of reaction, called an autonomic response, is usually involuntary and executed by smooth muscles that form the walls of arteries, veins, capillaries, and internal organs, as well as cardiac muscles that form the walls of the heart. When you blush, for example, the capillaries are dilating, or enlarging, underneath the

surface of your skin, an effect that produces a red- dening color and a feeling of warmth. As some of us know from personal experience, blushing often occurs when we do not want it to, and it is dif- ficult to make it go away. And yet it is a reaction to a situation that has been processed through our sensory pathways and interpreted within the brain; in this case, some emotional content has triggered this autonomic response.

If we were to take the time to execute delib- erate commands to breathe regularly, to have our hearts beat at an appropriate rate, or to carry out the thousands of changes that our internal organs make, we would not last very long. The autonomic control that has evolved is a product of the interplay of two subsystems, each delivered to smooth and cardiac muscles and to glands through its own set of nerve fibers. These sub- systems are referred to as the sympathetic and parasympathetic branches of the autonomic nervous system.

Sympathetic and Parasympathetic Responses Autonomic responses are divided into two general cat- egories (Figure 3.3). The first is oriented toward deal- ing with some kind of emergency or stress. If we are in a situation that is perceived as a threat to our internal well-being or to our survival, the sympathetic system is in charge. During times of sympathetic activation, the heart rate goes up, blood pressure goes up, the bronchi in the lungs dilate to accommodate a greater amount of oxygen, the pupil dilates to allow more light into the eye, and other bodily systems alter their level of functioning, so we are in a better position to fight, to flee, or simply to feel frightened. At the same time, the gastrointestinal tract is inhibited. It makes sense that we should not be digesting our lunch when we are battling for our lives.

The second category of response is totally oppo- site to the first. We cannot be “on alert” all our lives; we need some time to regroup our forces, to orient ourselves toward a state of calm and rest necessary for

Nervous System

Peripheral Nervous System

Spinal and cranial nerves

Somatic System

Connects central nervous system to voluntary muscles

Autonomic System

Connects central nervous system to involuntary muscles, glands

Sympathetic System

Readies body for activity, use of energy

Parasympathetic System

Readies body for restoration of energy

Central Nervous System

Brain and spinal cord

F I g u r e 3 . 2

An “organizational chart” of the nervous system.

sympathetic branch of the autonomic nervous system: The portion of the autonomic nervous system that controls bodily changes that deal with stressful or emergency situations.

parasympathetic branch of the autonomic ner- vous system: The portion of the autonomic nervous system that controls the bodily changes that lead to increased nurturance, rest, and maintenance.

Chapter 3 How Drugs Work in the Body and on the Mind ■ 71

nurturance and internal maintenance. Heart rate and blood pressure now go down, bronchi and pupils con- strict, and the gastrointestinal tract is now excited rather than inhibited. These and other changes constitute parasympathetic activation and are an important coun- terpoint to the activation of the sympathetic system.

Some psychoactive drugs produce autonomic changes, in addition to their direct effects on the brain. They may produce a swing toward sympathetic activa- tion (as with stimulants) or a swing toward parasympa- thetic activation (as with depressants).

The Central Nervous System The central nervous system, located along the cen- tral axis of the body, consists of the spinal cord and

the brain. It is here that interpretations of our sensory input occur, and the intricate processing of informa- tion is accomplished. Some of our sensory nerves, such as those originating at locations from the neck down, enter the CNS at the level of the spinal cord; others, such as those nerves coming from our eyes and ears, enter at the level of the brain. Complex information entering at the spinal cord is carried by neural pathways upward into the brain for further processing; the processing of simpler information may not involve the brain at all, resulting instead in merely reflexive responses.

The most important part of the CNS, of course, is the brain. It is nearly impossible to overestimate its role in our everyday lives. Every gesture we make, every feeling, every experience we have of our surroundings,

Dilates

Inhibits

Relaxes (breathing more rapid)

Accelerates

Inhibits digestion

Inhibits digestion

Releases glucose

Relaxes

Inhibits

Sympathetic Parasympathetic

Constricts

Stimulates

Constricts (breathing less rapid)

Stimulates digestion

Stimulates

Stimulates

Stimulates digestion

Slows

Sex organ

Bladder

Gallbladder

Liver

Digestive tract

Pacemaker

Lung

Bronchi

Salivary gland

Pupil of eye

Contracts

Heart

F I g u r e 3 . 3

Functions of the sympathetic and parasympathetic branches of the autonomic nervous system.

Source: Baron, R. A. (2008). Psychology: From science to practice. Englewood Cliffs, NJ: Prentice Hall, p. 73. Reproduced by permission of Pearson Education, Inc.

72 ■ Part One Drugs in Society/Drugs in Our Lives

every insight or memory, is a result of a complex, beauti- fully modulated pattern of activity among approximately 100 billion specialized cells called neurons. We owe our entire cognitive universe—all of what we are or think we are—to the functioning of these cells. It is here that psychoactive drugs do their work, for good or for bad.

Understanding the Brain

Proceeding upward from the spinal cord, starting at the point where the CNS enlarges into the brain, neuro- anatomists have classified brain tissue into three major sections: the hindbrain, the midbrain, and the forebrain (Figure 3.4). The older and more primitive systems of the brain tend to be underneath the newer and more sophisticated ones, so as we travel upward from hind- brain to midbrain to forebrain on our quick tour, we are dealing with structures that have evolved ever more recently and have greater involvement in complex behaviors. You can think of this arrangement in brain anatomy as similar to an archaeological dig, where the strata of previous civilizations extend downward into greater and greater antiquity. Understanding the brain

F I g u r e 3 . 4

Basic structures of the human brain, viewed from the side.

Source: Modified from Kalat, J. W. (2007). Biological psy- chology (9th ed.). Belmont, CA: Wadsworth/ Thomson Learning. Repro- duced by permission. www. cengage.com/permissions.

Cerebellum

Midbrain

Thalamus

Cerebral cortex

Corpus callosum

Nucleus accumbens

Hypothalamus

Pituitary gland

Pons

Medulla

Spinal cord

neuron: The specialized cell in the nervous system designed to receive and transmit information.

During emergency situations, specific bodily changes are produced through stimulation of the sympathetic branch of the autonomic nervous system. First responders often function under prolonged sympathetic activation.

Chapter 3 How Drugs Work in the Body and on the Mind ■ 73

in terms of the orderliness of its development over the span of evolutionary history helps to make sense of its complexity.

The Hindbrain At the top of the spinal cord, neural tissue suddenly widens and enlarges into the hindbrain. The medulla lies at the point of the hindbrain where this enlarge- ment has just begun. It is essentially the coordinator of the basic life-support systems in our body. Blood pres- sure is controlled here, as are the rhythms of breathing, heart rate, digestion, and even vomiting. Death would be seconds away, were it not for the normal functioning of the medulla. Unfortunately, it is highly sensitive to opioids (Chapter 5), alcohol (Chapter 8), barbiturates, and other depressants (Chapter 13). When levels of any of these drugs are excessive in overdose cases, the respi- ratory controls in the medulla are inhibited, and death can result from asphyxiation (lack of breathing). Even if a person survives, the lack of oxygen in the blood while he or she is not breathing can result in severe brain damage. On a more positive note, the vomiting center in the medulla is sensitive to the presence of poisons in the blood and is able to initiate vomiting to get rid of unwanted and potentially harmful substances.

Another hindbrain structure, situated just above the medulla, is the pons. We can view the pons in terms of our ability to maintain the necessary level of alertness to survive. Within the pons are structures that determine when we sleep and when we wake up, as well as the main portion of a structure called the reticular formation that energizes the rest of the brain to be alert to incom- ing information. Drugs affecting the patterns of our sleep influence centers in the pons and reticular formation.

Behind the medulla and the pons in the hindbrain is the cerebellum, an important structure for the mainte- nance of balance and for the execution of smooth move- ments of the body. The dizziness and lack of coordination we experience after consuming alcohol are attributable in large part to alcohol’s depressive effect on the cerebellum.

The Midbrain The midbrain, located just above the hindbrain, is a center for the control of important sensory and motor reflexes, as well as for the processing of pain information.

Without a specific region of the midbrain called the substantia nigra, we would not be able to control the movements of our bodies effectively. The muscular trem- ors and other motor difficulties characteristic of Parkin- son’s disease is a result of degeneration of the substantia

nigra. Unfortunately, symptoms that resemble Parkinson’s disease have been frequently observed in patients taking antipsychotic medications for the treatment of schizophre- nia. Efforts to develop antipsychotic medications without this adverse side effect will be explored in Chapter 15.

The Forebrain Finally, in the uppermost section of the brain, are the most recently evolved systems in the brain, collectively referred to as the forebrain. One of these forebrain sys- tems, lying immediately above the midbrain, includes the hypothalamus and the limbic system. It is through these structures that we are able to carry out the moti- vational and emotional acts that ensure our survival as a species. Feeding behavior, drinking behavior, and sex- ual behavior are controlled by the hypothalamus.

The limbic system surrounds the hypothalamus and plays a central role in organizing emotional behav- ior during times of stress. Experimental lesions in points within the limbic system can turn a tame animal into a raging monster or a wild animal into a docile one. Not surprisingly, theories about the basis for psychological dependence have focused on the limbic system. Some of these ideas will be explored later in the chapter. Drugs that deal with symptoms of anxiety, depression, and schizophrenia affect regions within the limbic system.

The second forebrain system, and the most impor- tant from the standpoint of understanding human behav- ior, is a two-sided, wrinkled sheet of neural tissue, with a thickness approximately equivalent to the height of a capital letter on this page. Overhanging nearly all of the brain, the hemispheres of the cerebral cortex resemble a giant walnut, an association that prompted early physi- cians in the Middle Ages to prescribe walnuts as medi- cine for diseases of the brain (obviously a nutty idea).

When we arrive at the cerebral cortex (or cortex, for short), we have arrived at the pinnacle of the brain both functionally and spatially. Specific regions of the cerebral cortex are concerned with processing visual, auditory, and somatosensory (touch) information, while other regions control the organization of complex and precise movements.

A large percentage of cortical tissue is devoted to the task of associating one piece of information with another. In the human brain, more than 80 percent of the cortex, called the association cortex, concerns itself with the inte- gration of information. Of all the areas within the associ- ation cortex, the most recently evolved is a region closest

cerebral cortex: The portion of the forebrain devoted to a high level of information processing.

74 ■ Part One Drugs in Society/Drugs in Our Lives

to the front of the brain called the prefrontal cortex. Our higher-order, intellectual abilities (often referred to as executive functioning), as well as our personality charac- teristics, emerge from activity in this region. It has been speculated that a dysfunction in the prefrontal cortex may be associated with a loss of personal control with respect to the abuse of alcohol and other drugs.10

Understanding the Neurochemistry of Psychoactive Drugs

Gaining some perspective about brain anatomy lays the foundation for an understanding of where certain psycho- active drugs are active, but it does not help us to under- stand how they work. To answer this second question, we need to know something about neurons themselves, the specialized cells designed to communicate information

within the nervous system. As we will see, our understand- ing of neuronal communication has been critical for the insights we have gained into the nature of drug abuse.

Introducing Neurons It is hard to imagine the enormous complexity of the human brain on a cellular level. There are an estimated 100 billion neurons in the adult brain, and an estimated 10 to 100 trillion structures (called synapses) where these neu- rons communicate with each other. A cubic millimeter of cerebral cortex alone contains roughly a billion synapses!11

Not surprisingly, the brain is the most complex organ of the body. So how can we possibly begin to understand the brain amidst such complexity? Or rather, are our own brains sophisticated enough to understand how our brains work?

Fortunately, the task is not as insurmountable as it seems. The neuron itself, as the basic unit of the nervous system, can be understood in relatively simple terms. Imagine the neuron at any moment in time as a tiny device that is either on or off, like a light switch. There is no intermediate state. In this respect, the nervous system is digital like a computer, since a computer consists sim- ply of electrical circuits that are permitted only two states, open or closed. In terms of the neuron, the “on” state is accomplished by the generation of a nerve impulse. Just as the neuron is the basic unit that forms the structure of the nervous system, the nerve impulse is the basic event that forms the language of the nervous system.

The unique role of the neuron is to receive infor- mation and to transmit information, a task that it car- ries out through its three principal components: the cell body, the dendrites, and the axon (Figure 3.5). The cell body comprises the bulk of the neuron and contains the nucleus and other elements that various other types of cells in the body (such as muscle cells, skin cells, and blood cells) also exhibit.

The feature that makes the neuron specialized for communication purposes is the appendages that extend from the cell body, some of them rather short and one quite long. The short ones are called dendrites and rep- resent the part of the neuron that receives information from the outside. The long appendage, called the axon, is the part that transmits information outward. The axon is essentially the carrier of the messages of the neuron.

When a nerve impulse is generated, it travels down the length of the axon at speeds up to 120 meters per second (roughly 270 miles per hour) until it reaches the axon’s end point. If we followed the nerve impulse down the length of the axon, starting from the cell body (sometimes a distance of up to three feet), we would see

Quick Concept Check 3.2

Understanding Drugs and Brain Functioning Check your understanding of the relationship between certain psychoactive drugs and functions of the brain by matching the part of the brain most likely to be affected by a given drug, given the description of its behavioral effects.

psychoactive drug effects

brain areas affected

1. Drug X changes the pattern of your sleep.

cerebral cortex

2. Drug Y interferes with your intellectual functioning.

medulla

3. Drug Z raises your general arousal level.

cerebellum

4. Drug U interferes with your ability to control food intake.

pons

5. Drug V interferes with your ability to breathe.

hypothalamus

6. Drug W makes you very dizzy.

reticular formation

Answers: 1. pons 2. cerebral cortex 3. reticular formation 4. hypothalamus 5. medulla 6. cerebellum

Chapter 3 How Drugs Work in the Body and on the Mind ■ 75

that, toward its end, the axon diverges like the branches of a tree. At the terminal point of each of these branches are small button-like structures called synaptic knobs. If nothing else happened here, the nerve impulse would sputter out like a wet fuse. But, of course, there is more to the story. By virtue of junctures between neurons called synapses, nerve impulses from one neuron can influ- ence the emission of nerve impulses in other neurons. This process is referred to as neuronal communication.

Neuronal Communication Located inside the synaptic knob are synaptic vesicles (basi- cally container units) that store millions of chemical mol- ecules called neurotransmitters. When the nerve impulse reaches the synaptic knob, it causes neurotransmitters to be released out of the vesicles. The neurotransmitters then migrate across the intervening gap between two neurons and quickly arrive at the other (“receiving”) side.

On the surface of the receiving neuron are special structures called receptors, The receptor can be imag- ined as having an internal shape that is specifically designed to match the external shape of the neurotrans- mitter. The successful communication of neurons at the synapse depends on the neurotransmitter and recep- tor shape “fitting together,” like a key successfully fitting into a lock (Figure 3.6). If there is a “match,” receptor

F I g u r e 3 . 5

Basic structure of a neuron. The axon is shown surrounded by the myelin sheath, which increases the transmission speed of nerve impulses.

Axon

Myelin sheath

Cell body

Dendrites

Synaptic knobs

synapse (SIN-apse): The juncture between neurons. It consists of a synaptic knob, the intervening gap, and receptor sites on a receiving neuron.

neurotransmitter: A chemical substance that a neu- ron uses to communicate information at the synapse.

Neurotransmitter A

Neurotransmitter A

Neurotransmitter B

Neurotransmitter B

Match

Match

No match

No matchReceptor

Receptor

Receptor

Receptor

F I g u r e 3 . 6

Communication between neurons depends on a match between neurotransmitter and receptor. The “key and lock” concept is a simplified way of understanding the general process of receptor binding.

76 ■ Part One Drugs in Society/Drugs in Our Lives

binding has occurred. Neuron A has now communi- cated with Neuron B.

Receptor binding produces one of two possible changes in the receiving neuron: excitation or inhibition. Excitation means that there is an increase in the number of nerve impulses per second that are emitted by the receiving neuron; inhibition means that there is a decrease. Whether receptor binding produces an excitatory or inhibitory effect depends on the nature of the receptor at the synapse. Some neurotransmitters are referred to as excitatory neurotrans- mitters because they bind to excitatory receptors; other neurotransmitters are referred to as inhibitory neurotrans- mitters because they bind to inhibitory receptors.

Having produced either an excitatory or inhibitory effect, neurotransmitters now return back to the vesicles in the synapse knob. Once this is accomplished, condi- tions at the synapse are ready for the process of neuronal communication to begin once more.

Drug Influences on Neuronal Communication

With these facts in mind, we can understand the influ- ence of psychoactive drugs on brain functioning in terms of the three basic stages of neuronal communica- tion: (1) neurotransmitter release, (2) receptor binding, and finally (3) the “returning back” of the neurotrans- mitter to the synaptic knob for future use.

■ One way that drugs can influence the functioning of neurons is by increasing the quantity of neurotrans- mitters released into the synapse from the synaptic knob. With more neurotransmitter molecules at work, excitatory or inhibitory changes in the receiv- ing neuron can be enhanced. Some drugs bear such a close structural resemblance to a neurotransmitter that they can arrive at the receptor and act as though they are the “real thing.” In other words, a greater degree of excitation or inhibition can occur because both the drug and the neurotransmitter are arriving at the receptor sites at the same time (and the receptors are unable to tell the difference).

■ A second way that drugs can influence the function- ing of neurons is by diminishing the likelihood of receptor binding. Some drugs accomplish this by blocking the neurotransmitter at the receptor site. In an analogy to football, the drug acts like a defensive back preventing a wide receiver from catching a for- ward pass from the quarterback.

■ Because neurons emit nerve impulses in very rapid succession, neurotransmitters cannot remain in the

receptor for more than a millisecond or two. In most cases, once the neurotransmitter binds to the receptor, it is simply expelled and transported in its intact form back to the synaptic knob. This process is referred to as reuptake (Figure 3.7).

■ The speed of reuptake can be modified by a specific drug, with important consequences for neuronal communication. If reuptake is slowed down a bit, the neurotransmitter remains in the receptor longer, and receptor binding is enhanced. Conversely, if reuptake is sped up a bit, the neurotransmitter remains in the receptor a shorter period of time, and receptor bind- ing is diminished. Cocaine and some antidepressant drugs accomplish their stimulant effects (see Chap- ters 4 and 15) by slowing down or even blocking the reuptake process.

■ In some cases, receptor binding is followed by the neurotransmitter being broken apart by specific en- zymes in the synapse and “reconstructed” back in the synaptic knob for future use. Drugs that inhibit these enzymes cause the breakdown process to be dimin- ished. The neurotransmitter remains longer in the receptor, and receptor binding is enhanced.

Major Neurotransmitters in Brief: The Big Seven More than fifty neurotransmitters have been identi- fied as functioning in the brain, but fortunately we can understand the essential neurochemical basis for psy- choactive drugs and the impact on behavior on the basis of the seven most prominent neurotransmitters.

Acetylcholine was the first molecule to have been firmly established as a neurotransmitter. There are two types of receptors that are sensitive to acetylcholine.

The first type, muscarinic receptors, so named because they are responsive to the drug muscarine, are located in the parasympathetic autonomic nervous sys- tem. If a drug is antimuscarinic, that means it interferes with the role of acetylcholine in stimulating parasympa- thetic reactions of the body. Examples are atropine and scopolamine (see Chapter 6). A short-acting atropine-like solution, topically applied to the eyes, is used by oph- thalmologists during an eye examination to cause the

reuptake: The process by which a neurotransmitter returns from the receptor site to the synaptic knob.

acetylcholine (a-See-til-KOH-leen): A neurotransmitter active in the parasympathetic autonomic nervous sys- tem, cerebral cortex, and peripheral somatic nerves.

Chapter 3 How Drugs Work in the Body and on the Mind ■ 77

pupils to dilate by inhibiting the parasympathetic ten- dency for the pupils to constrict, making it possible to examine the retina. The second type, nicotinic receptors, so named because they are responsive to nicotine (see Chapter 10), are found near the end points of motor neurons, where skeletal muscles are innervated, as well as throughout the cerebral cortex. Some antinicotinic drugs, such as the poison curare, affect these motor neu- rons so dramatically that the body can become paralyzed within seconds. Deficiencies in acetylcholine or in nic- otinic receptors have been tied to Alzheimer’s disease, a condition resulting in memory loss and disorientation.

Norepinephrine, the second major neurotransmit- ter, is concentrated in the hypothalamus and limbic system but is also found throughout the brain. In the peripheral nervous system, it is the principal neurotrans- mitter for sympathetic autonomic activation, but its role there is independent of its effects in the brain. Norepi- nephrine helps to regulate our mood states; Chapter 15 will discuss how drugs that boost the levels of norepi- nephrine also help relieve symptoms of depression.

Dopamine, the third major neurotransmitter, affects three important aspects of our behavior. The first

aspect is motor control: the ability to start a movement when we want to; to stop it when we want to; and to exe- cute the movement in a smooth, precisely determined manner. Specifically, Parkinson’s disease is a result of a degeneration of dopamine-releasing neurons in the substantia nigra of the midbrain. The second aspect is emotionality. Problems in dopamine-releasing neurons in the cortex and limbic system are strongly suspected to be at the root of schizophrenia. The role of dopamine in schizophrenia and efforts to develop drugs that relieve schizophrenic symptoms will be discussed in Chap- ter 15. Third, as we will see shortly, dopamine in the brain plays a major role in producing the craving that encourages a continuing pattern of compulsive drug- taking behavior.

Receptor sites

Change in potential, leading to either excitation or inhibition

Synaptic vesicles

Neurotransmitter molecules

REUPTAKE

RELEASE BINDING

1. A nerve impulse stimulates the release of neurotransmitters across the synapse.

2. Neurotransmitters bind themselves to receptor sites on the surface of another neuron, causing a change in electrical

potential.

3. After receptor binding has occurred, neurotransmitters are returned into the

synaptic knob in a process called reuptake. If the process of reuptake is slowed down a bit, neurotransmitters will remain longer in the receptor site and produce a stronger

receptor-binding effect.

F I g u r e 3 . 7

A close-up view of a single synapse, showing the sequence of major events in neuronal communication: (1) neurotransmitter release, (2) receptor binding, (3) reuptake.

norepinephrine (NOr-ep-ih-NeH-frin): A neurotrans- mitter active in the sympathetic autonomic nervous system and in many regions of the brain.

dopamine (DOPe-ah-meen): A neurotransmitter in the brain whose activity is related to emotionality and motor control.

78 ■ Part One Drugs in Society/Drugs in Our Lives

Serotonin, the fourth neurotransmitter, is concen- trated in the pons and medulla, in the limbic system, and in the cortex. At the level of the hindbrain, sero- tonin plays an important role in regulating patterns of sleep. At the level of the limbic system, it shares with norepinephrine responsibility for establishing appropri- ate mood levels, avoiding wild swings upward that result in mania or wild swings downward that result in depres- sion. As you can predict, many drugs that relieve mania and depression act upon serotonin-releasing neurons. Several hallucinogenic drugs, such as LSD, stimulate serotonin-releasing neurons in the cortex, a topic that will be explored further in Chapter 6.

It should be noted that the technical name for sero- tonin is 5-hydroxytryptamine (abbreviated 5-HT), and receptors sensitive to serotonin are frequently called 5-HT receptors. Being aware of this terminology is help- ful when reviewing the research literature on serotonin in neuronal communication (see earlier section), but it will not be employed here. Any future references to this neurotransmitter will be expressed using the name sero- tonin, rather than its biochemical equivalent.

Gamma aminobutyric acid (GABA), the fifth neurotransmitter, is an important inhibitory neurotrans- mitter throughout the brain. Antianxiety medications, often referred to as tranquilizers, stimulate GABA-releas- ing neurons, providing a reduction in feelings of stress and fear, as will be discussed in Chapter 13. Since this neurotransmitter is a major source of inhibitory control, it should not be surprising that GABA deficiencies are associated with an increased tendency to suffer epileptic seizures.

Glutamate, the sixth major neurotransmitter, is also widely distributed throughout the brain and func- tions as an excitatory neurotransmitter in the brain, causing neurons to be more active. There is increas- ing evidence of a close connection between glutamate activity and the abuse potential of several psychoac- tive drugs. The exact relationship, however, appears to depend on the specific subtype of glutamate receptor. On the one hand, the action of two dissociative anes- thetics with hallucinogenic properties, phencyclidine (PCP, also known as angel dust) and ketamine, is asso- ciated with the blocking of one subgroup of glutamate receptors (see Chapter 6). On the other hand, recent pharmacological research has pointed to the activation of another subgroup of glutamate receptors as a critical element in drug craving and drug-abuse relapse with respect to cocaine, nicotine, alcohol, and heroin. As a result, the current development of new medications that block glutamate receptors of the latter type shows great promise in drug-abuse treatment.12

The seventh major neurotransmitter is actually a group of neurotransmitters, collectively known as endor- phins. Because they bear a remarkable resemblance to morphine and other opioids, endorphins act as natural brain-produced painkillers (see Chapter 5). Another group of brain-produced chemicals called endocannabinoids bear a close resemblance to the active ingredient in mari- juana (see Chapter 7). An understanding of neurochemi- cals such as endorphins and endocannabinoids help to shed light on the mechanisms for the psychoactive effects of opioids and marijuana respectively (Drugs . . . in Focus).

Physiological Aspects of Drug-Taking Behavior

There are three important concepts related to drug-tak- ing behavior that arise from the physiology of the nervous system. The first is the blood–brain barrier, the second is the physiological basis for drug tolerance, and the third is the current hypothesis that psychological dependence is directly related to activity in a specific area of the brain.

The Blood–Brain Barrier Mentioned earlier in the chapter was a barrier that restricts the passage of drugs and other molecules from the bloodstream to the brain. This exclusionary system is called the blood–brain barrier. Because it is impor- tant to maintain a level of stability in the brain, we are quite fortunate that this “gatekeeper” keeps the envi- ronment of the brain free from the biochemical ups and downs that are a fact of life in the bloodstream. The key factor in determining whether a drug passes

serotonin (Ser-ah-TOH-nin): A neurotransmitter in the brain whose activity is related to emotionality and sleep patterns.

gamma aminobutyric acid (gABA) (gAM-ma a- MeeN-o-byoo-Teer-ik ASS-id; gAB-AH): An inhibitory neurotransmitter in the brain. Antianxiety drugs tend to facilitate the activity level of GABA in the brain.

glutamate (glu-ta-mate): An excitatory neurotrans- mitter in the brain. Glutamate receptors are associ- ated with actions of PCP and ketamine and with feelings of drug craving.

endorphins (en-DOr-fins): A class of chemical sub- stances, produced in the brain and elsewhere in the body, that mimic the effects of morphine and other opioid drugs.

blood–brain barrier: A system whereby some sub- stances in the bloodstream are excluded from enter- ing the nervous system.

Chapter 3 How Drugs Work in the Body and on the Mind ■ 79

through the blood–brain barrier is the degree to which that drug is fat-soluble.

Despite the obstacles, many types of drugs easily pass into the brain: nicotine, alcohol, cocaine, barbitu- rates, and caffeine, to name a few. Penicillin, by con- trast, does not cross the blood-brain barrier because it is not fat-soluble. Consequently, penicillin can be used as an antibiotic treatment only for infections outside the brain.13

The presence of a blood–brain barrier is an issue not only for the study of psychoactive drugs but also

for certain medical treatments. For example, one of the effective treatments for Parkinson’s disease is administration of the drug L-Dopa, a shortened name for levodopa. The reason for using this drug stems from the root cause of Parkinson’s disease: a

Drugs . . . in Focus

Endorphins, Endocannabinoids, and the “Runner’s High” There has been great progress in our understanding of how specific psychoactive drugs (opioids and marijuana, respec- tively) work at a biochemical level in the brain. The essen- tial message from neuroscience research is that these drugs produce their physiological and behavioral effects by virtue of triggering chemicals and receptors that have existed in our brains throughout our evolutionary history. They shed light on how the brain works on a day-to-day basis and at crucial times in our lives.

Endorphins, for example, have been related to the underlying process of pain control. Under stressful circum- stances, people can become temporarily analgesic (rela- tively insensitive to pain) without any external drugs. There are well-documented cases of soldiers who have ignored their injuries during the heat of battle, athletes who are unaware of their pain until the game is over, and individu- als in primitive societies who endure painful religious ritu- als without complaint. Increased levels of endorphins are believed to contribute to these phenomena.

In another line of evidence, the effects of the Chinese technique of analgesic acupuncture (the inserting of needles into the skin at precisely defined points in the body to relieve pain) have been found to be completely reversible by naloxone (a specific antagonist to endorphins, see Chapter 5). It is reasonable, therefore, to conclude that the beneficial effects of acupuncture result from increased levels of endorphins.

Endorphin levels measured in the placental blood- stream of pregnant women near to the time of childbirth are greatly elevated from levels normally present in non- pregnant women, and they reach a peak during labor itself.

It is believed that, as a result, women in labor are enduring less pain than they would experience if these endorphin levels were unchanged. In other words, endorphins may protect them against an even greater amount of discomfort.

With respect to the “runner’s high,” the feeling of calm and euphoria that many individuals report follow- ing prolonged exercise, endorphins may play a role. But recently, attention has been drawn to another group of brain produced chemicals called endocannabinoids, so called because they mimic the physiological effects of can- nabis products such as marijuana. The endo prefix in both endorphins and endocannabinoids refers to the fact that these chemicals are produced and operate internally rather than consequences of drugs brought in from outside the nervous system.

It has been found that fifty minutes of hard running on a treadmill or riding on a stationary bicycle significantly increases increased levels of endocannabinoids in the blood. Since endocannabinoids are small molecules, they can pass through the blood-brain barrier (to be described later in the chapter) and produce the calming and free- form sense of well-being that is associated with marijuana. Experiments have yet to be carried out that would establish a causal link between activation of endocannabinoids in the brain and the subjective experience of a “run- ner’s high,” but the circumstantial evidence is certainly intriguing.

Sources: Boecker, H.; Sprenger, T.; Spilker, M.B.; Henriksen, G.; et al. (2008). The runner’s high: Opioidergic mecha- nisms in the human brain. Cerebral Cortex, 18, 2325–2531. Dietrich, A., and McDaniel, W.F. (2004). Endocannabinoids and exercise. British Journal of Sports Medicine, 38, 536-541.

endocannabinoids (eN-doh-ca-NAB-ih-noids): Brain- produced chemicals that mimic the effects of the active ingredient in marijuana and other cannabis products.

80 ■ Part One Drugs in Society/Drugs in Our Lives

dopamine deficiency in the substantia nigra. Tak- ing dopamine itself is of no help, since its lack of fat- solubility excludes it from getting to the brain. Fortunately, L-Dopa, a metabolic precursor to dopa- mine, is fat-soluble. Therefore, L-Dopa can enter the brain and then change into dopamine. As a result, there is a rise in dopamine levels in the brain, and the symptoms of Parkinson’s disease are relieved. Unfor- tunately, as dopamine receptors continue to degener- ate over a period of years, L-Dopa treatment becomes increasingly ineffective.14

It has recently become possible to create fat- soluble molecules in the laboratory rather than find- ing them in nature. Pharmacologists have succeeded in combining protein-based drugs that are presently excluded by the blood–brain barrier with a fatty acid, enabling the drugs to slip through into the brain. It may be possible in the future to design special pro- teins (“smart proteins”) that not only ferry drugs across the barrier but also regulate the release of the drugs once they are in the brain.15

Biochemical Processes Underlying Drug Tolerance The last chapter considered the phenomenon of drug tolerance as a behavioral effect accomplished through Pavlovian conditioning. Tolerance can also be exam- ined in terms of two types of physiological processes, one occurring in the liver and the other occurring in the neuron itself.

In the first type, called metabolic (dispositional) tolerance, a drug may facilitate, over repeated adminis- trations, the processes that produce the drug’s biotrans- formation in the liver. The rate of alcohol elimination, for example, increases over time if alcohol is ingested repeatedly over an extended period. When the liver breaks down the drug faster than it had initially, a smaller amount is left available for absorption into the blood. In the case of alcohol, the habitual drinker feels less of an alcoholic effect and compensates by increas- ing the amount consumed.

In the second type of physiological process, called cellular (pharmacodynamic) tolerance, changes occur in the synapses of neurons themselves. Receptors that have been stimulated by the drug over time may become less sensitive to neurotransmitters that ordinar- ily affect them. As a result, the excitatory or inhibitory effect on the receiving neuron may be diminished. It is important to note that repeated blocking of recep- tors by a drug over time may cause a compensatory

Quick Concept Check 3.3

Understanding Cross-Tolerance and Cross-Dependence Check your understanding of cross-tolerance and cross- dependence by answering the following questions. Sup- pose you have two receptors in the brain, as shown here.

Drug A

Drug B

Neuro- transmitter

K

Drug C

Drug D

Receptor X Receptor Y

Neuro- transmitter

L

Notice that Receptor X has three binding sites, one for drug A, one for drug B, and one for neurotransmitter K. Receptor Y also has three binding sites, one for drug C, one for drug D, and one for neurotransmitter L.

On the basis of this information, indicate whether the following pairs of drugs show cross-tolerance and cross-dependence with each other.

1. drug A and drug B yes no

2. drug A and drug C yes no

3. drug B and drug C yes no

4. drug C and drug D yes no

5. drug B and drug D yes no

6. drug A and drug D yes no

Answers: 1. yes 2. no 3. no 4. yes 5. no 6. no

reaction, such as an increase in the number of recep- tors or an increase in the amount of neurotransmitter released.16

Instances of cross-tolerance and cross-dependence can be explained by the fact that we are dealing with multiple drugs that bind to the same receptors in the brain. Imagine that two or more drugs activated dif- ferent sites on the same receptor; the receptor itself would then not be able to “tell them apart.” As far

Chapter 3 How Drugs Work in the Body and on the Mind ■ 81

as the receptor was concerned, the effect would be the same. The neuronal effects of the drugs over an extended period of time would be equivalent and interchangeable, producing the effects of cross- tolerance and cross-dependence. In general, drugs that have similar psychoactive effects share common receptors.

Physiological Factors in Psychological Dependence Amphetamines, cocaine, heroin, alcohol, and nico- tine may be very different from a pharmacological standpoint, but they are remarkably similar in the way people and animals react to them. There is a tremen- dous feeling of satisfaction as these drugs enter the bloodstream and the brain, and an intense craving for repeating the experience. The parallels are numerous enough to suggest the existence of a common physio- logical process in the brain that links them all together. It is not a coincidence that there is a system of neurons near the hypothalamus and limbic system that animals will work hard to stimulate electrically. We cannot say how they are feeling at the time, but their behav- ior indicates that they want to “turn on” this region of their brains.

Two of the key elements in the rewarding effect of these psychoactive drugs are dopamine and a grouping of neurons lying in a region of the limbic system called the nucleus accumbens. When labora- tory animals are injected with amphetamines, heroin, cocaine, alcohol, or nicotine, for example, there is a release of dopamine in the nucleus accumbens, and since dopamine acts as an inhibitory neurotransmit- ter, the activity level of neurons in the nucleus accum- bens goes down.

Administration of any substance that interferes with the action of dopamine in this region eliminates the desire of animals to work for the self-administration of these abused drugs. Although we cannot say, of course, that these animals no longer experience feel- ings of craving as a result, you will recall that self- administration behavior in animals closely parallels the pattern of human behavior that characterizes psy- chological dependence. Therefore, these studies can be used to understand the neural changes caused by drug abuse. Considering the evidence now in hand, a persuasive argument can be made that dopamine- related processes in the nucleus accumbens underlie the reinforcing effects of many abused drugs. There is

also research showing an involvement of the nucleus accumbens with compulsive gambling and compulsive eating disorders.17

It is not hard to see the applications to the real- world treatment of drug dependence. Drugs that affect activity in the nucleus accumbens are cur- rently being developed to reduce the feelings of crav- ing that cause drug-dependent individuals to relapse (Health Line).18

Research on the influence of dopamine and dopamine receptors in drug dependence has pro- vided an insight into the question of why some individuals may be more susceptible than oth- ers to drug-taking behavior. In one study, twenty- three drug-free men with no history of drug abuse were given doses of methylphenidate (brand name: Ritalin), a psychoactive stimulant when ingested by adults. Twelve of the men experienced a pleas- ant feeling, nine felt annoyed or distrustful, and two felt nothing at all. Measurements of a subclass of dopamine receptors in the brains of these sub- jects showed a consistent pattern. The men with the least concentration of dopamine receptors were the ones experiencing pleasant effects. It is reasonable to hypothesize that those individuals with the fewest dopamine receptors might be the most vulnerable to drug abuse. A reasonable hypothesis is that their drug-taking behavior as a matter of compensating for an inadequate number of dopamine receptors neces- sary to experience pleasurable feelings without drugs (see Portrait, page 84).19

We now understand that individual differences observed in dopamine receptor concentrations are, in part, genetically based. In the case of nicotine, it is estimated that genetics accounts for about 75 percent of the inclination to begin smoking, for about 60 per- cent of the tendency to become dependent on nico- tine, and for about 54 percent of the ability to quit. Analyses of the human genome have revealed spe- cific gene sites that increase the risk of alcohol abuse and the risk of abuse of a variety of illicit substances, including marijuana.

On the other hand, it is clear that there is an inter- play between genetic and environmental influences in this area, and the total picture is bound to be complex.

nucleus accumbens (NeW-clee-us ac-CuM-buns): A region in the limbic system of the brain considered to be responsible for the rewarding effects of several drugs of abuse.

82 ■ Part One Drugs in Society/Drugs in Our Lives

Health Line Drug Craving and the Insula of the Brain

They were thirty-two former cigarette smokers, reporting a minimum of five cigarettes a day for two years or more. They had all suffered some degree of brain injury. They had all reported how difficult it was to stop smoking. Six- teen of the smokers, however, found themselves capable of stopping easily following their injury. Why were these particular sixteen individuals so lucky?

It turns out that it was considerably more likely for these smokers to quit smoking if brain damage had included a prune-shaped area under the frontal lobes of the cerebral cortex called the insula. Twelve out of thir- teen with insula damage quit easily, whereas only four out of nineteen with damage that did not include the insula were able to do so. The insula-damage group had an odds ratio, regarding their likelihood of smoking cessation, of approximately 22 (see Chapter 2). In other words, they were twenty-two times more likely to stop cigarette smok- ing than the non-insula-damage group.

This relatively small study, reported in 2007, has had a major impact on our understanding of the neurological basis for drug dependence. A neuroimaging study in a group of drug abusers, for example, has shown increased

insula activity to be correlated with subjective feelings of drug craving when they viewed a series of drug- related images. In a study of animals made dependent on amphetamine, the inactivation of the insula in their brains has been shown to prevent their urge to seek out amphetamine in their laboratory environment. An accu- mulating body of research points to the importance of the insula in the neural circuitry that not only maintains sub- stance dependence but also the complex decision-making process that underlies urges for pleasurable outcomes in our lives.

Sources: Carey, B. (2007, January 26). In clue to addic- tion, a brain injury halts smoking. New York Times, pp. A1, A18. Contreras, M.; Ceric, F.; and Torrealba, F. (2007). In- activation of the interoceptive insula disrupts drug craving and malaise induced by lithium. Science, 318, 655–658. Naqvi, N., and Bechara, A. (2010). The insula and drug addiction: An interoceptive view of pleasure, urges, and decision-making. Brain Structure and Function, 214, 435– 450. Naqvi, N. H.; Rudrauf, D.; Damasio, H.; and Bechara, A. (2007). Damage to the insula disrupts addiction to cigarette smoking. Science, 315, 531–534.

For example, genetic influences in substance abuse in general have been found to be more prominent among people in early to middle adulthood and less prominent among adolescents, for whom social envi- ronmental factors are dominant.20

Psychological Factors in Drug-Taking Behavior

This chapter has considered the physiological effects of psychoactive drugs, down to the level of a single neuron in the brain. It has also pointed out that cer- tain physiological factors (such as weight and gender) must be taken into account to predict particular drug effects. Yet even if we controlled these factors com- pletely, we would still frequently find a drug effect in an individual person to be different from time to time, place to place, and situation to situation. Predictions about how a person might react would be far from per- fectly accurate.

Therefore, a good way of thinking about an indi- vidual’s response to a particular drug is to consider the drug effect as a three-way interaction of the drug’s phar- macological properties (the biochemical nature of the substance), the individual taking the drug (set), and the immediate environment within which drug-taking behavior is occurring (setting) (Figure 3.8). Whether

This is literally “your brain on drugs.” PET scans from a drug-free subject (left), a detoxified cocaine abuser one month after detoxification (middle), and a detoxified cocaine abuser four months after detoxification (right). The absence of orange- colored areas in the PET scans in the middle and on the right indicates lower levels of dopamine activity.

Chapter 3 How Drugs Work in the Body and on the Mind ■ 83

one or more of these factors dominate in the final anal- ysis seems to depend on the dosage level. Generally speaking, the higher the drug dose, the greater the con- tribution made by the pharmacology of the drug itself; the lower the dose, the greater the contribution of indi- vidual characteristics of the drug-taker or environmental conditions.21

Expectation Effects One of the most uncontrollable factors in drug-taking behavior is the set of expectations a person may have about what the drug will do. If you believe that a drug will make you drunk or feel sexy, the chances are increased that it will do so; if you believe that smoking a marijuana joint makes you high, the chances are increased that it will. In the most extreme case, you might experience a drug effect even when the substance you ingested is completely inert—that is, pharmacologically ineffective. Any inert (inactive) substance is referred to as a placebo (from the Latin, “I will please”), and the physical reac- tion to it is referred to as the placebo effect.

Of course, the reverse is true as well. You can imag- ine the impact of negative expectations in drug-taking behavior. When feelings are strong that a drug will have

no effect on you, the chances are lessened that you will react to it.

The concept of a placebo goes back to the earli- est days of pharmacology. The bizarre ingredients prescribed in the Ebers Papyrus (see Chapter 1) were effective to the extent that people believed that they were effective, not as a consequence of any known fac- tor in these ingredients. No doubt, the placebo effect was strong enough for medical symptoms to diminish. During the Middle Ages, in one of the more extreme cases of the placebo effect, Pope Boniface VIII report- edly was cured of kidney pains when his personal phy- sician hung a gold seal bearing the image of a lion around the pope’s thigh.22 However, it would be a mis- take to think of the placebo effect as involving totally imaginary symptoms or totally imaginary reactions. Physical symptoms, involving specific bodily changes, can occur on the basis of placebo effects alone. How likely is it that a person will react to a placebo? The probability varies from drug to drug, but in the case of morphine, the data are very clear. A 1959 review of stud- ies in which morphine or a placebo was administered

Pharmacological properties of

the drug

Individual taking the drug (set)

Drug Effect

Immediate environment where drug-taking behavior

is occurring (setting)

F I g u r e 3 . 8

Viewing a psychoactive drug effect as a three-way interaction.

placebo (pla-See-bo): Latin term translated “I will please.” Any inert substance that produces a psycho- logical or physiological reaction.

The likelihood of a placebo effect is maximized when the patient has a substantial level of trust in the expertise of the physician prescribing a drug.

84 ■ Part One Drugs in Society/Drugs in Our Lives

in clinical studies of pain concluded that a placebo- induced reduction in pain occurred 35 percent of the time. Considering that morphine itself had a positive result in only 75 percent of the cases, the placebo effect was a very strong one.

In a more recent placebo study reported in 2008, volunteer subjects were asked to judge the intensity of electric shocks before and after ingesting a pill that con- tained no active ingredients. Half of the subjects were told the pill was a drug selling for $2.50 each, and the other half were told the pill cost a “discounted” ten cents. The percentage of subjects reporting a reduction in pain was greater with the expensive pill (85 percent) than with the cheaper pill (62 percent). In both cases, a placebo effect was observed. Higher-priced pills were assumed to be more effective than cheaper pills, even though in both cases they were physiologically inert.23

Evidently, the attitude that “you get what you paid for” is alive and well, even in the context of drug-taking behavior.

Unfortunately, it is difficult to predict exactly whether a person will react strongly or weakly to a placebo. We do know, however, that the level of enthusiasm of the prescribing physician plays a major role. In other words, the credibility of the messen- ger enhances the credibility of the message. In one study that varied the attitude of the physician toward a particular medication, negative attitudes toward the medication resulted in the least benefits, whereas positive attitudes resulted in the most. The color of a placebo can also be a factor. A yellow antidepres- sant pill is more likely to evoke a “sunnier” outlook on life; a red pill is more likely to have a stimulating effect; a green pill is more likely to reduce anxiety;

P O r T r A I T Nora D. Volkow—A Scientist-General in the War on Drugs

It is one thing to speculate about the effects of drug abuse on the brain, to assert that the transi- tion from initially being a voluntary drug user to becoming a compulsive drug user is a matter of subtle but significant brain changes. It is quite another thing to have shown the physi- cal effects themselves.

Using a brain scanning technique called positron emission tomography (PET), neural activity in the human brain can be captured in graphic detail (see images on page 82). Nora D. Volkow, Director of the National Institute on Drug Abuse (NIDA) and her research colleagues have shown that chronic cocaine abuse leads to the loss of about 20 percent of the dopamine receptors in the nucleus accumbens. This effect appears to be long-lasting, enduring for up to four months after the last cocaine exposure, even though the cocaine abuser no longer has cocaine in his or her system. Volkow estimates that a comparable decline in dopamine receptors would take at least 40 years to accomplish in a drug-free brain.

It is not surprising that the nucleus accumbens, with

its rich concentration of dopamine receptors, would be the site of this dramatic change. Dopamine and the nucleus accumbens have been associated with feelings of reward and pleasure in a wide range of behavioral activities, from drug use to compulsive exercising to gambling. The irony is that it may be precisely those individu- als who have fewer dopamine recep- tors who may be inclined to engage in drug-taking behavior in the first place; the drug exposure evidently makes the deficit worse.

But then there is a fundamental question: What creates the intense craving for specific drugs once an individual has been first exposed to them? An important clue can be found in the research of Anna R. Childress and her associates at the University of Pennsylvania. When chronic drug abusers were shown video segments of drug-associated paraphernalia (a picture of a syringe or a mound of white powder),

PET scans of their brains revealed increased activity in an area of the limbic system. It is reasonable to hypothesize that the association between activation of the limbic system and stimulation of dopamine- sensitive neurons in the nucleus accumbens may be a significant fac- tor in the triggering of drug craving in cases of chronic drug abuse.

Sources: Childress, A.R.; Mozley, D.; McElgin, W.; Fitzgerald, J.; Reivich, M.; et al. (1999). Limbic activation during cue-induced cocaine craving. American Journal of Psychiatry, 156, 11–18. Volkow, N.D.; Wang, G-J.; Fowler, J.S.; Logan, J.; Gatley, S.J.; Hitzemann, R.; et al. (1997). Decrease in striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature, 386, 830–833. Volkow, N., and Li, T.K. (2004, December). Drug addic- tion: The neurobiology of behaviour gone awry. Nature Reviews/Neuroscience, 963–970. Zuger, A.(2011, June 14). Nora D. Volkow: A general in the drug war. New York Times, pp. D1, D4.

Chapter 3 How Drugs Work in the Body and on the Mind ■ 85

Summary

How Drugs enter the Body ● There are four basic ways to administer drugs into the

body: oral administration, injection, inhalation, and absorption through the skin or membranes. Each of these imposes constraints on which kinds of drugs will be effectively delivered into the bloodstream.

How Drugs exit the Body ● Most drugs are eliminated from the body through uri-

nary excretion. Drugs are broken down for elimina- tion by the action of enzymes in the liver. An index of how long this process takes is called the elimination half-life.

Factors Determining the Behavioral Impact of Drugs ● Fa c t o r s t h a t i n f l u e n c e t h e p h y s i o l o g i c a l e f -

fect of a drug include the time elapsed since its

administration, drug interactions when it is admin- istered with other drugs at about the same time, and the personal characteristics of the individual consuming the drug.

● An individual’s weight, gender, and ethnic back- ground can play a definite role in the behavioral and physiological effects of a drug.

Introducing the Nervous System ● Understanding the organization of the nervous system

helps us to understand where psychoactive drugs are working in our bodies.

● The nervous system consists of the peripheral ner- vous system and the central nervous system, with the latter divided into the brain and the spinal cord. Autonomic nerves control our cardiac and smooth muscles to respond either to stress (sympathetic

double-blind: A procedure in drug research in which neither the individual administering a chemical sub- stance nor the individual receiving it knows whether the substance is the drug being evaluated or an active placebo.

and, not surprisingly, a pill with a trademark brand imprinted on it is more likely to be effective in gen- eral than a generic version.24

It is not at all clear how the placebo effect is accomplished. In the case of pain relief, there is evi- dence that we have the natural ability to increase lev- els of endorphins in the bloodstream and the brain from one moment to the next, but the nature of our ability to alter other important substances in our bodies is virtually unknown. Placebo studies have shown a 33 percent increase in lung capacity among asthmatic children who inhaled a bronchodilator containing a placebo instead of medication and the development of skin rashes in people who have been exposed to fake poison ivy, to name a few examples of placebo-induced physiological reactions. Placebo research forces us to acknowledge the potential for psychological control over physiological processes in our bodies.25

Drug Research Procedures Given the power of the placebo effect in drug-taking behavior, it is necessary to be very careful when carry- ing out drug research. For a drug to be deemed truly effective, it must be proved to be better not only in comparison to a no-treatment condition (a difference

that could conceivably be attributed to a placebo effect) but also in comparison to an identical-looking drug that lacks the active ingredients of the drug being evaluated. For example, if the drug under study is in the shape of a round red pill, another round red pill without the active ingredients of the drug (called the active placebo) must also be administered for comparison.

The procedures of these studies also have to be carefully executed. Neither the individual adminis- tering the drug or placebo nor the individual receiv- ing the drug or placebo should know which substance is which. Such precautions, referred to as a double- blind procedure, represent the minimal standards for separating the pharmacological effects of a drug from the effects that arise from one’s expectations and beliefs.26 We will return to the issue of interactions between drug effects and expectations in Chapter 8 when we consider behaviors associated with alcohol intoxication.

86 ■ Part One Drugs in Society/Drugs in Our Lives

Endnotes

1. Monaghan, P. (2012, March 2). Nota bene: This is your brain on drugs. Review of Lewis, M. (2012). Memoirs of an addicted brain. New York: Public Affairs. Phrase quotation from M. Lewis.

2. Public-service message, “Frying Pan.” Partners for a Drug-free America, New York, 1987.

3. Benson, H. A. E., and Watkinson, A. C. (2012). Topical and transdermal drug delivery: Principles and Practice. Hoboken, NJ: Wiley. Grilly, D. M., and Salamone, J. D. (2012). Drugs, brain, and behavior (6th ed.). Boston: Pearson Education, pp. 44–49. National Institute on Drug Abuse (20111, November). Nanotechnology

Key Terms

acetylcholine, p. 76 biotransformation, p. 64 blood–brain barrier, p. 78 central nervous system

(CNS), p. 69 cerebral cortex, p. 73 cross-dependence, p. 67 cross-tolerance, p. 67 dopamine, p. 77 double-blind, p. 85 elimination half-life, p. 66

endocannabinoids, p. 79 endorphins, p. 78 gamma aminobutyric acid

(GABA), p. 78 glutamate, p. 78 intramuscular (i.m.), p. 62 intranasal, p. 63 intravenous (i.v.), p. 62 latency period, p. 66 metabolite, p. 64 neuron, p. 72

neurotransmitter, p. 75 norepinephrine, p. 77 nucleus accumbens, p. 81 parasympathetic branch of

the autonomic nervous system, p. 70

peripheral nervous system, p. 69

placebo, p. 83 potentiation, p. 67 reuptake, p. 76

serotonin, p. 78 subcutaneous (s.c. or

sub-Q), p. 62 sublingual, p. 64 sympathetic branch of the

autonomic nervous system, p. 70

synapse, p. 75 synergism, p. 67 transdermal patch, p. 64

activation) or to demands for nurturance and renewal (parasympathetic activation).

understanding the Brain ● Within the brain are three major divisions: the hind-

brain, midbrain, and forebrain. The forebrain is the most recently evolved region of the brain; it controls the most complex behaviors and processes the most complex information.

● Many drugs affect all levels of the brain, in one way or another.

Neuronal Communication and Drug effects ● Understanding the functioning of neurons and their

interaction through neuronal communication helps us to understand how psychoactive drugs work in our bodies.

● In general, drugs work at the neuronal level by alter- ing the three basic stages of neuronal communication: (1) neurotransmitter release, (2) receptor binding, and (3) the returning of the neurotransmitter back to the synaptic knob for future use.

● While neuronal communication involves essentially only two kinds of messages, excitation or inhibition, there are dozens of neurotransmitters that accom- plish this task. The seven major neurotransmitters

are acetylcholine, norepinephrine, dopamine, serotonin, gamma aminobutyric acid (GABA), glutamate, and a group of neurochemicals called endorphins.

Physiological Aspects of Drug-Taking Behavior ● Three important issues need to be understood in

looking at the physiological effect of drugs: the ex- tent to which drugs pass from the bloodstream to the brain, the extent to which tolerance effects occur, and the extent to which a drug influences neuronal activity in the region of the nucleus accumbens in the brain.

Psychological Factors in Drug-Taking Behavior ● Although the physiological actions of psychoactive

drugs are becoming increasingly well understood, great variability in the effect of these drugs remains, largely because of psychological factors.

● The most prominent psychological factor is the influence of personal expectations on the part of the individual consuming the drug. The impact of expect ations on one’s reaction to a drug, a phenomenon called the placebo effect, is an import ant consideration in drug evaluation and research.

Chapter 3 How Drugs Work in the Body and on the Mind ■ 87

powers smart skin patch. NIDA Notes. Bethesda, MD: National Institute on Drug Abuse.

4. Julien, R. M.; Advokat, C. D.; and Comaty, J. E. (2011). A primer of drug action (12th ed.). New York: Worth, pp. 27–32.3. McKim, W. A., and Hancock, S. D. (2013). Drugs and behavior: An introduction to behavioral pharmacology (7th ed.). Boston: Pearson, pp. 18–24.

5. Lickey, M. E., and Gordon, B. (1991). Medicine and mental illness. New York: Freeman, p. 323.

6. Frezza, M.; DiPadova, C.; Pozzato, G.; Terpin, M.; Baraona, E.; and Lieber, C. S. (1990). High blood alcohol levels in women: The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. New England Journal of Medicine, 322, 95–99.

7. Nakawatase, T. V.; Yamamoto, J.; and Sasao, T. (1993). The association between fast-flushing response and alco- hol use among Japanese Americans. Journal of Studies on Alcohol, 54, 48–53.

8. Johnson, R. C., and Nagoshi, C. T. (1990). Asians, Asian-Americans and alcohol. Journal of Psychoactive Drugs, 22, 45–52. Levy, R. (2010). Medication use by ethnic and racial groups: Policy implications. Journal of Pharmaceutical Health Services Research, 1, 15–22.

9. Haiman, C. A.; Stram, D. O.; Wilkens, L. R.; et al. (2006). Ethnic and racial differences in the smoking- related risk of lung cancer. New England Journal of Medicine, 354, 333–342. Perez-Stable, E. J.; Herrera, B.; Jacob III, P.; and Benowita, N.L. (1998). Nicotine metabolism and intake in black and white smokers. Journal of the American Medical Association, 280, 152–156.

10. Perry, J. L.; Joseph, J. E.; Yang, J.; Zimmerman, R. S.; et al. (2011). Prefrontal cortex and drug abuse vulner- ability: Translation to prevention and treatment interven- tions. Brain Research Reviews, 65, 124–149.

11. Alonso-Nanclares, L.; Gonzalez-Soriano, J.; Rodriguez, J. R.; and DeFelipe, J. (2008). Gender differences in human cortical synaptic density. Proceedings of the National Academy of Sciences U.S.A., 105, 14615– 14619. Drachman, D. (2005). Do we have brain to spare? Neurology, 64, 2004–2005. Thompson, R. F. (1993). The brain: A neuroscience primer (2nd ed.). New York: Freeman, p. 3.

12. Heidbreder, C. A., and Hagan, J. J. (2005). Novel phar- macotherapeutic approaches to the treatment of drug addiction and craving. Current Opinion in Pharmacol- ogy, 5, 107–118. Kalivas, P. W. (2009). The glutamate homeostasis hypothesis of addiction. Nature Reviews Neuroscience, 10, 561–571.

13. Julien, Advokat, and Comaty, pp. 17–19 14. Grilly and Salamone, pp. 172–177. Whitten, L. (2010,

October). Medications that normalize brain gluta- mate reduce drug-seeking in rats. NIDA Notes, pp. 1, 13–15.

15. Kumar, P.; Wu, H.; McBride, J. L.; et al. (2007). Trans- vascular delivery of small interfering RNA to the central nervous system. Nature, 448, 39–43. Jeffrey, P., and Sum- merfield, S. (2010). Assessment of the blood-brain barrier in CNS drug discovery. Neurobiology of Disease, 37, 33–37.

16. Grilly and Salamone, pp. 103–108; Julien, Advokat, and Comaty, pp. 446–447.

17. Potenza, M. N. (2008). The neurobiology of pathologi- cal gambling and drug addiction: An overview and next findings. Philosophical Transactions of the Royal Society, Biological Sciences, 363, 3181–3189. Russo, S. J.; Dietz, D. M.; Dumitriu, D.; Morrison, J. R., et al (2010). The addicted synapse: Mechanisms of synaptic and structural plasticity in nucleus accumbens. Trends in Neuroscience, 33, 267–276.

18. Volkow, N. D.; Fowler, J. S.; Wang, G-J.; and Swanson J. M. (2004). Dopamine in drug abuse and addiction: Results from imaging studies and treatment implications. Molecular Psychiatry, 9, 557–569.

19. Volkow, N. D.; Wang, G-J.; Fowler, J. S.; Logan, J.; Gatley, S. J.; et al. (1999). Prediction of reinforcing responses to psychostimulants in humans by brain dopamine D2 receptor levels. American Journal of Psychiatry, 156, 1440–1443.

20. Agrawal, A., and Lynskey, M. T. (2008). Are there genetic influences on addiction? Evidence from family, adoption and twin studies. Addiction, 103, 1069–1081. Agrawal, A.; Pergadia, M. L.; Saccone, S. F.; Lynskey, M. T.; Wang, J. C.; et al. (2008). An autosomal linkage scan for canna- bis use disorders in the Nicotine Addiction Genetics Proj- ect. Archives of General Psychiatry, 65, 713–722. Kendler, K. S.; Schmitt, E.; Aggen, S. H.; and Prescott, C. A. (2008). Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood. Archives of General Psychiatry, 65, 674–682. Price, Uhl, G. R.; Qing-Rong, L.; Drgon, T.; Johnson, C.; et al. (2008). Molecular genetics of successful smoking cessation. Archives of General Psychiatry, 65, 683–693.

21. Goode, E. (1999). Drugs in American society (5th ed.). New York: McGraw-Hill College, p. 9.

22. Kornetsky, C. (1976). Pharmacology: Drugs affecting behavior. New York: Wiley, p. 23. Morris, D. B. (1999). Placebo, pain, and belief: A biocultural model. In A. Harrington (Ed.), The placebo effect: An interdisciplinary exploration. Cambridge, MA: Harvard University Press, pp. 187–207. Shapiro, A. K., and Shapiro, E. (1997). The powerful placebo: From ancient priest to modern physi- cian. Baltimore: Johns Hopkins University Press.

23. Beecher, H. K. (1959). Measurement of subjective responses: Quantitative effects of drugs. New York: Oxford University Press. Waber, R. L.; Shiv, B.; Carmon, Z.; and Ariely, D. (2008). Commercial features of placebo and therapeutic efficacy. Journal of the American Medical Association, 299, 1016–1017.

88 ■ Part One Drugs in Society/Drugs in Our Lives

24. Benedetti, F. (2002). How the doctor’s words affect the patient’s brain. Evaluation and the Health Professions, 25, 369–386.

25. De la Fuente-Fernández, R., and Stoessl, A. J. (2002). The biochemical bases for reward: Implications for the placebo effect. Evaluation and the Health Professions, 25, 387–398. Levinthal, C. F. (1988). Messengers of paradise: Opiates and the brain. New York: Anchor Press/

Doubleday. Talbot, M. (2000, January 9). The placebo prescription. New York Times Magazine, pp. 34–39, 44, 58–60. Wager, T. D. (2005). The neural bases of pla- cebo effects in pain. Current Directions in Psychological Science, 14, 175–179.

26. Quitkin, F. M. (1999). Placebos, drug effects, and study design: A clinician’s guide. American Journal of Psychiatry, 156, 829–836.

89

Part two

Legally restricted Drugs in our Society

C h a p t e r

4The Major Stimulants: Cocaine and Amphetamines

S.F. is a brilliant young physician attending a case confer-

ence at a metropolitan medical center where he is a resi-

dent. He has been on call for thirty-six hours and cannot

concentrate on the presentation. S.F. is lonely, depressed,

and overworked. All he can think about is his fiancée,

Martha, who is several hundred miles away. He knows that

her father will not permit her to marry until he is able to

support her, and with his debts and meager salary, that

could take years.

He excuses himself from the conference, takes a

needle syringe from the nurses’ station, and locks him-

self in a bathroom stall. He fills the syringe with cocaine

and plunges the needle into his arm. Within seconds,

the young doctor feels a rush of euphoria. His tears dry

up; he regains his composure and quickly rejoins the

conference.

—The date is 1884, the place is Vienna, and the physician is Sigmund Freud.

After you have completed this chapter, you should have an understanding of

▶ The history of cocaine

▶ How cocaine works in the brain

▶ Patterns of cocaine abuse

▶ Treatment programs for cocaine abuse

▶ The history of amphetamines

▶ How amphetamines work in the brain

▶ Patterns of methamphetamine abuse

▶ Stimulant treatment for attention-deficit/hyperactivity disorder (ADHD)

90 ■ Part two Legally restricted Drugs in our Society

The time, place, and identity of S.F. in this fic- tionalized clinical vignette are based on the life of Sig- mund Freud. It may have surprised you to know that the founder of psychoanalysis started out as a physician interested more in the workings of the brain and the stimulant effects of cocaine than the deep recesses of the unconscious mind.1 It is worth commenting that the year could have been 1984 (or any other year since then) instead of 1884, and the individual involved could have been anyone twenty-eight years old, as Freud was at the time, or some other age. Freud was extremely lucky; he never became dependent on cocaine, although a close friend did—and countless numbers of people have suc- cumbed to cocaine dependence since Freud’s time.

The story of cocaine is both ancient and mod- ern. Although its origins stretch back more than four thousand years, cocaine abuse continues to represent a major portion of the present-day drug crisis. For this reason, it is important to understand its history, the properties of the drug itself, and why it has the abil- ity to control and ultimately, in many cases, destroy a person’s life. This chapter will focus not only on cocaine but also on another group of stimulant drugs referred to collectively as amphetamines, the most prominent example being methamphetamine (meth). Although cocaine and amphetamines are distinct in terms of their pharmacology (their characteristics as

biochemical substances), there are enough similari- ties in their behavioral and physiological effects to warrant their being discussed together. The emphasis will be on issues surrounding abuse and dependence. With respect to amphetamines and amphetamine-like drugs, we will examine an important medical applica- tion, the treatment for attention-deficit/hyperactivity disorder (ADHD).

In general, cocaine and amphetamines represent two major classes of psychoactive stimulants, drugs that energize the body and create intense feelings of eupho- ria. Other, less powerful stimulants, such as nicotine, caffeine, and clinical antidepressants, will be discussed in later chapters.

The History of Cocaine

Cocaine is derived from small leaves of the coca shrub (Erythroxylon coca) grown primarily in the high-alti- tude rain forests and fields that run along the slopes of the Peruvian and Bolivian Andes in South America, although coca cultivation can be found in other regions of the world with similar climate and soil conditions.

Like many other psychoactive drugs, cocaine use has a long history. We can trace the practice of chew- ing coca leaves, which contain about 2 percent cocaine, back to the Inca civilization, which flourished from the thirteenth century until its conquest by the Spaniards in 1532, as well as to other Andean cultures dating back five thousand years. According to tradition, coca was a gift from the god Inti to the Incas, allowing them to endure a harsh life in the Andes without suffering.2

To this day, coca chewing is part of the culture of this region. It is estimated that about 2 million Peruvian men (called acullicadores) who live in the Andean high- lands, representing 90 percent of the male population in that area, chew coca leaves.3 Coca is blended with chalk, lime, and ash to achieve the desired effects, whether the goal is to fight fatigue or simply relax with friends.4

This age-old practice produces few instances of tox- icity or abuse. The reason lies in the very low doses of cocaine that chewed coca leaves provide; in this form, absorption from the digestive system is slow, and rela- tively little cocaine enters the bloodstream and is dis- tributed to the brain (Chapter 3). A much more serious problem is the availability of a coca paste containing a much higher percentage of cocaine mixed with tobacco

cocaine: An extremely potent and dependence- producing stimulant drug derived from the coca leaf.

by the numbers . . .

3.9 million Americans, aged 12 or older, who re- ported in 2011 having used cocaine during the past year

625,000 Americans, aged 12 or older, who reported in 2011 having used crack cocaine during the past year

92 Percentage of 50 one-dollar bills randomly sampled from five U.S. cities that have been found to be contaminated with detectable levels of cocaine. Drug contamination begins with contact during drug deals and snorting, then transfers from bill to bill in money-counting machines in banks.

Sources: Substance Abuse and Mental Health Services Administration (2012). Results from the 2011 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Administration, Table 1.1A. Jenkins, A.J. (2001). Drug contamination of U.S. paper currency. Forensic Science International, 121, 189–193.

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 91

and smoked as a cigarette (referred to as a bazuco). Now delivered directly from the lungs to the brain, this form of coca ingestion is more likely to produce abuse and dependence. Making matters worse, dangerously high levels of kerosene, gasoline, and ether are involved in the coca-refining process and end up as adulterants in the cigarettes themselves.5

Cocaine in Nineteenth-Century Life Coca leaves were brought back to Europe from the Spanish colonies soon after the conquest of the Incas in 1533, but their potency was nearly gone after the long sea voyage. Perhaps, it was said at the time, the legend- ary effects of coca were merely exaggerations. Coca leaves were ignored for three hundred years.

By the late 1850s, however, the active ingredient of the coca plant had been chemically isolated. In 1859, the German chemist Alfred Niemann observed its anesthetic effect on his tongue and its bitter taste and named it “cocaine.” Interest in the drug was renewed, and by the 1860s the patent medicine industry in the United States and Europe (see Chapter 1) had lost no time in taking advantage of cocaine’s appeal.

By far the most successful commercial use of cocaine in the nineteenth century was a mixture of coca and wine invented in 1863 by a Corsican chemist and businessman, Angelo Mariani. We know now that the combination of

alcohol and cocaine produces a metabolite with an elimi- nation half-life up to five times longer than that of cocaine alone, so the intoxicating mixture tends last quite a while (Health Alert). No wonder “Vin Mariani” became an instant sensation and an enormous commercial success.

In a stroke of marketing genius, Mariani also invented the concept of celebrity endorsement. Over the next few decades, advertisements for Vin Mariani carried testimonials from satisfied customers such as U.S. President William McKinley, Thomas Edison, the surgeon general of the U.S. Army, General Ulysses S. Grant, actress Sarah Bernhardt, Jules Verne, the Prince of Wales, the czar of Russia, and Popes Pius X and

In the late nineteenth century, cocaine products were used by children as well as adults.

H e A l t H A l e r t !

Cocaine after Alcohol: the risk of Cocaethylene toxicity The risks of dying from cocaine arise from the drug’s powerful excitatory effects on the body, such as abnormal heart rhythms, labored breathing, and increased blood pressure. The toxicity potential for any of these toxic reac- tions is unfortunately increased when alcohol is already in the bloodstream. The biotransformation of cocaine and alcohol (ethanol), when they are ingested in combination, produces a metabolite called cocaethylene. One effect of cocaethylene is a three- to fivefold increase in the elimina- tion half-life of cocaine. As a result, cocaine remains in the bloodstream for a much longer time. More important, cocaethylene has a specific excitatory effect on blood pres- sure and heart rate that is greater than that produced by cocaine alone.

The combination of alcohol and cocaine is associ- ated with a prolonged and enhanced euphoria, but it also

brings an eighteen- to twenty-fivefold increased risk of immediate death. The fact that 62 to 90 percent of cocaine abusers are also abusers of alcohol makes the dangers of cocaethylene toxicity a significant health concern.

Sources: Andrews, P. (1997). Cocaethylene toxicity. Journal of Addictive Diseases, 16, 75–84. Harris, D. S.; Everhart, E. T.; Mendelson, J.; and Jones, R. T. (2003). The pharmacology of cocaethylene in humans following cocaine and ethanol administration. Drug and Alcohol Dependence, 72, 169–182.

Where to go for assistance: http://drugabuse.gov/infofacts/cocaine.html

This web site is sponsored by the National Institute of Drug Abuse and contains a comprehensive examination of cocaine risks, including the combination of cocaine with alcohol.

92 ■ Part two Legally restricted Drugs in our Society

Leo XII, to name just a few of Mariani’s fans. Frederic Bartholdi, designer of the Statue of Liberty, wrote in a letter to Mariani that if he had been drinking Vin Mariani while designing the statue, it would have been more than three times taller.6 We can only assume that he meant his remark to be complimentary.

Meanwhile, in the United States, Atlanta pharma- cist John Pemberton was successful in selling an imita- tion form of Vin Mariani that he called French Wine Cola. In 1885, however, as a concession to the Ameri- can temperance movement (see Chapter 8), he took out the alcohol, added carbonated water, and reformu- lated the basic mixture to combine the coca with the syrup of the African kola nut containing about 2 percent caffeine. Coca-Cola was born.

On the strength of the beverage containing both coca and caffeine, early advertisements for Coca-Cola emphasized the drink as a stimulating “brain tonic” that made you feel more productive and as a remedy for such assorted nervous ailments as sick headaches

and melancholia (in the nineteenth-century, the term was used to mean depression).7 The medicinal slant to the early promotion of Coca-Cola is probably the reason why soda fountains began to appear in drugstores.8

A number of competing brands with similar formula- tions soon sprang up, with names such as Care-Cola, Dope Cola, Kola Ade, and Wiseola.9 Eventually, public pressure brought about official restrictions on the patent medicine industry, which, by the beginning of the twentieth century, was marketing more than fifty thousand unregulated prod- ucts.10 The Pure Food and Drug Act of 1906 specified that all active ingredients, including cocaine, had to be listed on patent medicine labels. In Canada, the Proprietary and Patent Medicine Act of 1908 banned cocaine from pat- ent medicines entirely, but in the United States no further restrictions on cocaine sales or use were imposed until the Harrison Act of 1914 (see Chapter 2).

Increasingly aware of a rising tide of public sen- timent against cocaine, the Coca-Cola Company changed the formula in 1903 from regular coca leaves to de-cocainized coca leaves, which eliminated the cocaine itself but retained the coca flavoring that remains to this day (see Drugs . . . in Focus on page 93). The “pause that refreshed” America would henceforth be due only to the presence of sugar and caffeine.

In the meantime, cocaine was becoming a major factor in the practice of medicine. In the United States, William Halsted, one of the most distinguished surgeons of the time and one of the founders of the Johns Hopkins School of Medicine, studied the effect of cocaine in anesthetizing nerves and whole limbs. In the process, he acquired a cocaine habit of his own (which was replaced several years later by dependence on morphine). It was in Europe, however, that the psy- chological implications of cocaine were explored most extensively, ironically through the triumphs and tribula- tions of Sigmund Freud.

Freud and Cocaine In 1884, Freud was a struggling young physician, given to bouts of depression and self-doubt but nonetheless determined to make his mark in the medical world. He had read a report by a German army physician that supplies of pure cocaine helped soldiers endure fatigue and feel better in general. Freud secured some cocaine for himself and found the experience exhilarating; his depression lifted, and he felt a new sense of boundless energy. His friend and colleague Dr. Ernst von Fleischl- Marxow, taking morphine and enduring a painful ill- ness, borrowed some cocaine from Freud and reported favorable results as well.

In the late nineteenth century, the Coca-Cola Company advertised its beverage in medicinal terms. A company let- terhead of this period spoke of Coca-Cola as containing “the tonic properties of the wonderful coca plant.”

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 93

Before long, Freud was distributing cocaine to his friends and his sisters, and he even sent a supply to his fiancée Martha Bernays. In the words of Freud’s biographer Ernest Jones, “From the vantage point of our present knowledge, he was rapidly becoming a public menace.”11 We can gain some perspective on the effect cocaine was having on Freud’s behavior at this time through an excerpt from a personal letter to Martha:

Woe to you, my Princess, when I come. I will kiss you quite red and feed you till you are plump. And if you are forward you shall see who is the stronger, a gentle little girl who doesn’t eat enough or a big wild man who has cocaine in his body [underlined in the original]. In my last severe depression I took coca again and a small dose lifted me to the heights in a wonderful fashion. I am just now busy collect- ing the literature for a song of praise to this magical substance.12

Within four months, his “song of praise” essay, “Über Coca” (“Concerning Coca”), was written and published.

Unfortunately, the sweetness of Freud’s romance w i t h c o c a i n e s o o n t u r n e d s o u r. Fr e u d h i m s e l f escaped becoming dependent on cocaine, although

later in his life he clearly became dependent on nic- otine (see Chapter 10). His friend Fleischl was not so lucky. Within a year, Fleischl had increased his cocaine dose to twenty times the amount Freud had taken and had developed a severe cocaine-induced psychosis in which he experienced hallucinations that snakes were crawling over his skin (an example of a phenomenon now referred to as formication). Fleischl suffered six years of agony and anguish until his death. By 1887, Freud had retracted his earlier stance on the drug.

The story of Freud’s infatuation with cocaine and his later disillusionment with it can be seen as a min- iature version of the modern history of cocaine itself.13 From 1880 to 1910, the public reaction to cocaine went from wild enthusiasm to widespread disapproval. A sim- ilar cycle of attitudes swept the United States and the world a century later.

Drugs . . . in Focus

What Happened to the Coca in Coca-Cola? Every day, in a drab factory building in suburban Maywood, New Jersey, a select team of employees of the Stepan Company carries out a chemical procedure that has been one of the primary responsibilities of the company since 1903. They remove cocaine from high- grade coca leaves. The remainder, technically called “decocainized flavor essence” is then shipped to the Coca-Cola Company as part of the secret recipe for the world’s favorite soft drink.

Each year, the Stepan Company is legally sanctioned by the U.S. government (and carefully monitored by the Drug Enforcement Administration) to receive shipments of about 175,000 kilograms of coca leaves from Peruvian coca farms, separate the cocaine chemically, and produce about 1,750 kilograms of high-quality cocaine. Its annual

output is equivalent to approximately 20 million hits of crack, worth about $200 million if it were to make it to the illicit drug market. Fortunately, the Stepan Company has an impeccable security record.

In case you are wondering what happens to the cocaine after it is removed from the coca leaves, it turns out that Stepan is the official distributor of cocaine to its legitimate market in the world of medicine for use as a local anesthetic.

As a result, the Stepan Company essentially has it both ways. It is the exclusive U.S. supplier of cocaine for use in medical settings, as well as the decocainized coca in your next can of Coke.

Sources: Inciardi, J. A. (2002). The war on drugs III. Boston: Allyn and Bacon, p. 21. Miller, M. W. (1994, October 17). Quality stuff: Firm is peddling cocaine, and deals are legit. Wall Street Journal, pp. A1, A14.

formication: Hallucinatory behavior produced by chronic cocaine or amphetamine abuse, in which the individual feels insects or snakes crawling either over or under the skin.

94 ■ Part two Legally restricted Drugs in our Society

Acute Effects of Cocaine

Although the effects of cocaine on the user vary in degree with the route of administration, the purity of the dose, and the user’s expectations about the experience, certain features remain the same. The most prominent reaction is a powerful burst of energy. If the cocaine is injected intravenously or smoked, the extremely intense effect (often referred to as a “rush” or “high”) is felt within a matter of seconds and lasts only five to ten min- utes. If the drug is snorted through the nose, the effect is less intense than when injected or smoked but lasts somewhat longer, approximately 15 to 30 minutes.

Users also experience a general sense of well-being, although in some instances cocaine may precipitate a panic attack.14 As levels of cocaine diminish, the mood changes dramatically. The user becomes irrita- ble, despondent, and depressed. These aftereffects are uncomfortable enough to produce a powerful craving for another dose.

Cocaine’s effect on sexual arousal is often cited as the basis for its purported allure as an aphrodisiac. On the one hand, interviews of cocaine users frequently include reports of spontaneous and prolonged erections in males and multiple orgasms in females during initial doses of the drug. On the other hand, cocaine’s reputa- tion for increasing sexual performance (recall Freud’s reference in his letter to Martha) may bias users toward a strong expectation that there will be a sexually stim- ulating reaction, when in reality the effect is a much weaker one. As one cocaine abuser expressed it, “Every- body says that it’s an aphrodisiac. Again, I think some people say it because it’s supposed to be. I think that it’s just peer group identification. . . . I never felt that way. I was more content to sit there and enjoy it.”15 The fact is that chronic cocaine use results in decreased sexual performance and a loss of sexual desire, as the drug essentially takes the place of sex.

Cocaine produces a sudden elevation in the sym- pathetic branch of the autonomic nervous system (see Chapter 3). Heart rate and respiration are increased, while appetite is diminished. Blood vessels constrict, pupils in the eyes dilate, and blood pressure rises. The cocaine user may start to sweat and appear suddenly pale. The powerful sympathetic changes can lead to a cerebral hemorrhage or heart failure. Cardiac arrhyth- mia results from cocaine’s tendency to bind to heart tissue itself. While adverse cardiovascular effects are the most significant medical consequences of cocaine use, adverse effects have been observed in practically every organ in the body. As you may recall from Chap- ter 2, cocaine is the drug most often involved in drug- related hospital emergency department visits and one of the drugs most frequently involved in drug-related deaths.16

The extreme effects of cocaine on bodily organs, particularly the heart, stem from its ability not only to excite the sympathetic system but to inhibit the para- sympathetic system as well (Health Alert). Given the high level of sympathetic arousal, it is not surprising that motor skills are adversely affected. In a study of drivers showing reckless behavior on the road, those found to have been under the influence of cocaine were wildly overconfident in their abilities, taking turns too fast or

Quick Concept Check 4.1

Understanding the History of Cocaine Check your understanding of the history of cocaine by matching the names on the left with the identifications on the right. Be careful; some identifications may not match up with any of the names.

1. Angelo Mariani

2. John Pemberton

3. William Halsted

4. Sigmund Freud

5. Ernst von Fleischl- Marxow

a. Friend of Sigmund Freud; first documented case of cocaine psychosis

b. Developer of Coca-Cola, originally containing cocaine

c. Early advocate of restricting cocaine use in the United States

d. Cofounder of Johns Hopkins Medical School; early developer of cocaine to anesthetize nerves and whole limbs

e. A popular figure in present- day Peru

f. Early advocate of cocaine use; originator of psychoanalysis

g. Promoter of a popular coca-laced wine

Answers: 1. g 2. b 3. d 4. f 5. a

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 95

weaving through traffic. One highway patrol officer called this behavior “diagonal driving. They were just as involved in changing lanes as in going forward.” Yet they would pass the standard sobriety tests (such as walk- ing a straight line) that are designed to detect alcohol intoxication.17

Chronic Effects of Cocaine

Repeated and continued use of cocaine produces undesirable mood changes that can be alleviated only when the person is under the acute effects of the drug. Chronic cocaine abusers are often irrita- ble, depressed, and paranoid. As was true in Fleischl’s experience with cocaine, long-term abuse can pro- duce the disturbing hallucinatory experience of f o r m i c a t i o n . T h e s e n s a t i o n o f “ c o c a i n e b u g s ”

crawling on or under the skin can become so severe that abusers may scratch the skin into open sores or even pierce themselves with a knife to cut out the imaginary creatures. These hallucinations, together with feelings of anxiety and paranoia, make up a serious mental disorder referred to as cocaine psychosis.

When snorted, cocaine causes bronchial mus- cles to relax and nasal blood vessels to constrict; the opposite effects occur when the drug wears off. As the bronchial muscles contract and nasal blood ves- sels relax, chronic abusers endure continuously stuffy or runny noses and bleeding of nasal membranes. In advanced cases of this problem, the septum of the nose can develop lesions or become perforated with small holes, both of which present serious problems for breathing.

A Time magazine cover story (July 6, 1981) depicted cocaine in a manner that was long on “status” and short on “menace.” It described the social phenomenon in this way: “In part precisely because it is such an emblem of wealth and status, coke is the drug of choice for perhaps millions of solid, conventional and often upwardly mobile citizens—lawyers, businessmen, students, government bureaucrats, politicians, policemen, secretaries, bankers, mechanics, real estate brokers, and waitresses.”

H e A l t H A l e r t !

the Physical Signs of Possible Cocaine Abuse • Dilated (enlarged) pupils • Increased heart rate • Increased irritability • Paranoia • Sneezing and irritability in the nose (if cocaine has

been snorted) • Feelings of depression • Insomnia • Decreased appetite and significant weight loss

Where to go for assistance: www.cocaine.org/cokalc.htm

A variety of informative articles can be found on cocaine abuse and combinations with other drugs through this web site.

cocaine psychosis: A set of symptoms, including hallucinations, paranoia, and disordered thinking, produced by chronic use of cocaine.

96 ■ Part two Legally restricted Drugs in our Society

Medical Uses of Cocaine

When applied topically on the skin, cocaine has the abil- ity to block the transmission of nerve impulses, deaden- ing all sensations from the area. The use of cocaine as an anesthetic for nasal, lacrimal duct (tear duct), and throat surgery remains its only legitimate medical application.18

Even though cocaine is available for use in these situations, other topical anesthetics are typically pre- ferred because they present fewer problems in their use. One disadvantage of cocaine is that it might inad- vertently be absorbed into the bloodstream, leading to an acute cocaine response that is unrelated to the anes- thetic effect. Another problem is that cocaine produces intense vasoconstriction (constriction of blood vessels). This can be helpful in reducing bleeding during a surgi- cal procedure, but the intensity of the vasoconstriction may have undesirable side effects. Finally, the local anesthetic effects are brief because cocaine breaks down so rapidly and requires reapplications to remain effec- tive. Local anesthetics, such as lidocaine (brand name: Xylocaine), have the advantage of being active over a longer period of time and not causing the problems associated with cocaine.

How Cocaine Works in the Brain

Cocaine greatly enhances the activity of dopamine in the brain. The actual effect is to block the reuptake pro- cess at the synapse, so dopamine stimulates the postsyn- aptic receptors longer and to a greater degree. Unlike the amphetamines (discussed later in this chapter), the structure of cocaine does not resemble the structure of dopamine, so why cocaine should block its reuptake so effectively is not at all clear. Nonetheless, what has been determined is that the acute effect of euphoria experienced through cocaine is directly related to an increase in dopamine activity in the region of the brain that controls pleasure and reinforcement in general: the nucleus accumbens (see Chapter 3). The current scien- tific thinking is that this alteration in brain chemistry has a profound effect on an individual’s decision-making skills and an individual’s potential for developing a depen- dence on cocaine (or some other drug of abuse).

Chronic cocaine abuse, however, leads to the loss of about 20 percent of the dopamine receptors in this region of the brain over time. The depletion of dopa- mine receptors among long-term cocaine abusers has been observed up to four months after the last cocaine exposure, even though the cocaine abuser no longer

has cocaine in his or her system. As a result, there is a tendency toward a decline in the experience of pleasure from natural reinforcers. In fact, cocaine abusers fre- quently report that their craving for cocaine no longer stems from the pleasure they felt when taking it initially. Their lives may be in a shambles, and the acute effects of euphoria from cocaine may no longer be strong, but they still crave the drug more than ever. In other words, there is now a disconnection between “liking” and “wanting.”19

One feature of cocaine is quite unlike that of other psychoactive drugs. Although cocaine abusers, over repeated cocaine exposures, develop a pattern of drug tolerance to its euphoric effect, they develop a pattern of sensitization (a heightened responsiveness) with respect to motor behavior and brain excitation. This phenom- enon, referred to as the kindling effect, makes cocaine particularly dangerous because cocaine has the poten- tial for setting off brain seizures. Repeated exposure to cocaine can lower the threshold for seizures, through a sensitization of neurons in the limbic system over time. As a result of the kindling effect, deaths from cocaine overdose may occur from relatively low dose levels.20

Present-Day Cocaine Abuse

The difficult problems of cocaine abuse in the United States and around the world mushroomed during the early 1970s and continue to the present day, although the incidence of abuse is down from peak levels reached around 1986. In ways that resembled the brief period of enthusiasm for cocaine in 1884, attitudes during the early period of this “second epidemic” were incred- ibly naive. Fueled by media reports of use among the rich and famous, touted as the “champagne of drugs,” cocaine became synonymous with a life of wealth, glam- our, and sophistication. A Time magazine cover story in 1981 depicted cocaine as long on “status” and short on “menace.” The article concluded there was such a close identification with wealth and social accomplishment that cocaine was considered the drug of choice “. . . for perhaps millions of solid, conventional and often upwardly mobile citizens—lawyers, businessmen, stu- dents, government bureaucrats, politicians, policemen,

kindling effect: A phenomenon in the brain that produces a heightened sensitivity to repeated administrations of some drugs, such as cocaine. This heightened sensitivity is the opposite of the phenome non of tolerance.

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 97

secretaries, bankers, mechanics, real estate brokers, and waitresses.”21 At the same time, the medical profession at this time was surprisingly naive about risks of cocaine use. The widely respected Comprehensive Textbook of Psychiatry (1980) stated the following: “If it is used no more than two or three times a week, cocaine creates no serious problem. . . . At present chronic cocaine use does not usually present a medical problem.”22

These attitudes changed dramatically as events in the 1980s unfolded. The death of actor-comedian John Belushi in 1982, followed by the drug-related deaths of other entertainers and sport figures (see Drugs . . . in Focus, page 32) produced a reversal of opinion about the safety and desirability of cocaine. The greatest influence, how- ever, was the arrival of crack cocaine on the drug scene in 1985, which will be examined in the next sections.

From Coca to Cocaine To understand the full picture of present-day cocaine abuse, it is necessary to examine the various forms that cocaine can take, beginning with the extraction of cocaine from the coca plant itself (Figure 4.1). During

the initial extraction process, coca leaves are soaked in various chemical solvents so that cocaine can be drawn out of the plant material. Leaves are then crushed, and alcohol is percolated through them to remove extrane- ous matter. After sequential washings and a treatment with kerosene, the yield is cocaine that is approximately 60 percent pure. This coca paste is, as mentioned ear- lier, combined with tobacco and smoked in many South American countries.

Cocaine in this form, however, is not water-soluble and therefore cannot be injected into the bloodstream. An additional step of treatment with oxidizing agents and acids is required to produce a water-soluble drug. The result is a white crystalline powder called cocaine hydrochloride, about 99 percent pure cocaine and clas- sified chemically as a salt. When in the form of cocaine hydrochloride, the drug can be injected intravenously or snorted. The amount injected at one time is about 16 mg. Intravenous cocaine also can be combined with heroin in a highly dangerous mixture called a speedball.

If cocaine is snorted, the user generally has the option of two methods. In one method, a tiny spoonful of cocaine is carried to one nostril while the other nos- tril is shut, and the drug is taken with a rapid inhalation. In the other method, cocaine is spread out on a highly polished surface (often a mirror) and arranged with a razor blade in several lines, each containing from 20 to 30 mg. The cocaine is then inhaled into one nostril by means of a straw or rolled piece of paper. During the early 1980s, a $100 bill was a fashionable choice (see photo on page 95), drawing attention to the level of income necessary to use cocaine in the first place.23

From Cocaine to Crack Options for using cocaine widened with the develop- ment of free-base cocaine during the 1970s and crack cocaine (or simply crack) during the mid-1980s. In free-base cocaine, the hydrochloride is removed from the salt form of cocaine, thus liberating it as a free base. The aim is to obtain a smokable form of cocaine, which, by entering the brain more quickly, produces a more intense effect. The technique for producing free-base cocaine, however, is extremely hazardous, as it is nec- essary to treat cocaine powder with highly flammable

cocaine hydrochloride: The form of cocaine that is inhaled (snorted) or injected into the bloodstream.

free-base cocaine: A smokable form of cocaine.

crack cocaine or crack: A smokable form of cocaine.

F i g u r e 4 . 1

Steps in producing various forms of cocaine from raw coca.

Coca

Coca paste moderate concentration

Cocaine hydrochloride

high concentration (snorted, i.v. injected)

Free base

high concentration (smoked)

Crack

high concentration (smoked)

chemical extraction

chewed leaves low concentration

“complicated” reverse extraction

“easy” reverse extraction

98 ■ Part two Legally restricted Drugs in our Society

agents, such as ether. If the free base still contains some ether residue, igniting the drug will cause it to explode into flames.

Crack cocaine is the result of a cheaper and safer chemical method, but the result is essentially the same: a smokable form of cocaine. Treatment with baking soda yields small rocks, which can then be smoked in a small pipe. A cracking noise accompanies the burning, hence the name “crack.”

How dangerous is crack? There is no question that the effect of cocaine when smoked exceeds the effect of cocaine when snorted; for some users, it even exceeds the effect of cocaine when injected. Inhaling high- potency cocaine (the purity of cocaine in crack averages about 75 percent) into the lungs, and almost immedi- ately into the brain, sets the stage for a pattern of psy- chological dependence. And at a price of $5 to $10 per dose, cocaine is no longer out of financial reach. The answer is that crack is very dangerous indeed.

At its height of popularity in metropolitan regions of America, crack cocaine had major societal impact on communities where prevalence rates were high. As discussed in Chapter 2, the enormous monetary prof- its from the selling of crack caused inner-city crime and violence to skyrocket (Figure 4.2). Women who were crack abusers found that their drug cravings over- whelmed their maternal instincts, resulting in their neglecting the basic needs of their children, either in postnatal or prenatal stages of life. In New York, for example, the number of reported cases of child abuse and neglect increased from 36,000 in 1985 to 59,000 in 1989, a change largely attributed to the introduction of crack. Alarming reports of adverse effects on children born to crack-abusing mothers abounded, though initial concerns have been largely discounted in the light of subsequent data (see Drugs . . . in Focus).24

Public demonstrations in urban communities in the 1980s and 1990s were one way of responding to the desolation and misery resulting from crack cocaine abuse.

F i g u r e 4 . 2

From coca farm prices in Peru to street prices as crack cocaine. The value increases by approximately 8600 percent, from as little as $300 to as much as $26,000 for the 400 pounds of coca required to produce the one pound of cocaine and eventually the equiva- lent amount of crack.

Source: Information courtesy of the Drug Enforcement Administra- tion, U.S. Department of Justice, Washington, DC.

$300 to $700: Payment to Peruvian farmers for the 400 pounds of coca leaves necessary to produce one pound of cocaine

$1,500 to $2,000: Value of one pound of re�ned cocaine when it leaves Colombia for Mexico

$10,000 to $26,000: Street price of small doses of crack cocaine when bought in major American cities

Shipments of cocaine from Colombia are transported through Mexico and broken down into smaller units for smuggling across the U.S. border. After crossing the border, cocaine is reconsolidated and driven to distribution points for manufacture into street doses of crack cocaine.

1 2 3

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 99

Although crack abuse remains a problem, the num- ber of new crack abusers has declined substantially, par- ticularly in the inner-city communities of the United States. In 1998, whereas 36 percent of all males over thirty-six years old who were arrested in New York had

used crack, little more than 4 percent of those fifteen to twenty years old had done so. A principal reason for this change has been the current stigmatized image of the “crack head,” considered a social loser in his or her community.25

Drugs . . . in Focus

Crack Babies Reevaluated: What Really Are the Effects? In the late 1980s, at the height of the crack abuse explo- sion, one particularly alarming possibility posed by public health officials focused on the children of women who had been crack abusers during their pregnancies (the newborns subjected to this abuse are frequently referred to as “crack babies”). Might these innocents incur long-term mental and physical deficits later in life as a result of in utero expo- sure to cocaine? The early signs were not promising. These newborns had lower birth weights and smaller head cir- cumferences, and they displayed tremors, excessive crying, disturbed sleep patterns, and diminished responsiveness, all of which are abnormalities typical of cocaine exposure. The question remained whether there would be deficits in so- cial skills and mental ability when these infants grew older.

Unfortunately there is no simple answer. The main difficulty is the fact that most of the mothers who were cocaine abusers during their pregnancies were more accu- rately polydrug abusers; they typically abused alcohol, mar- ijuana, and tobacco as well as cocaine. Studies comparing cocaine-exposed and non-cocaine-exposed children, there- fore, must control for prenatal exposure to other drugs, gestational age and size at birth, ethnicity, and gender, as well as other factors such as the socioeconomic status and intelligence level of the mother. When these factors are taken into account, some differences in cognitive func- tioning remain and appear to continue being observed as these children progress through their education. The differences that are observed, however, are relatively small, and the contribution of the other possible factors to these differences are typically greater than the contribution of prenatal cocaine exposure alone. In general, boys seem to be more affected by prenatal cocaine exposure than girls.

The consensus among health professionals, therefore, is that developmental difficulties of children as they

progress through childhood and adolescence can be the result of many risk factors (see Chapter 1), including inad- equate prenatal care, poor nutrition, poor parenting, pov- erty, and exposure to stressors in everyday living, as well as exposure to licit drugs such as alcohol and nicotine. Cocaine exposure itself prior to their birth has an adverse effect, but apparently not a unique one.

Why the unusually intense interest in the effects of in utero exposure to cocaine, when the evidence is so much stronger with respect to the more widely available licit drugs, alcohol (Chapter 9) and nicotine (Chapter 10)? As expressed in an editorial in the Journal of the American Medical Association in 2001, a case can be made that the issues in the late 1980s and 1990s extended beyond concerns about public health. To those who viewed drug users in general, and pregnant drug users in particular, with reprehension and distain, the “crack baby” was a symbol. From their perspective, women exposing their unborn children to cocaine were individuals who were selfish enough to cause irreparable damage to an innocent unborn child for the sake of getting high. This image, promoted by the mass media, made it easier to argue for a simplistic, punitive response to the complex causes of drug use.

Sources: Bennett, D. S.; Bendersky, M.; and Lewis, M. I. (2008). Children’s cognitive ability from 4 to 9 years old as a function of prenatal cocaine exposure, environmental risk, and maternal verbal intelligences. Developmental Psychology, 44, 919–928. Chavkin, W. (2001, March 28). Cocaine and pregnancy—time to look at the evidence. Journal of the American Medical Association, 285, 1626– 1628. Lumeng, J. C.; Cabral, H. J.; Cannon, K.; Heeren, T.; and Frank, D. A. (2007). Prenatal exposures to cocaine and alcohol and physical growth patterns to age 8 years. Neurotoxicology and Teratology, 29, 446–457. Oke, S. (2009, January 29). The epidemic that wasn’t. New York Times, p. D1.

100 ■ Part two Legally restricted Drugs in our Society

Patterns of Cocaine Abuse

In 2011, the National Survey on Drug Use and Health estimated that approximately 37 million Americans aged 12 or older had used cocaine at some time in their lives, 3.9 million had used it during the past year, and 1.4 million had used it during the past month. Approxi- mately 8.2 million Americans had used crack at some time in their lives, 625,000 had used it during the past year, and 228,000 had used it during the past month. The past-month prevalence rates for cocaine and crack have declined by more than 40 percent and 45 percent, respectively, compared to 2005.26

Although the incidence of cocaine abuse in the United States is substantially lower than it has been in the past, the incidence of medical emergencies associated with cocaine use, as measured through the DAWN statis- tics, remain substantial. In 2011, approximately 505,000 cocaine-related ED visits were reported by metropolitan

hospitals, representing the largest share (40 percent) of all ED visits involving an illicit drug. It is evident, therefore, that the absolute numbers of current cocaine and crack abusers have declined, but the dangers remain the same.27

In the meantime, variations of cocaine continue to emerge. A cheap formulation called paco has created sig- nificant social problems in Argentina and other regions of South America (see Drugs . . . in Focus).

Treatment Programs for Cocaine Abuse

Treating cocaine abuse presents difficulties that are peculiar to the power of cocaine itself. This is the way one treatment expert has put it:

Coming off cocaine is one of the most anguished, depressing experiences. I’ve watched people talk

Drugs . . . in Focus

Paco: A Cheap Form of Cocaine Floods Argentine Slums and Beyond Paco is a shortened name for “pasta de cocaine” (cocaine paste), but it is actually just a chemical by-product that is left over (and usually discarded) when coca is converted to coca paste along the way to being transformed into high-grade cocaine hydrochloride. It is essentially lab trash, but unfortunately it has become the center of a major public health and social problem in the impov- erished neighborhoods of Buenos Aires and other met- ropolitan ghettos in Argentina—a problem comparable, according to public health officials, to the epidemic of crack cocaine in American cities during the 1980s.

Like crack, paco is smoked so that psychoactive effects are felt within seconds (Chapter 3). In addition, even by the standards of the Argentine poor, paco is extraordinarily cheap. One dose costing the equivalent of about thirty cents produces a powerful high that lasts for two minutes or so. Abusers frequently smoke twenty to fifty (some up to 100) paco cigarettes, or as many as they can afford, during an average day. Its toxicity is augmented by paco

contaminants such as solvents and chemicals like kero- sene and rat poison. Paco dependence is rampant.

Paco abusers are referred to as muertos vivientes (“the undead”). They will sell anything they have or can get their hands on to buy paco. Attempts to control the flow of cocaine paste and the availability of paco from neigh- boring Bolivia, where coca is grown, have largely failed. Recently, Brazil has had to contend with the spillover of paco abuse from Argentina, while becoming a prime customer for cocaine itself. Presently, Brazil is the sec- ond largest consumer of cocaine in the world, after the United States.

Sources: Bale, A. (2011, February 21). Paco: Drug epi- demic sweeping the streets of Argentina. The Argentina Independent. Accessed through http://argentinain dependent.com. Barrionuevo, A. (2008, February 23). Cheap cocaine floods a slum in Argentina, devouring lives. New York Times, pp. A1, A6. Hearn, K. (2006, April 5). Abuse of the highly addictive cocaine by-product “paco” is causing officials to revamp drug laws. Christian Science Monitor, p. 4. Ryzik, M. (2007, June 10). Cocaine: Hidden in plain sight. New York Times, Section 9, pp. 1, 9.

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 101

about coming off freebase, and one of the things I noticed was the nonverbal maneuvers they use to describe it. It looks like they’re describing a heart attack. They have fists clenched to the chest. You can see that it hurts. They can re-create that hurt for you because it’s a devastating event. They’ll do almost anything to keep from crashing on cocaine. And on top of that, they’ll do just about anything to keep their supply coming. Post-cocaine anguish is a strong inducement to use again—to keep the pain away.28

The varieties of treatment for cocaine abuse all have certain features in common. The initial phase is detoxification and total abstinence: The cocaine abuser aims to achieve total withdrawal with the least pos- sibility of physical injury and minimal psychological discomfort. During the first twenty-four to forty-eight hours, the chances are high that there will be profound

depression, severe headaches, irritability, and distur- bances in sleep.29

In severe cases involving a pattern of compulsive use that cannot be easily broken, the cocaine abuser needs to be admitted for inpatient treatment in a hos- pital facility. The most intensive interventions, medi- cal supervision with psychological counseling, can be made in this kind of environment. The early stages of withdrawal are clearly the most difficult, and the recovering abuser can benefit from around-the-clock attention that only a hospital staff can give.

The alternative approach is an outpatient program, under which the individual remains at home but trav- els regularly to a facility for treatment. An outpatient program is clearly a less expensive route to take, but it works only for those who recognize the destruc- tive impact of cocaine dependence on their lives and enter treatment with a sincere desire to do whatever is needed to stop.30

P o r t r A i t Robert Downey Jr. and Others—Cleaning Up after Cocaine

Since 2008, we have known Robert Downey Jr. through an astounding run of professional success. Through his blockbuster movies—Iron Man, in 2008, Sher- lock Holmes in 2009, Iron Man 2 in 2010, Sherlock Holmes: A Game of Shadows in 2011, Ironman 3 in 2013—Downey essentially “owns” two Hollywood franchises that have no end in sight (see photo on the right).

It is easy to forget the way that Downey’s life was going in the 1990s. In 1999, Downey had spent a year in prison after being convicted on charges of cocaine possession. Upon his release, he was featured on the successful Ally McBeal TV show, only to be fired in 2000. His drug-abuse problems had first begun making headlines in 1996, when he was found with cocaine, heroin, and a pistol in his car. By January 2003, Downey, at the age of thirty-seven, could re- mark that he was “a little older” and “mildly wiser” at the premiere of a new film, his first since he had com- pleted a yearlong court-ordered drug

rehabilitation program in 2002. At the time, he was about one year into a three-year probation period, after pleading no-contest to cocaine posses- sion and being under the influence during a November 2000 arrest in a Palm Springs hotel (see photo on the left).

Downey’s self-destructive lifestyle appears to be behind him, a tribute to successful substance abuse treatment. Yet, like any recovering substance abuser, he acknowledges the fragility of his current life:

I don’t understand that somehow everything was going to turn out O.K. from this lousy, exotic, and dark triple chapter of my life. . . . I don’t think I will ever go that fast again.

There are well-known casualties of the struggle over cocaine abuse— River Phoenix in 1993, Chris Farley in 1998, and Mitch Hedberg in 2005,

all of them having died from a lethal combination of cocaine and heroin. Fortunately, however, Downey is not alone in his continuing recovery over substance abuse. Actors and actresses (Drew Barrymore, Samuel L. Jackson, Michael Douglas, Kelsey Grammer) and musicians (Eric Clapton, Steven Tyler, David Bowie) are among many celebrities who have gone from bad times to good, whether their sub- stance of abuse was cocaine or heroin or alcohol or some combination of all three. Chapter 17 will deal with the issues of substance abuse treatment and the important role that treatment programs play in the lives of people at all levels of society.

Sources: Carr, D. (2008, April 20). Been up, been down. Now? Super. New York Times, pp. 1, 13. Quotation on page 13. Downey’s back, older and “mildly wiser” (2003, January 21). Kidd, C. (2009, February 8). Robert Downey, Jr. New York Times, p. MM45. Lemonick, M.D. (2000, December 11). Downey’s downfall. Time, p. 97.

102 ■ Part two Legally restricted Drugs in our Society

For cocaine abusers who have failed in previous attempts in outpatient treatment or for those who are in denial of their cocaine dependence, an inpatient approach may be the only answer. For most abusers, long after they have apparently “kicked the habit,” it is important to stay away from places where cocaine and other drugs are prevalent, and to stay away from former friends and other stimuli that can act as environmen- tal triggers to resume drug-taking behavior. You may recall that these precautions are crucial, given the power of conditioned environmental cues (Chapter 2) for relapse.31 A prominent psychiatrist has expressed the phenomenon as a “kind of pathologic learning [that] lies at the heart of compulsive drug use. . . . the individual is vulnerable in these deeply encoded asso- ciations that can set off a craving, seemingly out of the blue.”32

A third alternative is a combined approach in which a shortened inpatient program of seven to four- teen days is followed by an intensive outpatient program that continues for several months.

Whether on an inpatient or an outpatient basis, there are several approaches for treatment. One alternative is the self-help support group Cocaine Anonymous, modeled after the famous twelve-step Alcoholics Anonymous program (see Chapter 9). In this program, recovering cocaine abusers meet in group sessions, learn from the life experiences of other members, and gain a sense of accomplishment from remaining drug-free in an atmosphere of fellowship

and mutual support. In another drug-treatment option, cocaine abusers meet with cognitive-behavioral thera- pists, who teach them new ways of acting and thinking in response to their environment. During the course of cognitive-behavioral therapy, cocaine abusers are urged to avoid situations that lead to drug use, recog- nize and change irrational thoughts, manage negative moods, and practice drug-refusal skills. While the suc- cess rates of both approaches are approximately the same for patients in cocaine-abuse treatment over- all, some evidence suggests that a cocaine abuser’s personal characteristics may affect the kind of treat- ment that will work best (Figure 4.3). Whatever the approach taken, however, it is clear that an intensive relearning process has to go on, because many long- term cocaine abusers cannot remember a life without cocaine.33

Today, pharmacological approaches in cocaine- abuse treatment, as well as the combination of phar- macological and behavioral approaches, are being vigorously pursued. A promising example of a purely pharmacological strategy is development of the com- pound gamma vinyl-GABA (vigabatrin), currently FDA- approved for the treatment of epilepsy. Essentially, it has been established that vigabatrin “short-circuits” the reinforcing effect of cocaine by preventing the sudden surge of dopamine in the brain when cocaine is admin- istered. Animals that have become cocaine-dependent no longer self-administer cocaine after taking vigabatrin and are no longer attracted to locations that have been

Cognitive- Behavioral

Therapy

12-Step Cocaine

Anonymous Program

50% 25%

18% 48%

35% 40%

46% 54%

Patients with high abstract reasoning

Patients with low abstract reasoning

Patients with high religious beliefs

All patients

F i g u r e 4 . 3

Percentage of patients achieving four consecutive weeks of cocaine abstinence, comparing two types of treatment.

Source: Adapted from Shine, B. (2000, March). Some cocaine abusers fare better with cognitive- behavioral therapy, others with 12-step programs. NIDA Notes, 15 (1), 9.

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 103

associated with cocaine in the past, implying that ani- mals are not better able to resist the conditioned cues for chronic cocaine use. In 2009, randomized double- blind, placebo-controlled trials involving a sample of long-time cocaine abusers showed that fourteen out of fifty (28%) of abusers treated with vigabatrin showed negative urine tests for cocaine lasting for nine weeks, whereas only 4 out of fifty three (7.5%) treated with a placebo did so. Twelve subjects in the vigabatrin group and two subjects in the placebo group remained absti- nent for thirteen weeks, the full-length of the study. Interestingly, among subject reporting prior alcohol use, 44 percent in the vigabatrin group reported abstinence from alcohol, compared to six percent in the placebo group.34

The potential for relapse is particularly challenging among recovering cocaine abusers, primarily as a result of powerful conditioned cues that have been associ- ated with the drug. A specialist in cocaine abuse reha- bilitation tells this story: “A woman was doing well in treatment. Then one day she was changing her baby’s diaper. She used baby powder and the sight of the white powder induced a tremendous craving for cocaine.”35 The continuing investigation of treatment and preven- tion approaches to cocaine abuse, emphasizing the drug craving factor, reflects a general orientation toward reducing the negative impact of drug-taking behavior on the individual and society (the “demand” side), as opposed to reducing the availability of the drugs them- selves (the “supply” side).

Amphetamines

One of humanity’s fondest dreams is to have the power of unlimited endurance, to be able to banish fatigue from our lives, to be fueled by endless energy as though we had discovered some internal perpetual-motion machine. We all have wanted, at some time in our lives, to be a super-hero. Cocaine, as we know, gives us that illusion. The remainder of this chapter will exam- ine another powerful drug source for these feelings of invincibility: amphetamines. As we will see, the attrac- tions and problems of abuse associated with cocaine and amphetamines are quite similar.

The Different Forms of Amphetamines To understand amphetamine abuse, both past and present, it is necessary to know something about the molecular structure of amphetamines themselves.

Amphetamine can be represented chiefly as a specific arrangement of carbon (C), hydrogen (H), and nitrogen (N) atoms (Figure 4.4, shown above), either in a “right- handed” version or a “left-handed” version (mirror image). The more potent version is the right-handed form, called dextroamphetamine or d-amphetamine (brand name: Dexedrine). It is stronger than the left-handed form, called levoamphetamine or l-amphetamine, which is not commonly available by itself. It is, however, com- bined with d-amphetamine in the medication Adderall.

A modified form of d-amphetamine, formulated by substituting CH3 (called a methyl group) for H at one end, is called methamphetamine. This slight change in the formula allows for a quicker passage across the blood–brain barrier. Methamphetamine, often called meth, speed, or crank, has been the primary form of amphetamine abused in recent years.

d-amphetamine: Shortened name for dextroamphet- amine, a potent form of amphetamine marketed under the brand name Dexedrine.

methamphetamine: A type of amphetamine once marketed under the brand name Methedrine. Meth- amphetamine abusers refer to it as meth, speed, or crank.

F i g u r e 4 . 4

The molecular structure of dextroamphetamine, metham- phetamine, dopamine, and norepinephrine. Notice the chemical similarities.

Dextroamphetamine

Methamphetamine

Dopamine

Norepinephrine

C C——

C

C C H C H

CH3 C HC

—— —

— — — — —

—

—

H

H

N ——

C C——

C

C C H C H

CH3 C HC

—— —

— — — — —

—

—

H

CH3

N ——

HO

HO

C C——

C

C C H C H

H C HC

—— —

—— — — — —

—

—

—

H

H

N ——

HO

HO

C C——

C

C C OH C H

H C HC

—— —

—— — — — —

—

—

—

H

H

N ——

104 ■ Part two Legally restricted Drugs in our Society

The History of Amphetamines The origin of modern amphetamines dates back almost five thousand years to a Chinese medicinal herb called ma huang (Ephedra vulgaris) that was used to clear bronchial passageways during bouts of asthma and other forms of respiratory distress. According to Chinese leg- end, this herb was first identified by the Emperor Shen Nung, who also is credited with the discovery of tea and marijuana.

German chemists isolated the active ingredient of ma huang in 1887, naming it ephedrine. It was soon obvious that ephedrine mimicked the stimulation of the sympathetic nervous system in general. In 1932, the pharmaceutical company Smith, Kline and French Laboratories marketed a synthetic form of ephedrine called amphetamine under the brand name Benze- drine as a nonprescription CNS stimulant appetite sup- pressant and bronchial dilator.

During World War II, both U.S. and German troops were given amphetamine to keep them awake and alert. Japanese kamikaze pilots were on amphet- amine during their suicide missions. The advantages over cocaine, the other stimulant drug available at the time, were twofold: Amphetamine was easily absorbed into the nervous system from the gastrointestinal tract, so it could be taken orally; and its effects were much longer-lasting. After the war, amphetamine use was adapted for peacetime purposes. Amphetamine, often referred to as bennies, was a way for college students to stay awake to study for exams and for long-distance truck drivers to fight fatigue on the road. In the meantime, the word got around that amphetamine produced eupho- ria as well, and soon amphetamine became popular for recreational purposes. People found ways of opening up the nonprescription amphetamine inhalers, with- drawing the contents, and getting high by drinking it or injecting it intravenously. Since each inhaler contained 250 mg of amphetamine, there was enough for sev- eral powerful doses. During the early 1960s, injectable amphetamines could be bought with forged prescrip- tions or even by telephoning a pharmacy and posing as a physician. By 1965, amendments to federal drug laws tightened the supply of prescription amphetamines, requiring manufacturers, wholesalers, and pharmacies to keep careful records of amphetamine transactions, but amphetamines soon became available from illegal laboratories.36

Amphetamine abuse in the United States reached a peak around 1967, declining slowly over the 1970s as other drugs of abuse, notably cocaine, grew in popular- ity. By 1970, 10 percent of the U.S. population over

fourteen years of age had used amphetamine, and more than 8 percent of all drug prescriptions were for amphet- amine in some form.37 For about two decades afterward, amphetamine abuse steadily faded from prominence in the drug scene. Cocaine and later crack cocaine became the dominant illicit stimulants of abuse. Only since the mid-1990s has amphetamine abuse, in the form of methamphetamine abuse, resurfaced as a sig- nificant social concern.

How Amphetamines Work in the Brain We can get a good idea of how amphetamines work in the brain by looking carefully at the molecular structures of dopamine and norepinephrine alongside d-amphet- amine and methamphetamine in Figure 4.4. Note that there are only slight differences among them. Because of the close resemblance to dopamine and norepineph- rine, it is not hard to imagine amphetamines increas- ing the activity level of these two neurotransmitters. Specifically, amphetamines cause increased amounts of dopamine and norepinephrine to be released from synaptic knobs and also slow down their reuptake from receptor sites. As described in Chapter 3, dopamine fig- ures prominently in regions of the brain (notably the nucleus accumbens) associated with positive reinforce- ment. The euphoric effects of amphetamines, and the craving for them during abstinence, are considered to result from changes in dopamine activity. In this sense, amphetamines and cocaine share a common neuro- chemical mechanism.

Acute Effects of Amphetamines

The acute behavioral effects of amphetamine, in either d-amphetamine or methamphetamine form, closely resemble those of cocaine, and the adverse medical consequences are similar as well. However, amphet- amine effects extend over a longer period of time. For intervals of eight to twenty-four hours, there are signs of increased sympathetic autonomic activity, such as faster breathing and heart rate as well as hyperthermia (increased body temperature) and elevated blood pres- sure. Users experience feelings of euphoria and invin- cibility, decreased appetite, and an extraordinary boost in alertness and energy. Adverse and potentially lethal

amphetamine (am-FeH-ta-meen): A family of ephedrine-based stimulant drugs.

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 105

bodily changes include convulsions, chest pains, and stroke. In 2011, approximately 103,000 of drug-related ED visits in the United States were attributable spe- cifically to methamphetamine abuse, accounting for about two-thirds of visits related to stimulant abuse in general.38

Chronic Effects of Amphetamines

The chronic effects of amphetamine abuse are both bizarre and unpleasant, particularly in the case of methamphetamine. Heavy methamphetamine abusers may experience formication hallucinations similar to those endured by cocaine abusers. They may become obsessed with the delusion that parasites or insects have lodged in their skin and so attempt to scratch, cut, or burn their skin in an effort to remove them. It is also likely that they will engage in compulsive or repetitive behaviors that are fixated upon ordinarily trivial aspects of life; an entire night might be spent, for example, counting the corn flakes in a cereal box. Compulsive jaw movements and teeth grinding can cause significant dental damage over time.39

The most serious societal consequence of metham- phetamine abuse is the appearance of paranoia, wildly bizarre delusions, hallucinations, tendencies toward violence, and intense mood swings. In the words of one health professional, “It’s about the ugliest drug there is.”40 Because the symptoms have been observed with the chronic abuse of amphetamines of any type, they are referred to collectively as amphetamine psychosis. The possibility that methamphetamine abusers may not have slept for three to five days increases their tendency toward extremely irritable, paranoid, and potentially violent behavior. These symptoms, which are called “tweaking” by the drug-abuse community, are displayed by up to 50 percent of methamphetamine abusers and present particular challenges to law-enforcement officers who have to deal with abusers under these circumstances. The close resemblance to paranoid schizophrenia has led to speculation that the two con- ditions may have a common underlying neurochemi- cal basis: an overstimulation of dopamine-releasing

neurons in those regions in the brain that control emo- tional reactivity.41

A study of heavy methamphetamine abusers has shown changes in chemical metabolites in those regions of the brain that are associated with Parkinson’s disease, suggesting that their methamphetamine expo- sure may predispose this group to acquiring Parkinson symptoms later in life. Fortunately, however, recent evidence indicates that chemical changes in the brain in chronic methamphetamine abusers can be at least partially reversed by abstinence from the drug for a year or more.42

Methamphetamine Abuse In the United States, the emergence of widespread methamphetamine abuse was intermingled with the marijuana and LSD scene during San Francisco’s “Summer of Love and Peace” in 1967. Almost from the beginning, however, speed freaks—as methamphet- amine abusers were called—whose behaviors were any- thing but loving or peaceful became the outcasts of that society:

These wild-eyed, manic burnout cases would blither on endlessly, rip off anything not welded in place, then go into fits of erratic and violent behavior. . . . They were shunned by other sorts of drug users, and ended up congregating with the only segment of the population who could stomach their company— other speed freaks.43

In the meantime, prescription amphetamines, widely administered during the 1960s for weight con- trol and as a way to combat drowsiness, resulted in large numbers of abusers from practically every segment of society. Even though d-amphetamine was classified as a Schedule II drug in 1970 and the number of d-amphet- amine prescriptions decreased by 90 percent from 1971 and 1986, the pills were still out there, and people found ways to continue an abuse pattern of drug-taking behavior.

Present-Day Patterns of Methamphetamine Abuse

As crack cocaine became increasingly associated with the urban poor and powder cocaine with upscale affluence in the 1980s, amphetamine abuse declined dramatically. In the 1990s, however, as crack cocaine and powder cocaine abuse began to diminish,

amphetamine psychosis: A set of symptoms, includ- ing hallucinations, paranoia, and disordered thinking, resulting from high doses of amphetamines.

106 ■ Part two Legally restricted Drugs in our Society

methamphetamine abuse reemerged on the drug scene. Once identified with the countercultural 1960s, meth- amphetamine became a major stimulant of abuse in the United States, and its popularity is now concentrated among working-class people rather than among the poor or the affluent.

Administered by snorting, injecting, or smok- ing, methamphetamine became one of the few drugs reported to be as prevalent as, or more prevalent than, other illicit drugs in areas outside America’s inner cit- ies. In 2011, the National Survey on Drug Use and Health estimated that approximately 12 million Ameri- cans aged 12 or older had used methamphetamine at some time in their lives, 1,033,000 had used it during the past year, and 439,000 had used it during the past month.44

In the early 1990s, distribution of methamphet- amine was dominated by organized criminal groups operating out of southern California and Mexico, with trafficking routes extending through several U.S. states, including Arizona, Colorado, Iowa, Missouri, Nebraska, North Dakota, and Texas. As mentioned in Chapter 2, the slang term “crank” harkens back to the days of motorcycle gangs who distributed methamphet- amine, hiding the drug in the crankshaft. By the late 1990s, however, thousands of “homegrown” metham- phetamine laboratories proliferated in small towns and rural areas throughout the nation. They were typically situated in mobile homes, campers, vans, and easily hid- den farm sheds, making their detection by law enforce- ment agencies extremely difficult. Toxic residue from methamphetamine manufacture, approximately five pounds of waste for every pound of methamphetamine produced, seeped into the soil and contaminated rivers and streams. Children suffered from inhaling the toxic fumes emitted during the process of methamphetamine manufacture, from the risks of fire and explosions,

and from abuse and neglect by methamphetamine- dependent parents (see Drugs . . . in Focus).

As a response to the methamphetamine abuse prob- lem, a strenuous effort was made to reduce the availability of common products used to manufacture methamphet- amine. Because liquid anhydrous ammonia, commonly used as a farm fertilizer, is an ingredient in the “metham- phetamine recipe,” fertilizer dealers have installed security systems to protect their supplies from theft. Retail outlets are now required by federal law to limit the sales of numer- ous cold remedies (Sudafed, Tylenol Cold, and others) that contain pseudoephedrine—an essential ingredient in the making of methamphetamine. A number of prod- ucts that have formerly been “over-the-counter” (see Chap- ter 14) are now “behind-the-counter.” Customers cannot buy more than the equivalent of approximately seventy 60-mg pseudoephedrine tablets per day and must provide photo identification upon purchase and sign a logbook recording the transaction. This simple move in Oregon in 2006 succeeded in reducing the number of domestic lab seizures by 95 percent from 2005 to 2009. In general, fed- eral authorities reported a sharp decline in the number of domestic methamphetamine laboratory seizures between 2004 and 2008, but in 2010 the amount of seizures of methamphetamine itself as well as prevalence rates had turned upward again. Methamphetamine from nondo- mestic sources, specifically Mexico, has also increased.45

It should be noted that in recent years, methamphet- amine has become an increasingly problematic club drug in New York, Los Angeles, and other major cities (see Chapter 1). A smokable form of methamphetamine hydro- chloride called ice (also referred to as crystal meth), its

A public-service campaign against meth abuse aims to reach young adults.

ice: A smokable form of methamphetamine hydro- chloride. It is often referred to as crystal meth because of its quartz-like appearance.

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 107

Drugs . . . in Focus

Methamphetamine and the Heartland of America In 2005, the methamphetamine abuse epidemic in Watauga County, North Carolina, had gotten so bad that it has nicknamed itself “the county that never sleeps.” Dozens of methamphetamine laboratories in the region were raided. Every fire emergency was treated as if it were a meth-lab fire.

Watauga County was not alone. A survey of more than 500 county sheriffs in the United States, conducted by the National Association of Counties in 2005, documented the alarming proportions of meth abuse across the country since 2000. Fifty-eight percent of sheriffs in the survey regarded methamphetamine abuse as the biggest drug problem they faced, ahead of concerns about heroin, cocaine, or marijuana. In half of the counties surveyed, one in five current prison inmates had been incarcerated in connection with meth-related crimes. In 17 percent of the counties, more than half of the inmate population had been incarcerated for such crimes. A majority of sheriffs reported that meth use was the major contributing factor to increases in robberies or burglaries, domestic violence, and simple assaults. At the same time, only one in six counties reported having the financial resources to sup- port a meth rehabilitation center or program.

Significant increases were reported in cases in which children needed to be placed out of the home as a result of neglect and abuse by parents who were meth abusers or as a result of a child’s proximity to the hazards of meth labs. More than 69 percent of counties in Minnesota reported an increase in meth-related child placements between 2004 and 2005.

Two exacerbating factors have made it particularly dif- ficult for children who are affected by the meth epidemic.

First, meth abuse has been concentrated largely in rural areas, where social service networks are ill-prepared to handle the increased numbers of foster children. Second, the chances of reunifying families torn apart by meth abuse have been considerably lower than in cases involv- ing other forms of drug abuse because of the high rate of relapse among meth abusers in treatment.

In recent years, the picture of meth abuse in America has changed. Federal reports indicate a decline in the number of meth lab seizures, particularly in western U.S. states most dramatically affected by meth abuse, from about 10,000 in 200 to about 4,500 in 2009. This decline is due primarily to the restrictions on acquiring basic ingredients for meth production. The influx of illegal methamphetamine from Mexico, however, has in- creased. This new drug-trafficking pattern indicates that the number of meth abusers in the United States have not diminished overall (in fact, it has increased), but the availability of the drug has simply shifted from a reliance on domestic laboratories in local communities to foreign sources.

Sources: National Association of Counties (2005, July 5). The meth epidemic in America. Two surveys of U.S. counties: The criminal effect of meth on communi- ties and the impact of meth on children. Washington, DC: National Association of Counties. National Drug Intelligence Center (2011). National Drug Threat Assess- ment 2011. Washington, DC: National Drug Intelligence Center, U.S. Department of Justice, Table B3. Substance Abuse and Mental Health Services Administration (2007, January 26). Methamphetamine use. The NSDUH Report. Rockville, MD: Substance Abuse and Mental Health Services Administration. Zernike, Kate (2005, July 11). A drug scourge creates its own form of orphan. New York Times, pp. A1, A15.

name originating from its quartz-like, chunky crystallized appearance, appeared on the drug scene in Hawaii in the late 1980s, but its abuse did not expand to the mainland to a significant degree until the late 1990s. Unfortunately, the combination of a purity of 98 to 100 percent and a highly efficient delivery route through the lungs produces a high level of potential for dependence and a significant social problem. Another is the association between metham- phetamine abuse and increased high-risk sexual behavior among HIV-positive gay or bisexual men.46

Methamphetamine-Abuse Treatment Even though methamphetamine and cocaine are simi- lar in their stimulant effects and both trigger a major elevation in dopamine levels in the brain, the pattern of drug-taking behavior for each type of drug has its own distinctive character. Methamphetamine abusers typi- cally use the drug throughout their waking day, at two- to four-hour intervals, in a pattern that resembles taking medication. Cocaine abusers typically use the drug in the evening and nighttime rather than during the day,

108 ■ Part two Legally restricted Drugs in our Society

taking it in a continuous (binge-like) fashion until all the cocaine on hand has been exhausted. This latter pattern of drug-taking behavior fits the typical picture of the recreational user.

The duration of response to the two drugs may help to explain the differences in usage. Methamphet- amine effects generally last longer than cocaine effects. Therefore, cocaine abusers need relatively more fre- quent administrations to maintain their “high.” On tests that evaluate different forms of cognitive func- tioning, methamphetamine and cocaine abusers show significant differences in the type of cognitive impair- ment that is produced. Methamphetamine abusers are impaired on tests of perceptual speed or manipulation

of information, effects observed to a lesser extent among cocaine abusers. The greatest difference between the two groups is observed when tests require both speed and the manipulation of information.47

On the other hand, the course of methamphet- amine withdrawal—and amphetamine withdrawal in general—is very similar to the course of events described earlier for cocaine. First there is the “crash” when the abuser feels intense depression, hunger, agitation, and anxiety within one to four hours after the drug-taking behavior has stopped. Withdrawal from amphetamines, during total abstinence from the drug, takes between six and eighteen weeks, during which the intense craving for amphetamine slowly subsides.

As in cocaine-abuse treatment, there are inpatient and outpatient programs for methamphetamine abuse, depending on the circumstances and motivation of the abuser. Self-help groups such as Cocaine Anony- mous can be useful as well, since the symptoms of amphetamine withdrawal and cocaine withdrawal are nearly identical. Methamphetamine abusers represent approximately one in twelve individuals in treatment for substance abuse, but relatively few methamphet- amine abusers attempt treatment, much less succeed in recovery. The reason is that they perceive themselves as remaining in control over their drug use, despite evi- dence to the contrary. As a major government report has expressed it:

This perception is particularly dangerous because the crossover from initial use to loss of control is rapid for meth users, and generally they have lost control long before they can acknowledge it . . . . This attitude of denial makes it difficult to convince meth abusers to enter and stay in treatment.48

O v e r a l l , m e t h a m p h e t a mi n e a b u s e r s f i n d i t extremely difficult to become drug-free, and their relapse rate is one of the highest for any category of illicit or licit drug abuse. In light of acknowledged diffi- culties in methamphetamine-abuse treatment, attention has been understandably focused on the prevention of methamphetamine abuse (Health Line).

Medical Uses for Amphetamines and Similar Stimulant Drugs

Although amphetamines in general continue to present potential problems of abuse, there are approved medical applications for amphetamines and amphetamine-like stimulant drugs in specific circumstances. Stimulant

Quick Concept Check 4.2

Understanding Patterns of Cocaine and Methamphetamine Abuse Check your understanding of cocaine or crack cocaine abuse and methamphetamine abuse by identifying each statement as being (a) true with respect to cocaine or crack cocaine but not methamphetamine, (b) true with respect to methamphetamine but not cocaine or crack cocaine, or (c) true with respect to both cocaine or crack cocaine and methamphetamine.

1. Sigmund Freud was an early advocate of its use. __________________

2. Formication hallucinations can occur. __________________

3. Abuse is reported to be as prevalent as or more preva- lent than that of other illicit drugs in areas outside America’s inner cities. __________________

4. A powerful energizing effect can last up to about 20 to 30 minutes. __________________

5. Patterns of abuse can involve smokable forms of the drug. __________________

6. Accepted use as a local anesthetic for certain types of surgery. __________________

7. Sources for illegal manufacture include ingredients in cold remedies and farm fertilizer. __________________

8. Neurochemical effects include an increase in dopa- mine activity in the brain. __________________

Answers: 1. a 2. c 3. b 4. a 5. c 6. a 7. b 8. c

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 109

drugs are prescribed primarily for elementary-school- age children diagnosed as unable to maintain suffi- cient attention levels and impulse control in school or as behaviorally hyperactive. These symptoms are col- lectively referred to as attention-deficit/hyperactivity disorder (ADHD). When there is no evidence of hyper- activity, the designation is shortened to attention deficit disorder (ADD).

ADHD is the most common psychological disorder among children. It is estimated that 3 to 10 percent of all school-age children meet the criteria for ADHD. The prevalence rate is three times greater, and the symptoms are generally more severe, for boys than for girls. These children have average to above-average intelligence but typically underperform academically. As many as two- thirds of school-age children with ADHD have at least one other psychiatric disorder, including anxiety and depression.49

Despite the public image of ADHD as an exclu- sively childhood phenomenon, longitudinal stud- ies have shown that ADHD symptoms persist from childhood into adolescence in about 75 percent of cases and into adulthood in about 50 percent of cases. As adults, these individuals are ten times more likely to be diagnosed with an antisocial personality disorder, twenty-five times more likely to have been

institutionalized for delinquency, and nine times more likely to serve a prison sentence.50

Stimulant Medications for ADHD Commonly prescribed stimulant medications for the treatment of ADHD include oral administrations of the amphetamine-like drug methylphenidate (brand name: Ritalin), a combination of dextroamphetamine and levoamphetamine (brand name: Adderall), and a com- bination of dextroamphetamine and the amino acid lysine (brand name, Vyvanse).

For decades, Ritalin dominated the market in pre- scriptions written for ADHD. Although a growing num- ber of alternative medications are now available for this purpose, Ritalin remains the most recognizable “brand” with respect to ADHD treatment. In this drug’s original formulation, the rapid onset and short duration of Ritalin requires two administrations during a school day: one at breakfast and another at lunchtime, supervised by a school nurse. In the evening, blood levels of Ritalin

Health Line “Bath Salts” as a New Form of Stimulant Abuse

In the 1970s, a medicinal chemist discovered a new type of stimulant by adding an oxygen atom to a section of the amphetamine molecule, resulting in a new stimulant compound that is more powerful than amphetamine, now known as cathinone. Adding a methyl group to metham- phetamine (meth) created a new stimulant drug called methcathinone that was more powerful still.

These findings were more or less scientific curiosi- ties until 2010, when a family of white-crystal designer drugs appeared on the drug scene, marketed to appear like legal bath products (like Epsom salts) and called “bath salts.” The packaging stated “not for human consump- tion” to avoid prosecution under the Federal Analog Act, a law forbidding the sale of drugs substantially similar to already classified Schedule I drugs. By the first half of 2011, the number of bath salts cases noted by U.S. poison control centers had risen steadily. In the peak month of June 2011, 743 cases, most of them of severe incidences of poisoning, were reported. By the end of the year, the number of poisoning cases had fallen somewhat, but they

continue to be a problem not only for law enforcement but also for health officials concerned with public safety. In 2012, President Obama signed into law the Synthetic Drug Abuse Prevention Act, banning synthetic drugs commonly appearing in bath salts. The law also banned other synthetic drugs related to marijuana, marketed un- der the names “Spice” and “K2” (see Chapter 7). Annual prevalence rates for bath salts in 2012 among secondary students ranged between 0.8% for eighth graders and 1.3% for high school seniors, according to the University of Michigan survey.

Sources: Johnston, L.D.; O’Malley, P.M.; Bachman, J.G.; and Schulenberg, J.E. (2012, December 19). The rise in teen marijuana use stalls, synthetic marijuana use levels, and use of “bath salts” is very low. University of Michigan News Service, Ann Arbor. Roy, V. (2012, August 8). Getting tough on ‘bath salts.’ Newsday, p. A6. Marder, J. Bath salts: The drug that never lets go. http://www.pbs.org/ newshour/multimedia/bath-salts/

attention-deficit/hyperactivity disorder (ADHD): A behavioral disorder characterized by increased motor activity and reduced attention span.

110 ■ Part two Legally restricted Drugs in our Society

decline to levels that permit normal sleep. Adderall has a longer duration of action, making it possible to admin- ister a single dose and avoiding school involvement in treatment. In comparative studies, Ritalin and Adderall have been found to be equivalent in effectiveness.51

New drug treatments for ADHD have become available that are essentially variations of the traditional methylphenidate medication. They include a sus- tained-release formulation (brand name: Concerta), a formulation that produces an initial rapid dose of meth- ylphenidate followed by a second, sustained-release phase (brand name: Metadate), and a chemical varia- tion of methylphenidate that allows for a longer duration of action (brand names: Attenade, Focalin). A methyl- phenidate patch (brand name: Daytrana), designed to release the drug through the skin slowly over a period of nine hours, was approved in 2006.

Stimulant drugs improve behavior and learning ability in 60 to 80 percent of children who are correctly diagnosed with ADD or ADHD. In 1999, a major study examining the effects of medication over a fourteen- month period found that medication was more effective in reducing ADHD symptoms than behavioral treat- ment and nearly as effective as a combined approach of medication and behavioral treatment.52

One side effect of stimulant medications is a sup- pression of height and weight gains during these forma- tive years, reducing growth to about 80 to 90 percent of normal levels. Fortunately, growth spurts during the summer, when children are typically no longer taking medication (referred to as “drug holidays”), usually compensate for this problem. Discontinuance of medi- cation, however, has to be carefully monitored. Symp- toms such as lethargy, lack of motivation, and, in some cases, depression can occur during this time. A more serious concern is the increased risk of cardiovascular disease due to the effects of stimulant drugs. An FDA- mandated “black box” warning now appears on ADHD medications as a guide for patients and physicians.53 Fortunately, the main concern about the possible risk of future drug dependence as a result of stimulant treat- ment has been laid to rest. Childhood and adolescent use of stimulant medication for ADHD is not associated with later substance abuse. In fact, there is a nearly two- fold reduction in the risk of future abuse.54

Until recently, the phenomenon of reducing hyperactivity with methylphenidate and related stimu- lant drugs, rather than increasing it, had been quite puzzling to professionals in this field. It is now known that orally administered methylphenidate and related stimulant drugs produce a relatively slow but steady increase in dopamine activity in the brain. This change

in brain chemistry is hypothesized to have two effects that are beneficial to an individual with ADHD. First, increased dopamine may amplify the effects of envi- ronmental stimulation, while reducing the background firing rates of neurons. Thus, there would be a greater “signal-to-noise” ratio in the brain, analogous to having a stronger radio signal received by a radio that no longer emits a large amount of background static. The behav- ioral effect would be an improvement in attention and decreased distractibility. Symptoms of ADHD may be a result of not having a sufficient “signal-to-noise” ratio in the processing of information for tasks that require concentration and focus. Second, increased dopamine may heighten one’s motivation with regard to a par- ticular task, enhancing the salience and interest in that task and improving performance. An individual might perform better on a task simply because he or she likes doing it. The slow rate of absorption achieved through oral administration (Chapter 3) and the relatively slow action of dopamine release in the brain are two factors that make it possible to avoid an emotional high.55

It is commonly assumed that increased dopamine activity accounts for the reduction in ADHD symptoms, but this may not necessarily be the case. In 2003, a selec- tive norepinephrine reuptake inhibitor, atomoxetine (brand name: Strattera) was approved by the Food and Drug Administration (FDA) for the treatment of ADHD in both children and adults. Since Strattera produces an increase in norepinephrine activity in the brain, it is pos- sible that lowered norepinephrine levels play a role in ADHD as well. Strattera has been marketed as a once- a-day nonstimulant medication that reduces ADHD symptoms by increasing norepinephrine levels— not dopamine levels—in the brain. The full story may be either that both norepinephrine and dopamine are jointly involved in ADHD or that ADHD itself may be two separable disorders, one related to dopamine activ- ity and the other related to norepinephrine activity. According to this hypothesis, the symptoms may overlap to such a degree that it is difficult to distinguish the two disorders on a strictly behavioral basis.

Other Medical Applications Narcolepsy (an unpredictable and uncontrollable urge to fall asleep during the day) is another condition for which stimulant drugs have been applied in treatment. In 1999, modafinil (brand name: Provigil) was approved for treating narcolepsy. The advantage of Provigil over traditional stimulant treatments, such as dextroamphet- amine, is that it does not present problems of abuse and produces fewer adverse side effects. In 2009, the

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 111

University of Michigan survey included, for the first time, a question about the nonmedical use of Provigil among high school seniors. At that time, the reported lifetime prevalence rate was 1.8 percent, and the rate has held steady since then. Evidently, the current mis- use of this drug by adolescents is not a serious problem. Whether greater number of college students have taken to Provigil as a “cognitive enhancer” remains to be determined.56

There are also several amphetamine-like drugs available to the public, some of them on a nonpre- scription basis, for use as nasal decongestants. In most cases, their effectiveness stems from their primary action on the peripheral nervous system rather than on the CNS. Even so, the potential for misuse exists: Some users continue to take these drugs over a long period of time because stopping their use results in unpleasant rebound effects such as nasal stuffiness. This reaction, by the way, is similar to the stuffy nose that is experienced in the chronic administration of cocaine.57

Stimulant Medication and Cognitive Enhancement

In 1996, the Swiss pharmaceutical company Ciba-Geigy sent letters to hundreds of thousands of pharmacies and physicians in the United States, warning them to exert greater control over Ritalin tablets and prescriptions to obtain them. The alert came in response to reports that Ritalin was becoming a drug of abuse among young

people, who were crushing the tablets and snorting the powder as a new way of getting a stimulant high. Diver- sion of prescription medications used to treat ADHD was beginning to be a concern.

Since then, the problem of stimulant medication abuse, primarily the nonmedical use of Adderall, has become a major issue in terms of its ability to enhance cognitive and academic performance. Approximately 9 percent of students in a New England liberal arts col- lege reported in 2006 taking stimulants for nonmedical purposes, essentially as a cognitive enhancement. In a surprising (and controversial) survey published in 2008 in Nature, one of the world’s leading scientific journals, 20 percent of respondents said that they were using some kind of cognitive-enhancement drug. In about two-thirds of these cases, the drug was Ritalin. Fourteen hundred presumably healthy people in sixty countries participated in the survey.

The report has sparked a number of interesting questions. Would the quality of cognitive performance really be enhanced, or would the poppers of “smart pills” simply be able to stay awake for a longer period of time? Given what we know about stimulants in gen- eral, it is more likely to be the latter rather than the former. Even if such drugs had a positive effect on per- formance by virtue of increasing the quantity (if not the quality) of the user’s output, there would still be important ethical concerns, both inside and outside academia. In neuroscience laboratories around the world, the quest for “smart pills” is well under way.58 The debate over their use, misuse, or abuse will surely intensify in the years ahead (see Point/Counterpoint II on pages 116–117).

Summary

the History of Cocaine ● Cocaine, one of the two major psychoactive stimu-

lants, is derived from coca leaves grown in the moun- tainous regions of South America.

● During the last half of the nineteenth century, several patent medicines and beverages were sold that con- tained cocaine, including the original (pre-1903) for- mulation for Coca-Cola.

● Sigmund Freud was an early enthusiast of cocaine as an important medicinal drug, promoting cocaine as a cure for morphine dependence and depression. Soon afterward, Freud realized the strong dependence that cocaine can bring about.

Acute effects of Cocaine ● Cocaine produces a powerful burst of energy and

sense of well-being. In general, cocaine causes an ele- vation in the sympathetic autonomic nervous system.

Chronic effects of Cocaine ● Long-term cocaine use can produce hallucinations

and deep depression, as well as physical deterioration of the nasal membranes if cocaine is administered intranasally.

Medical uses of Cocaine ● The only accepted medical application for cocaine is

its use as a local anesthetic.

112 ■ Part two Legally restricted Drugs in our Society

How Cocaine Works in the Brain ● Within the CNS, cocaine blocks the reuptake of

receptors sensitive to dopamine and norepinephrine. As a result, the activity level of these two neurotrans- mitters in the brain is enhanced.

Present-Day Cocaine Abuse ● Compared with the permissive attitude toward cocaine

use seen during the 1970s and early 1980s, attitudes toward cocaine use since the second half of the 1980s have changed dramatically.

● The emergence in the mid-1908s of relatively inex- pensive, smokable crack cocaine expanded the cocaine-abuse problem to new segments of the U.S. population and made cocaine abuse one of the major social issues of our time.

treatment Programs for Cocaine Abuse ● Cocaine abusers can receive treatment through inpa-

tient programs, outpatient programs, or a combination of the two. Relapse is a continual concern for recover- ing cocaine abusers.

Amphetamines ● Amphetamines, the second of the two major psy-

choactive stimulants, have their origin in a Chinese medicinal herb, used for thousands of years as a bron- chial dilator; its active ingredient, ephedrine, was iso- lated in 1887.

● The earliest form of amphetamine (brand name: Ben- zedrine) was developed in 1927 as a synthetic form of ephedrine. By the 1930s, various forms of amphet- amines, specifically d-amphetamine and metham- phetamine, became available around the world.

Acute and Chronic effects of Amphetamines ● Amphetamine is effective as a general arousing agent,

as an antidepressant, and as an appetite suppressant,

in addition to its ability to keep people awake for long periods of time.

● The acute effects of amphetamines resemble those of cocaine, but amphetamines (when taken in large doses) have the particular feature of producing symp- toms of paranoia, delusions, hallucinations, and vio- lent behaviors, referred to as amphetamine psychosis. The bizarre behaviors of the “speed freak” illustrate the dangers of chronic amphetamine abuse.

Present-Day Patterns of Methamphetamine Abuse ● With the emphasis on cocaine abuse during the

1980s, amphetamine abuse was less prominent in the public mind. Recently, however, there has been a resurgence of amphetamine-abuse cases involving methamphetamine, particularly in nonurban regions of the United States.

● Treatment for methamphetamine abuse generally follows along the same lines as treatment for cocaine abuse.

Medical and Nonmedical uses for Amphetamines and Similar Stimulant Drugs ● Amphetamine-like stimulant drugs have been devel-

oped for approved medical purposes. ● Methylphenidate (brand name: Ritalin), atomoxetine

(brand name: Strattera), and dextroamphetamine (brand name: Adderall) are three examples of drugs prescribed for children diagnosed with attention- deficit/hyperactivity disorder (ADHD). Recently, there has been growing concern about the nonmedical use of these medications, either for recreational or “cogni- tive enhancement” purposes.

● Other medical applications for amphetamine-like drugs include their use as a treatment for narcolepsy and as a means for the temporary relief of nasal congestion.

Key terms

amphetamine, p. 104 amphetamine psychosis, p. 105 attention-deficit/ hyperactivity

disorder (ADHD), p. 109

cocaine, p. 90 cocaine hydrochloride, p. 97 cocaine psychosis, p. 95 crack cocaine or crack, p. 97

d-amphetamine, p. 103 formication, p. 93 free-base cocaine, p. 97 ice, p. 106

kindling effect, p. 96 methamphetamine, p. 103

Endnotes

1. Rosencan, J. S., and Spitz, H. I. (1987). Cocaine recon- ceptualized: Historical overview. In H. I. Spitz and J. S. Rosencan (Eds.), Cocaine abuse: New directions in treatment and research. New York: Brunner/ Mazel, p. 5.

2. Inglis, B. (1975). The forbidden game: A social history of drugs. New York: Scribner, pp. 49–50. Montoya, I. D., and Chilcoat, H. D. (1996). Epidemiology of coca deriv- atives use in the Andean region: A tale of five countries. Substance Use and Misuse, 31, 1227–1240.

Chapter 4 the Major Stimulants: Cocaine and amphetamines ■ 113

3. Jaffe, J. (1985). Drug addiction and drug abuse. In L. S. Goodman and A. Gilman (Eds.), The pharmacologi- cal basis of therapeutics (7th ed.). New York: Macmillan, p. 552.

4. Nahas, G. G. (1989). Cocaine: The great white plague. Middlebury, VT: Paul S. Eriksson, pp. 154–162.

5. Kusinitz, M. (1988). Drug use around the world. New York: Chelsea House Publishers, pp. 91–95.

6. Karch, S. B. (2009). The pathology of drug abuse (4th ed.). Boca Raton, FL: CRC Press, pp. 9–19. Nuckols, Caldwell C. (1989). Cocaine: From dependency to recovery (2nd ed.). Blue Ridge Summit, PA: Tab Books.

7. Brecher, E. M., and the editors of Consumer Reports (1972). Licit and illicit drugs. Boston: Little, Brown, p. 270. Weiss, R. D., and Mirin, S. M. (1987). Cocaine. Washington, DC: American Psychiatric Press, p. 6.

8. McKim, W. A., and Hancock, S. D. (2013). Drugs and behavior (7th ed.). Boston: Pearson,, p. 230.

9. Erickson, P. G.; Adlaf, E. M.; Murray, G. F.; and Smart, R. G. (1987). The steel drug: Cocaine in perspective. Lexington, MA: D.C. Heath, p. 9.

10. Musto, D. (1973). The American disease: Origins of nar- cotic control. New Haven, CT: Yale University Press.

11. Jones, E. (1953). The life and work of Sigmund Freud, Vol. 1. New York: Basic Books, p. 81. White, W. L. (1998). Slaying the dragon: The history of addiction treat- ment and recovery in America. Bloomington, IL: Chestnut Health Systems, pp. 108–119.

12. Ibid., Jones, p. 84. 13. Brecher, Licit and illicit drugs, pp. 272–280. 14. National Institute on Drug Abuse (2010, March). NIDA

InfoFacts: Cocaine. Bethesda, MD: National Institute on Drug Abuse.

15. Philips, J. L., and Wynne, R. D. (1974). A cocaine bibliography—nonannotated. Rockville, MD: National Institute on Drug Abuse, 1974. Cited in E. L. Abel. (1985). Psychoactive drugs and sex. New York: Plenum Press, p. 100.

16. Schneir A. B. (2008). Medical consequences of the use of cocaine and other stimulants. In J. Brick, (Ed.), Handbook of the medical consequences of alcohol and drug abuse (2nd ed.). New York: Routledge, pp. 344–354. Kaufman, M. J.; Levin, J. M.; Ross, M. H.; Lange, N.; Rose, S. L.; et al. (1998). Cocaine-induced cerebral vasoconstriction detected in humans with magnetic resonance angiography. Journal of the American Medical Association, 279, 376–380.

17. Experiment in Memphis suggests many drive after using drugs (1994, August 28). New York Times, p. 30.

18. Information courtesy of the American Academy of Otolaryngology—Head and Neck Surgery, March 1998.

19. Volkow, N. D.; Wang, G-J; Fowler, J. S.; Logan, J.; Gatley, S. J.; et al. (1997). Decrease in striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature, 386, 830–833. Volkow, N. D., and Ting-Kai, L. (2004). Drug addiction: The neurobiology of behaviour gone awry. Nature Reviews/Neuroscience, 5, 963–970.

20. Robinson, T. E. (1993). Persistent sensitizing effects of drugs on brain dopamine systems and behavior: Implica- tions for addiction and relapse. In S. G. Korenman and J. D. Barchas (Eds.), The biological basis of substance abuse. New York: Oxford University Press, pp. 373–402. Weiss and Mirin, Cocaine, pp. 48–49.

21. Demarest, M. (1981, July 6). Cocaine: Middle class high. Time, pp. 56–63. Quotation on p. 56.

22. Kaplan, H. I.; Freedman, A. M.; and Sadock, B. J. (1980). Comprehensive textbook of psychiatry. Vol. 3. Baltimore, MD: Williams & Wilkins, p. 1621.

23. Flynn, J. C. (1991). Cocaine: An in-depth look at the facts, science, history, and future of the world’s most ad- dictive drug. New York: Birch Lane/Carol Publishing, pp. 38–46.

24. Humphries, D. (1998). Crack mothers at 6: Prime-time news, crack/cocaine, and women. Violence against Women, 4, 45–61. Massing, M. (1998). The fix. New York: Simon and Schuster, p. 41. Singer, L.T.; Minnes, S.; Short, E.; Arendt, R.; Farkas, K.; et al. (2004). Cog- nitive outcomes of preschool children with prenatal cocaine exposure. Journal of the American Medical As- sociation, 291, 2448–2456.

25. Furst, R. T.; Johnson, B. D.; Dunlap, E.; and Curtis, R. (1999). The stigmatized image of the “crack head”: A sociocultural exploration of a barrier to cocaine smok- ing among a cohort of youth in New York City. Deviant Behavior, 20, 153–181.

26. Substance Abuse and Mental Health Services Adminis- tration (2012). Results from the 2011 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Adminis- tration, Table 1.1A.

27. Substance Abuse and Mental Health Services Adminis- tration (2013). Drug Abuse Warning Network: National estimates of drug-related emergency department visits 2004–2011. Rockville, MD: Substance Abuse and Mental Health Services, Excel files.

28. Nuckols, Cocaine, p. 42. 29. Ibid., pp. 71–72. 30. Weiss and Mirin, Cocaine, p. 125. 31. Siegel, S. (1999). Drug anticipation and drug addiction.

The 1998 H. David Archibald Lecture. Addiction, 94, 1113–1124.

32. Friedman, R. A. (2010, August 31). Lasting pleasures, robbed by drug abuse. New York Times, p. D6.

33. Shine, B. (2000, March). Some cocaine abusers fare bet- ter with cognitive-behavioral therapy, others with 12-step programs. NIDA Notes, 15 (1), 9–11.

34. Brodie, J. D.; Case, B. G.; Figuerosa, E.; Dewey, S. L.; Robinson, J. A.; and Laska, E.M. (2009). Randomized, double-blind, placebo-controlled trial of vigabatrin for the treatment of cocaine dependence in Mexican parolees. American Journal of Psychiatry, 166, 1269–1277. Sergo, P. (2008, April/May). New weapons against cocaine addiction. Scientific American Mind, pp. 54–57.

114 ■ Part two Legally restricted Drugs in our Society

35. Barnes, D. M. (1988). Breaking the cycle of addiction. Science, 241, p. 1029. Whitten, L. (2005, August). Cocaine-related environmental cues elicit physiological stress responses. NIDA Notes, 20(1), pp. 1, 6–7.

36. Brecher, Licit and illicit drugs, pp. 282–283. 37. Greaves, G. B. (1980). Psychosocial aspects of amphet-

amine and related substance abuse. In J. Caldwell (Ed.), Amphetamines and related stimulants: Chemical, biologi- cal, clinical, and sociological aspects. Boca Raton, FL: CRC Press, pp. 175–192.

38. Schneir, Handbook , 354-356. Substance Abuse and Mental Health Services Administration (2013). Drug Abuse Warning Network, National estimates of drug- related emergency department visits 2004–2011. Rockville, MD: Substance Abuse and Mental Health Services Administration, Excel files.

39. Goode, E. (2005). Drugs in American society (6th ed.). New York: McGraw-Hill College, p. 276.

40. Bai, M. (1997, March 31). White storm warning: In Fargo and the prairie states, speed kills. Newsweek, pp. 66–67. Quotation by M. A. R. Kleiman, p. 67.

41. Goode, Drugs in American society, p. 276. Sheff, D. (2008). Beautiful boy: A father’s journey through his son’s addiction. New York: Houghton Mifflin. Sheff, N. (2008). Tweak: Growing up with methamphetamine. New York: Ginee See Books/Atheneum Books for Young Readers, pp. 113–115.

42. Ernst, T. Chang, L.; Leonido-Yee, M.; and Speck, O. (2000). Evidence for long-term neurotoxicity associ- ated with methamphetamine abuse: A 1H MRS study. Neurology, 54, 1344–1349. London, E. D.; Simon, S. L.; Berman, S. M.; Mandelhern, M. A.; et al. (2004). Mood disturbances and regional cerebral metabolic abnormali- ties in recently abstinent methamphetamine abusers. Archives of General Psychiatry, 61, 73–84.

43. Young, S. (1989, July). Zing! Speed: The choice of a new generation. Spin magazine, pp. 83, 124–125. Reprinted in E. Goode (Ed.) (1992). Drugs, society, and behavior 92/93. Guilford, CT: Dushkin Publishing, p. 116.

44. Substance Abuse and Mental Health Services Adminis- tration, Results from the 2011 National Survey on Drug Use and Health: Detailed tables, Table 1.1A.

45. Butterfield, F. (2004, January 4). Across rural America, drug casts a grim shadow. New York Times, p. 10. Car- nevale Associates (2011, March) . Policy Brief: Update: The changing landscape of the methamphetamine epidemic. Gathersburg, MD: Carnevale Associates. Harris, G. (2005, December 15). Fighting methamphetamine, lawmakers reach accord to curb sales of cold medicines. New York Times, p. A33. Johnson, D. (2004, March 8). Policing a rural plague: Meth is ravaging the Midwest. Newsweek, p. 41. National Association of Counties (2006, January). The meth epidemic in America. Washington, DC: National Association of Counties. National Drug Intelligence Center (2011, August). Drug Enforcement Administra- tion (2013). Methamphetamine lab incidents. Drug

Enforcement Administration, U.S. Department of Justice, Washington, DC.

46. Jacobs, A. J. (2004, January 12). The beast in the bath- house: Crystal meth use by gay men threatens to reignite an epidemic. New York Times, pp. B1, B5. Shernoff, M. (2005, July–August). Crystal’s sexual persuasion. The Gay & Lesbian Review, pp. 24–26.

47. Zickler, P. (2001). Methamphetamine, cocaine abusers have different patterns of drug use, suffer different cogni- tive impairments. NIDA Notes, 16 (5), 11–12.

48. Gawin, F. H., and Ellinwood, E. H. (1988). Cocaine and other stimulants: Action, abuse, and treatment. New England Journal of Medicine, 318, 1173–1182. National Institute of Justice (1999, May). Meth matters: Report on methamphetamine users in five western cities. Washing- ton, DC: National Institute of Justice, U.S. Department of Justice. Quotation on p. xii.

49. Julien, R. M. (2005). A primer of drug action (10th ed.). New York: Worth, pp. 390–405.

50. Findling, R. L. (2008). Evolution of the treatment of at- tention-deficit/hyperactivity disorder in children. Clinical Therapeutics, 30, 942–957. Julien, A primer of drug ac- tion, pp. 390–391. Wilens, T. E. (2003). Drug therapy for adults with attention-deficit hyperactivity disorder. Drugs, 63, 2385–2411. Wilens, T. E., and Fusillo, S. (2007). When ADHD and substance use disorders intersect: Re- lationship and treatment implications. Current Psychiatry Reports, 9, 408–414.

51. Julien, A primer of drug action, pp. 395–396. 52. The MTA Cooperative Group (1999). A 14-month random-

ized clinical trial of treatment strategies for attention-deficit/ hyperactivity disorder. Archives of General Psychiatry, 56, 1073–1086.

53. Nissen, S. E. (2006, April 6). ADHD drugs and cardio- vascular risks. New England Journal of Medicine, pp. 1445–1448.

54. Wilens, T. E.; Faraone, S. V.; Biederman, J.; and Gu- nawardene, S. (2003). Does stimulant therapy of attention deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics, 111, 179–185.

55. Julien, A primer of drug action, p. 395. Volkow, N. D.; Wang, G-J; Kollins, S. H.; Wigal, T. L.; Newcorn, J. H.; et al. (2009). Evaluating dopamine reward pathway in ADHD: Clinical implications. Journal of the American Medical Association, 302, 1084–1091.

56. Green, P. M., and Stillman, M. J. (1998). Narcolepsy: Signs, symptoms, differential diagnosis, and manage- ment. Archives of Family Medicine, 7, 472–478. Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulen- berg, J. E. (2012a). Monitoring the Future: National survey results on drug use, 1975–2011. Vol. I: Secondary school students 2011. Ann Arbor, MI: Institute for Social Research, The University of Michigan, Table 2-1.Tuller, D. (2002, January 8). A quiet revolution for those prone to nodding off. New York Times, p. F7.

Chapter 4 The Major Stimulants: Cocaine and Amphetamines ■ 115

57. Julien, R. M. (1998). A primer of drug action (8th ed.). New York: Freeman, pp. 141–143.

58. Arria, A. M.; Caldeira, K. M.; O’Grady, K. E.; Vincent, K. B.; et al. (2008). Nonmedical use of prescription stimulants among college students: Associations with attention-deficit-hyperactivity disorder and polydrug use. Pharmacotherapy, 28, 156–169. Carroll, B.C.; McLaughlin, T. J.; and Blake, D. R. (2006). Patterns and knowledge of nonmedical use of stimulants among college students. Archives of Pediatric and Adolescent Medicine, 160, 481–485. Greely, H.; Sahakian, B.; Harris, J. Kessler, R. C.; Gazzaniga, M.; et al. (2008). Toward responsible use of cognitive-enhancing drugs by the healthy. Nature, 456, 702–705. Harris, J., and Quigley, M. (2008). Commentary on “Professor’s little helper”: Humans

have always tried to improve their condition. Nature, 451, 521 Schermer, M. (2008). On the argument that enhancement is “cheating.” Journal of Medical Ethics, 34, 85-88. Stix, G. (2009, October). Turbocharging the brain. Scientific American, 46–55 Substance Abuse and Mental Health Services Administration (2009, April 7). Nonmedical use of Adderall among full-time college students. The NSDUH Report, pp.1–4. Talbot, M.. (2009, April 27). Brain gain: The underground world of “neuroenhancing” drugs. New Yorker, pp. 32–43. Wilens, T. E.; Adler, L. A.; Adams, J.; Sgambati, S. E; Rotrosen, J.; et al. (2008). Misuse and diversion of stimulants prescribed for ADHD: A systematic review of the literature. Journal of the American Academy of Child and Adolescent Psychiatry, 47, 21–31.

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The following discussion of view- points presents the opinions of people on both sides of the contro- versial issue of whether cognitive performance-enhancing drugs, origi- nally intended for the treatment of ADHD and other behavioral disor- ders, should be used by healthy peo- ple to enhance their behavior on the job or in an academic or research environment. Read them with an open mind. You don’t have to come up with the final answer, nor should you necessarily agree with the argu- ment presented last. Many of the ideas in this feature come from the sources listed.

POiNT In a surprising survey report pub- lished in 2008 in Nature, one of the world’s leading scientific jour- nals, 20 percent of respondents said that they took some kind of cognitive-enhancement drug; about two-thirds of these cases in- volved Ritalin, an FDA-approved medication for the treatment of attention-deficit/hyperactivity dis- order (ADHD), simply to enhance their mental performance. Four- teen hundred presumably healthy people in sixty different countries participated in the survey. This is a ghastly example of scientists and scholars engaging in uncontrolled pharmacological experiment a- tion. Here was evidence of psy- chostimulant drugs, intended for therapeutic use for a specific disor- der, being used by healthy adults

to improve their productivity. Isn’t anything sacred anymore?

COUNTERPOiNT How is this different from dos- ing yourself with caffeine with a couple of strong cups of coffee to get through that boring afternoon meeting or that all-nighter to fin- ish a term paper? You are taking a psychoactive drug (caffeine) to enhance your cognitive perfor- mance, just as others have been doing for centuries. How is it dif- ferent from t aking a prescribed beta-blocker medication to help reduce situational anxiety?

POiNT Granted that we already engage in a form of cognitive performance enhancement with the consump- tion of caffeine. But let’s t alk about a level playing field. Caf- feine can be obtained anywhere; it’s ubiquitous. In contrast, Ritalin is a prescription drug. Were the pills obtained through prescrip- tions written for them, and if so, were the prescriptions obtained under false pretenses? This is dishonest at best, illegal at worst. The Nature survey reported that a third of the respondents had obtained their drugs through the Internet, where the industry is largely unregulated. They ran the risk of great harm to themselves. They may have ingested all sorts of contaminants. They may have risked dying.

COUNTERPOiNT Health risks from contaminated drugs ordered through the Internet don’t seem to be higher in these cases than health risks among peo- ple who are ordering their prescrip- tions online to save money. I don’t buy the argument that obtaining cognitive performance-enhancing drugs through the Internet suddenly plunges you into the dark world of illicit drug abuse. Besides, the side effects of Ritalin are relatively mild—moderate increases in heart rate and blood pressure. When these drugs went through the FDA approval process, clinical trials (see Chapter 14) revealed no serious cardiac problems in healthy adults. There was a problem in older adults and in those with preexisting car- diovascular problems, but generally these drugs were deemed safe and effective if you’re healthy.

POiNT You’re missing a bigger point here. Where is your basic sense of fair play? Not everyone has equivalent access. It’s morally wrong to put one person at an advantage over other people who might be with- out access to these enhancements.

COUNTERPOiNT There isn’t equivalent access to SAT-preparation courses either. Yet people don’t discount a high SAT score just because someone else couldn’t afford the expense of such preparation.

P A r t t w o

Legally restricted Drugs in our Society

Point/Counterpoint II

Should Cognitive Performance-Enhancing Drugs Be Used by Healthy People?

Chapter 4 The Major Stimulants: Cocaine and Amphetamines ■ 117

Point That may be true, but there is an effort to provide SAT preparation courses and instruction to as wide a population as possible, through a number of community programs. To make the same argument here, you would have to ensure that as many people as possible have ac- cess to Ritalin. Isn’t this getting absurd?

Until that day comes (and let us hope it will not), how do we make an ultimate judgment about a person’s achievements in life? Do we need an asterisk next to someone’s Nobel or Pulitzer Prize if it was determined that cognitive performance-enhancing drugs were used? Such a move is being considered for sports re- cords achieved by athletes who were taking anabolic steroids and other performance-enhancing drugs when they set these records. Why not in the case of cognitive performance-enhancing drugs? Conversely, would a disclaimer (perhaps a negative urinalysis) be required on a professor’s tenure candidacy file to indicate that her or his productivity was achieved

without the aid of cognitive perfor- mance-enhancing drugs?

CounterPoint The current phenomenon of cog- nitive performance-enhancing drugs such as Ritalin is only the most recent inst ance in a long history of human enhancement. People have always taken steps to improve the human condition or the circumstances under which they work and serve society. Isn’t it an obligation to use one’s full potential and resources to the greatest benefit of humanity? If cognitive performance-enhancing drugs advance that process, the drugs are serving humankind.

Consider it a ment al form o f c o s m e t i c s u r g e r y. B e s i d e s , it hasn’t been scientifically de- termined that cognitive perfor- mance-enhancing drugs actually make you smarter. Probably, at most, they allow you to stay alert l o n g e r t h a n y o u w o u l d h a v e under ordinary circumst ances. But if their effects turn out to be more profound than that, we need to consider carefully the is- sues of responsible use.

Critical Thinking Questions for Further Debate 1 Suppose you are a new employee

in a high-pressure corporation where your co-workers are in- gesting a cognitive performance- enhancing drug such as Ritalin to increase their work productivity, but you have a preexisting car- diovascular disorder that would make taking this drug unwise. There is no overt coercion to join in with your co-workers, but you know that you will be at a disad- vantage in terms of promotion and salary incentives if you don’t. Is this a form of discrimination in the workplace?

2 S u p p o s e y o u a r e t a k i n g a chemistry exam, and you know that a person next to you took Ritalin in order to study 50 per- cent longer than you were able to without taking a cognitive performance-enhancing drug. That other person outscores you by a full letter grade. Do you have any recourse in ap- pealing your grade?

Point/Counterpoint iii can be found on pages 246–247.

Sources: Carey, B. (2008, March 9). Brain enhancement is wrong, right? New York Times, Week in Review, pp. 1–2. Greely, H.; Sahakian, B.; Harris, J.; Kessler, R. C.; Gazzaniga, M.; et al. (2008). Toward responsible use of cognitive-enhancing drugs by the healthy. Nature, 456, 702–705. Harris, J., and Quigley, M. (2008). Commentary on “Professor’s little helper”: Humans have always tried to improve their condition. Nature, 451, 521. Monatersky, R.D. (2008, April 25). Some profes- sors pop pills for an intellectual edge. The Chronicle of Higher Education, pp. A1, A10. Sahakian, B., and Morein-Zamir, S. (2007). Professor’s little helper. Nature, 450, 1157–1159. Schermer, M. (2008). On the argument that enhancement is cheating. Journal of Medical Ethics, 34, 85–88.

118

After you have completed this chapter, you should have an understanding of

▶ The history of opium and opioid drugs

▶ The effects of opioid drugs on the mind and body

▶ The neurochemical basis for opioid drug effects

▶ Patterns of heroin abuse

▶ The potential lethality of heroin abuse

▶ The issue of controlled heroin intake

▶ Treatment strategies for heroin dependence

▶ Uses of opioid pain medications

▶ Current use and abuse of Oxycodone, OxyContin, Vicodin, and other opioid pain medications

Opioids: Opium, Heroin, and Opioid Pain Medications

C h a p t e r

5

I’m 72 years old, a grandmother of five and a great-

grandmother too, living alone since my husband passed

away five years ago. Since my spinal stenosis surgery a

year and a half ago, life is a nightmare. I have to say that

OxyContin saved my life, even though I call it a “fake”

life. I can do the little things sure, like doing the dishes,

straightening up the house for a while, without letting

people know that I’m crying inside. But the fact is that I’m

90 percent disabled and miserable all the time. I know it

could be worse; if it was, I think I would end it all tomorrow.

So please don’t take away my medicine. It’s keeping

me around. Maybe I’m addicted, I don’t know. Maybe if

the doctor took away my OxyContin, I would try to get it

any way I could. I’d probably be out there with those peo-

ple who hold up those drugstores.1

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 119

There is no escaping the love–hate relationship we have with opium and a category of similarly acting drugs that are collectively known as opioids. Here is a group of psychoactive drugs with the astonishing ability to banish pain from our lives and, at the same time, the potential for enslaving our minds. This chapter will concern itself with the medical uses and recreational abuses of opioids.

Historically, opioid drugs have been referred to as narcotics (from the Greek word for “stupor”), in that they produce a dream-like effect on the user and at higher doses induce a state of sleep. As noted in Chapter 2, the term “narcotic” was used at one time inappropriately to mean any illicit psychoactive drug or at least any drug that caused some degree of depen- dence, including such unlikely examples as cocaine and amphetamine, which are anything but sleep-inducing. Ironically, specific drugs are currently available that have no relationship to opium or opioids but are far more effective in inducing sleep (see Chapter 13).

Opioids can be divided into four broad categories of drugs.

■ The first category comprises three natural compounds that are directly extracted from opium itself: mor- phine, codeine, and thebaine. All opioid derivatives have their origin in these compounds.

■ The second category comprises derivative com- pounds that are created by making specific changes in the chemical composition of morphine. Examples are heroin, hydromorphone (brand name: Dilaudid), oxymorphone (brand names: Numorphan, Opana), and the extended-release form of oxymorphone (brand name: Opana ER).

■ The third category comprises derivative compounds that are created by making specific changes in the chemical composition of codeine or thebaine. Examples are oxycodone (brand names: Percodan,

Percocet), the controlled-release form of oxycodone (brand name: OxyContin), and hydrocodone (brand names: Hycodan, Vicodin).

■ The fourth category comprises drugs that are not chemically related to any of the natural extracts of opium but rather are synthesized entirely in the labo- ratory.  As a result, they are often referred to as synthetic opioids.  Examples include methadone, meperidine (brand name: Demerol), propoxyphene (brand names: Darvon, Darvocet), LAAM (brand name: Orlaam), tramadol (brand names: Ultram, Ultracet), and buprenorphine (brand names: Subutex, Suboxone).

Figure 5.1 shows some of the major opioid drugs that are currently available for medical and nonmedical uses.

Opium in History

Like cocaine, the history of heroin and the other opioid drugs can be traced back to faraway times and places. This particular story begins with a method of harvest- ing of raw opium that has not changed much in more than three thousand years. It takes place today in remote villages of Myanmar (formerly Burma), Laos, Thailand, Afghanistan, Kazakhstan, Mexico, Colombia, Peru, and other countries where the weather is hot and labor is cheap. The source is the opium poppy, known by its botanical name as Papaver somniferum (literally “the poppy that brings sleep”), an annual plant growing three to four feet high. Its large flowers are typically about four or five inches in diameter and can be white, pink, red, or purple. This variety is the only type of poppy that pro- duces opium; common garden plants such as the red Oriental poppy and the yellow California poppy look similar but do not produce psychoactive effects.

The process is simple. When the petals of the opium poppy have fallen but the seed capsule of the plant underneath the petals is not yet completely ripe, laborers make small, shallow incisions in the capsules, allowing a milky white juice to ooze out during the night. The next day, this substance will have oxidized and hardened by contact with the air. Now they go from plant to plant, collecting the juice onto large poppy

by the numbers . . .

281,000 Number of persons in the United States over 12 years who reported in 2011 having used heroin in the past month

434,000 Number of persons in the United States over 12 years who reported in 2011 having used OxyContin for nonmedical purposes in the past month

Source: Substance Abuse and Mental Health Services Administration (2012). Results from the 2011 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Administration, Table 1.1A.

opioids (OH-pee-oids): Drugs with analgesic (pain reducing) properties that act in the brain like opium.

narcotics: A general term technically referring to opiate- related or opiate-derived drugs. It is often mistakenly used to include several other illicit drug categories as well.

opium: An analgesic and euphoriant drug acquired from the dried juice of the opium poppy.

120 ■ Part Two Legally Restricted Drugs in Our Society

leaves. At this point, opium is reddish brown in color and has the consistency of heavy syrup. Later it will darken further and form small gum-like balls.2

The first written references to opium date back to the early third century b.c., but we can be fairly sure that it was used for at least a thousand years before that. A ceramic opium pipe has been excavated in Cyprus,

dating from the Late Bronze Age, about 1200 b.c. Cypriot vases from that era depict incised poppy cap- sules. Evidence contained in the Ebers Papyrus writings (see Chapter 1) shows that Egyptians were knowledge- able about the medicinal value of opium.3

In the second century A.D., Claudius Galen, a famous Greek physician and surgeon to Roman gladi- ators, recommended opium for practically everything. He wrote that it

. . . resists poison and venomous bites, cures chronic headache, vertigo, deafness, apoplexy, dimness of sight, loss of voice, asthma, coughs of all kinds, spit- ting of blood, tightness of breath, colic, . . . jaun- dice, hardness of the spleen, . . . urinary complaints, fever, . . . leprosies, the troubles to which women are subject, melancholy, and all pestilences.4

Galen’s enthusiasm for the instrumental use of opium is an early example of “over-prescribing.” Interestingly, however, there are no records in ancient times that refer to the recreational use of opium or to any problems of opium dependence.5

Western Europe was introduced to opium in the eleventh and twelfth centuries by returning crusaders

oxycodone (Percodan, Percocet)

controlled-release oxycodone (OxyContin)

Opium Extracts

morphine

heroin

methadone meperidine (Demerol)

LAAM (Urlaam)

propoxyphene (Darvon, Darvocet)

tramadol (Ultram, Ultracet)

buprenorphine (Subutex, Suboxone)

hydromorphone (Dilaudid)

oxymorphone (Numorphan, Opana IR)

extended-release oxymorphone (Opana ER)

codeine

hydrocodone (Hycodan, Vicodin)

Opioid Derivatives

Synthetic Opioids

opium

thebaine

F i g u r e 5 . 1

Classifying major opioid drugs: Opium extracts, opioid derivatives, and synthetic opioids (Brand names are shown in parentheses.)

Note: Hydrocodone can also be derived from thebaine. A more complete listing of opioid pain medications appears in Table 5.2 on page 136.

Sources: Physicians’ desk reference (67th ed.) (2013). Montvale, NJ: PDR Network. Raj, P. Prithvi (1996). Pain medicine: A comprehensive review. St. Louis: Mosby, pp. 126–153.

Local villagers harvest opium in a poppy field in the Golestan district of Farah province in Afghanistan.

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 121

who had learned of it from the Arabs. During the first stir- rings of modern medicine in Europe, opium began to be regarded as a therapeutic drug. In 1520, a physician named Paracelsus, promoting himself as the foremost medical authority of his day, introduced a medicinal drink combin- ing opium, wine, and an assortment of spices. He called the mixture laudanum (derived from the Latin phrase meaning “something to be praised”), and before long the formula of Paracelsus was being called the “stone of immortality.” Even though Paracelsus himself denounced many of the doctrines of Galen and earlier physicians in history, he continued the time-honored tradition of recom- mending opium for practically every known disease.

In 1680, the English physician Thomas Sydenham, considered the father of clinical medicine, introduced a highly popular version of opium drink similar to that of Paracelsus, called Sydenham’s Laudanum. For the next two hundred years or so, the acceptable means of taking opium among Europeans and then Americans would be in the form of a drink, either Sydenham’s recipe or a host of variations. Sydenham’s enthusiasm for the drug was no less than that of his predecessors. “Among the remedies,” he wrote, “which it has pleased Almighty God to give man to relieve his sufferings, none is so universal and so efficacious as opium.”6 The popularity of opium drink- ing eventually led to the emergence of opium as a major recreational drug in Europe and the United States.

The Opium War

Sometime in the eighteenth century, China invented a novel form of opium use, opium smoking, which eventually became synonymous in the Western mind with China itself. However, for at least eight hundred years before that, the Chinese had used opium only in a very limited way. They took it almost exclusively on a medicinal basis, consuming it orally in its raw state as a highly effective painkiller and treatment for diarrhea (see Table 5.1).

The picture changed dramatically in the eigh- teenth century, strangely enough, when the British people discovered and fell in love with Chinese tea. Sensing a business opportunity, British merchants in China sought a way to buy Chinese tea and transport it home for a handsome profit. But what could they sell to the Chinese in exchange? The problem was that there were few, if any, commodities that China really wanted from the outside. In their eyes, the rest of the world was populated by “barbarians” with an inferior culture, offering little or nothing the Chinese people needed.

This late-nineteenth-century illustration of young working girls in a New York City opium den was part of a widespread media campaign at the time to outlaw the smoking of opium.

TAble 5.1

Symptoms of administering heroin and of withdrawing heroin

AdminisTering WiTHdrAWing

Lowered body temperature Elevated body temperature

Decreased blood pressure Increased blood pressure

Skin flushed and warm Piloerection (gooseflesh)

Pupil constriction Pupil dilation

Constipation Diarrhea

Respiratory depression Yawning, panting, sneezing

Drying of secretions

Decreased sex drive

Tearing, runny nose

Spontaneous ejaculations and orgasms

Muscular relaxation Restlessness, involuntary twitching and kicking movements*

Nodding, stupor Insomnia

Analgesia Pain and irritability

Euphoria and calm Depression and anxiety

*The source of the expression “kicking the habit.”

Source: Adapted from Grilly, D. M., and Salamone, J. D. (2012). Drugs, brain, and behavior (6th ed.). Boston: Pearson Education, p. 298.

122 ■ Part Two Legally Restricted Drugs in Our Society

The answer turned out to be opium. In 1773, British forces had conquered Bengal Province in India and suddenly had a monopoly on raw opium. Here was an opportunity to introduce Indian-grown opium to China as a major item of trade. Despite the under- standable opposition by the Chinese government, opium soon flooded into the country, smuggled in by local British and Portuguese merchants, which enabled the British government and its official trade represen- tative, the East India Company, to maintain a pub- lic image of not being directly involved in the opium trade. Huge quantities of opium found a ready market in southern port cities such as Canton. Not surprisingly, opium smoking and opium dependence soon became a major social problem. Repeated edicts by the Chinese emperor to reduce the use of opium within China or cut the supply line from India failed. The situation was out of control.7

In 1839, tensions had reached a peak. In a historic act of defiance against the European powers, includ- ing Britain, an imperial commissioner appointed by the Chinese emperor to deal with the opium problem once and for all, confiscated a shipment of opium and burned it publicly in Canton. His courageous act, how- ever, was not appreciated by the British. Events esca- lated shortly thereafter, until open fighting broke out between Chinese and British soldiers. The Opium War had begun.

By 1842, British artillery and warships had over- whelmed a nation unprepared to deal with European firepower. In a humiliating treaty, China was forced to sign over to Britain the island of Hong Kong and its harbor (until the distant year of 1997), grant to British merchants exclusive trading rights in major Chinese ports, and pay a large amount of money to reimburse Britain for losses during the war. Despite these agree- ments, fighting broke out again between 1858 and 1860; with French and American forces joining the British. In a treaty signed in 1860, China was required to legalize opium within its borders. The Opium War succeeded in opening up the gates of China, much against its will, to the rest of the world.8

Opium in Britain and the United States

To the average British citizen in the mid-1800s, the Opium War in China was purely a trade issue, a faraway conflict with little or no direct impact on one’s daily life. Nonetheless, opium itself was everywhere. The

important difference between China and Britain with respect to opium was not in the extent of its consump- tion but in the way it was consumed. The acceptable form of opium use in Victorian England was opium drinking in the form of laudanum, whereas the Asian practice of opium smoking was linked to a perceived lifestyle of vice and degradation and associated with the very lowest fringes of society. The contrast was strik- ingly ironic. Opium dens, with all the evil connotations that the phrase has carried into modern times, were the places where opium was smoked; the respectable parlors of middle-class British families were the places where opium was drunk.

Supplies of British opium were unlimited, cheaper than gin or beer. Medical opinion was at most divided on the question of any potential harm; there was no neg- ative public opinion and seldom any trouble with the police. As long as there were no signs of opium smoking, a chronic opium abuser was considered no worse than a drunkard. Nearly all infants and young children in Britain during this period were given opium, often from the day they were born. Dozens of laudanum-based pat- ent medicines (with appealing names such as Godfrey’s Cordial, A Pennysworth of Peace, and Mrs. Winslow’s Soothing Syrup) were used to dull teething pain or colic, or merely to keep the children quiet. The admin- istration of opium to babies was particularly attractive in the new, industrial-age lifestyle of female workers, who had to leave their infants in the care of elderly women or young children when they went off to work in the factories.9

Out of this climate of acceptance sprang a new cultural phenomenon: the opium-addict writer. Just as LSD and other hallucinogens were to be promoted in the 1960s as an avenue toward a greatly expanded level of creativity and imagination (see Chapter 6), a simi- lar belief was spreading among intellectuals during this period with respect to opium. The leader of the move- ment was Thomas DeQuincey, and his book Confessions of an English Opium Eater, published in 1821, became the movement’s bible. It is impossible to say how many people started to use opium recreationally as a direct result of reading DeQuincey’s ecstatic revelations about “opium eating” (by which he meant opium drinking in the form of laudanum), but there is no doubt that the book made the practice fashionable. English authors enamored with lau- danum included Elizabeth Barrett Browning and Samuel Taylor Coleridge (whose exotic poem Kubla Khan was undoubtedly inspired by an “opium high”).

In many ways, opium consumption in the United States paralleled its widespread use in Britain. In one sur- vey of thirty-five Boston drugstores in 1888, 78 percent

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 123

of the prescriptions that had been refilled three or more times contained opium. Until 1942, opium pop- pies were cultivated in Vermont and New Hampshire, in Florida and Louisiana, and later in California and Arizona. Women outnumbered men in opium use dur- ing the nineteenth century by as much as 3 to 1. As one historian has succinctly put it, “husbands drank alcohol in the saloon; wives took opium at home.”10

Throughout the 1800s, opium coexisted alongside alcohol, nicotine (in tobacco products), and cocaine as the dominant recreational drugs of the day. As late as 1897, the Sears, Roebuck mail-order catalog was adver- tising laudanum for sale for about six cents an ounce. In a clever marketing move directed to alcoholic men, Sears’s “White Star Secret Liquor Cure” was advertised as designed to be added to the gentleman’s after-din- ner coffee so that he would be less inclined to join his friends at the local saloon. In effect, he would probably fall asleep at the table, since the “cure” was opium. If customers became dependent on opium, perhaps as a result of taking the “liquor cure,” then fortunately they could order “A Cure for the Opium Habit,” promoted on another page of the same catalog. If you guessed that the ingredients in this one included a heavy dose of alcohol, you would be right.11 Opium dependence was frequently replaced by cocaine abuse (see Chapter 4), and vice versa.

Given the openness of opium drinking in the nine- teenth-century United States, we can only surmise that the fanatical reaction against the practice of opium smok- ing was based on anti-Chinese prejudice. It is clear that intense hostility existed toward the thousands of Chinese men and boys brought to the West in the 1850s and 1860s to build the railroads. Since most of the Chinese workers were recruited from the Canton area, where

opium trafficking was particularly intense, the practice of opium smoking was well known to them, and it served as a safety valve for an obviously oppressed society of men. In 1875, San Francisco outlawed opium smoking for fear, to quote a newspaper of the time, that “many women and young girls, as well as young men of respect- able family, were being induced to visit the dens, where they were ruined morally and otherwise.”12 No mention was ever made of any moral ruin resulting from drinking opium at home.

A federal law forbidding opium smoking soon fol- lowed, whereas the regulation of opium use by any other means failed to receive legislative attention at that time. By the beginning of the twentieth century, how- ever, the desire for social control of opium dens became overshadowed by the emergence of opium-derived drugs that presented a substantially greater threat to soci- ety than smoked opium.13

Morphine and the Advent of Heroin

In 1803, a German drug clerk named Friedrich Wilhelm Adam Sertürner first isolated a yellowish- white substance in raw opium that turned out to be its primary active ingredient. He called it morphine, in honor of Morpheus, the Greek god of dreams. For the first time, more than three-fourths of the total weight of opium (containing inactive resins, oils, and sugars) could be separated out and discarded. Morphine repre- sented roughly 10 percent of the total weight of opium, but it was found to be roughly ten times stronger than raw opium. All the twenty-five or so opiate products that were eventually isolated from opium were found to be weaker than morphine and formed a far smaller proportion of opium. Besides morphine, other major opiate products were codeine (0.5 percent of raw opium) and thebaine (0.2 percent of raw opium), both of which were found to have a considerably weaker opiate effect.

With the invention of the hypodermic syringe in 1856, morphine could now be injected into the blood- stream rather than administered orally, thus bypassing the gastrointestinal tract and speeding the delivery of effects

morphine: The major active ingredient in opium.

codeine (COH-deen): One of the three active ingredients in opium, used primarily to treat coughing.

thebaine (THee-bayn): One of three active ingredients in opium.

A nineteenth-century advertising card for Mrs. Winslow’s Soothing Syrup, a popular opium remedy, was directed toward young mothers and their children.

124 ■ Part Two Legally Restricted Drugs in Our Society

(see Chapter 3). The new potential of morphine injection coincided with the traumas of the Civil War in the United States (1861–1865) and later of the Franco-Prussian War in Europe (1870–1871). It is not surprising that large numbers of soldiers became dependent on opiates and maintained the condition in the years that followed. After the Civil War, opiate dependence in general was so wide- spread among Union and Confederate veterans that the condition was often called the “soldier’s disease.”14

Against the backdrop of increasing worry about opiate dependence, a new painkilling morphine derivative called heroin was introduced into the market in 1898 by the Bayer Company in Germany, the same company that had been highly successful in developing acetylsalicylic acid as an analgesic drug and marketing it as “Bayer’s Aspirin” (see Chapter 14). About three times stronger than morphine, and strangely enough believed initially to be free of mor- phine’s dependence-producing properties, heroin (from the German heroisch, meaning “powerful”) was hailed as an entirely safe cough suppressant (preferable to codeine) and as a medication to relieve the chest discomfort asso- ciated with pneumonia and tuberculosis. In retrospect, it is incredible that from 1895 to 1905, no fewer than forty medical studies concerning injections of heroin failed to recognize its potential for dependence! The abuse poten- tial of heroin, which we now know exceeds that of mor- phine, was not fully recognized until as late as 1910.15

Why is heroin more potent than morphine? The answer lies in its chemical composition. Heroin consists of two acetyl groups joined to a basic morphine mole- cule. These attachments make heroin more fat-soluble and hence more rapidly absorbed into the brain. Once inside the brain, the two acetyl groups break off, mak- ing the effects of heroin chemically identical to that of morphine. One way of understanding the relation- ship between the two drugs is to imagine morphine as the contents inside a plain cardboard box and the heroin as the box covered with gift wrapping. The con- tents remain the same, but the wrapping increases the chances that the box will be opened.

Opioids in American Society

The end of the nineteenth century marked a turn- ing point in the history of opium and its derivatives. Opioid dependence would never again be treated

casually. By 1900, there were, by one conservative esti- mate, 250,000 opioid-dependent people in the United States, and the actual number could have been closer to 750,000 or more. If we rely on the upper estimate, then we are speaking of roughly one out of every hun- dred Americans, young or old, living at that time. Compare this figure with the 2011 estimate of 281,000 Americans (aged twelve or older) who have used heroin alone within the past month out of a current population that is roughly four times the population in 1900, and you can appreciate the impact that opioid abuse had on American society in the early twentieth century.16

The size of the opioid-abusing population alone at that time probably would have been sufficient grounds for social reformers to seek some way of controlling these drugs, but there was also the growing fear that the problems of opioid abuse were becoming closely associated with criminal elements. There was a gnaw- ing anxiety that opioid drugs were creating a significant disruption in American society. A movement began to build toward instituting some system of governmental regulation.

Opioid Use and Heroin Abuse after 1914

The Harrison Act of 1914 (see Chapter 2) radically changed the face of opioid use and abuse in the United States. It ushered in an era in which the abuser was no longer a victim of drugs worthy of society’s sympathy. Instead, he was now viewed as weak, degenerate, and self-indulgent, a “contaminant” infecting his communi- ty’s social order and, as a result, deserving society’s moral outrage and whatever legal sanction it could devise.17

The situation, however, did not change overnight. Most important, the 1914 legislation did not actually ban opioids. It simply required that doctors register with the Internal Revenue Service the opioid drugs (as well as cocaine and other coca products) that they were prescribing to their patients and pay a small fee for the right to prescribe such drugs. The real impact of the new law came later, in the early 1920s, as a result of several landmark decisions sent down from the U.S. Supreme Court. In effect, the decisions interpreted the Harrison Act more broadly. Under the Court’s inter- pretation of the Harrison Act, no physician was permit- ted to prescribe opioids for “nonmedical” use. In other words, it was now illegal for addicted individuals to obtain drugs merely to maintain their habit, even from a physician. Without a legal source for their drugs, opioid abusers were forced to abandon them altogether or turn

heroin: A chemical derivative of morphine. It is approximately three times as potent as morphine and a major drug of abuse.

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 125

to illegal means, and the drug dealer suddenly provided the only place where opioids, particularly heroin, could be obtained.

Heroin became the perfect black market drug. It was easier and more profitable to refine it from raw opium overseas and ship it into the country in small bags of odorless heroin powder than it was to transport raw opium with its characteristic odor. In addition, because it had to be obtained illegally, heroin’s price tag skyrocketed to thirty to fifty times what it had cost when it was available from legitimate sources.18

With the emergence of restrictive legislation, the demographic picture changed dramatically. No longer were the typical consumers of opioid drugs character- ized as female, predominantly white, middle-aged, and middle-class, as likely to be living on a Nebraskan farm as in a Chicago townhouse. In their place were young, predominantly white, urban adult males, whose opi- oid drug of choice was intravenous heroin and whose drug supply was controlled by increasingly sophisticated crime organizations. In the minds of most Americans, heroin and heroin abusers could be comfortably rel- egated to the social and moral fringes of America.19

Heroin Abuse in the 1960s and 1970s

Three major social developments in the 1960s brought the heroin story back into the mainstream of the United States. The first began in late 1961, when a crackdown on heroin smuggling resulted in a significant shortage of heroin on the street. The price of heroin suddenly increased, and heroin dosages became more adulterated than ever before. Predictably, the high costs of main- taining heroin dependence encouraged new levels of criminal behavior, particularly in urban ghettos. Heroin abuse soon imposed a cultural stranglehold on many African American and Latino communities in major U.S. cities.

A second development, beginning in the 1960s, affected the white majority more directly. Fanned by extensive media attention, a youthful counterculture of hippies, flower children, and the sexually liberated swept the country.

It was a time of unconventional fashions and anti- establishment attitudes. In unprecedented numbers, middle- and upper-class people experimented with illegal drugs to get high. They smoked marijuana; tried the new synthetic properties of amphetamines and barbiturates; rediscovered the almost forgotten

product of the coca plant, cocaine; and, for the first time, people from the mainstream of American life began to experiment with derivatives of the opium poppy. Thus, heroin addiction made its insidious way back to the forefront of national concern.20

Finally, disturbing reports about heroin abuse began to appear that focused not only on Americans at home but also on American armed forces personnel stationed in Vietnam. Reports beginning in the late 1960s indicated an increasingly widespread recreational abuse of heroin, along with alcohol, marijuana, and other drugs, among U.S. soldiers.

With respect to heroin, the problem was exacer- bated given that Vietnamese heroin was 90 to 98 per- cent pure, compared to 2 to 10 percent pure in the United States at the time, and incredibly cheap to buy. A 250-mg dose of heroin, for example, could be pur- chased for $10, whereas the standard intravenous dose on the streets of a major U.S. city would amount to only 10 mg. A comparable 250 mg of highly diluted U.S. heroin would have cost about $500. With the purity of heroin supplies so high, most U.S. soldiers smoked or sniffed it to get an effect; some drank it mixed with alcohol, even though most of the drug was lost as it was filtered through the liver en route to the bloodstream.21

Military involvement in Vietnam brought U.S. soldiers in con- tact with unusually potent doses of heroin and other psycho- active drugs.

126 ■ Part Two Legally Restricted Drugs in Our Society

In 1971, it was estimated from survey data that about 11 percent of American troops were regular users of heroin and about 22 percent had tried it at least once. Beyond the concern for the soldiers overseas, there was the considerable worry that at least one in ten Vietnam veterans would be returning home heroin-dependent and continuing a pattern of heroin abuse. As a response, the military instituted a mandatory program of urinalysis testing (appropriately named Operation Golden Flow), conducted near the end of a soldier’s tour of duty. In October 1971, three months of testing showed that about 5 percent of soldiers tested positive for heroin. The percentage of heroin abusers at that time could very well have been higher since there were strong indi- cations that soldiers had voluntarily given up heroin prior to their being shipped home.22 Fortunately, a comprehensive investigation in 1974 showed that only 1 to 2 percent of Vietnam veterans were regular heroin abusers one year following their return from overseas— approximately the same percentage as those entering the military from the general population.

Even if the original numbers of heroin abusers in Vietnam had been exaggerated in the first place (and evidence now suggests that the story was hyped out of proportion by the media at the time), the low number among returnees presents an interesting question. What happened to those who had been previously heroin abusers after they returned to the United States? It has been proposed that heroin use was specific to involve- ment in Vietnam. Once returning soldiers were home in the states, the stressful environmental cues and moti- vational factors for drug abuse were no longer present.23 Does that mean it is possible to abuse heroin with- out becoming dependent on it? This question will be addressed later in the chapter.

Heroin and Other Opioids Since the 1980s

At one time, the major source of white powder heroin smuggled into the United States was Turkey, where the opium was grown, and the center of heroin manufac- ture and distribution was Marseilles in southern France

(the infamous French connection, as popularized in the 1970 movie of the same name). International control over the growing of Turkish opium in 1973 closed this route of heroin distribution, but it succeeded only in encouraging other parts of the world to fill the vacuum. The “Golden Triangle” region of Laos, Myanmar (for- merly Burma), and Thailand became the principal play- ers in providing the United States with heroin. Joining southeast Asian heroin suppliers were southwest Asian nations such as Afghanistan, Pakistan, and Iran (in the “Golden Crescent”), as well as the central Asian nations of Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan that had been, until 1991, regions of the Soviet Union. As a consequence of these new sources, the purity of imported heroin at this time increased from around 5 percent to over 18 percent.24

Although the growth of crack cocaine abuse in the 1980s pushed the issue of heroin abuse temporar- ily off the front page, heroin abuse itself continued in new forms and variations. One significant development was the appearance around 1985 of a relatively pure and inexpensive form of Mexican heroin called black tar. In addition, new synthetic forms of heroin were appearing on the street, created in illegal drug laboratories within the United States. One such synthetic drug was derived from fentanyl, a prescription narcotic drug. Chemical modifications of fentanyl, anywhere from ten to a thou- sand times stronger than heroin, were sold under the common name “China White.” The risks of overdose death increased dramatically.

At that time, fentanyl derivatives and similar “designer drugs” were legal, owing to a loophole in the drug laws; because they were not chemically identical to heroin, no specific law applied to them. In 1986, the Controlled Substance Analogue Act closed this unfortu- nate loophole. The laws now state that any drug with a chemical structure or pharmacological effect similar to that of a controlled substance is as illegal as the genuine article. The mid-1990s witnessed still another shift in the pattern of heroin trafficking. The dominant source of white-powder heroin in the United States, judged from the analysis of drug seizures, was no longer Asia but South America, principally Colombia.

Street heroin from South American sources was now both cheaper and purer. Heroin purities exceeded 60 percent, at least ten times more powerful than the typical street heroin in the 1970s. In 1994, a 90-percent- pure brand of heroin circulating in New York City took heroin abusers by surprise; several overdose deaths occurred within a period of five days. Street prices for a milligram of heroin in New York fell from $1.81 in 1988 to as little as 37 cents in 1994. By government estimates,

black tar: A potent form of heroin, generally brownish in color, originating in Mexico.

fentanyl (Fen-teh-nil): A chemical derivative of thebaine, used as a prescription painkiller. The street name for fentanyl and related compounds is China White.

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 127

heroin consumption nationwide in 1996 had doubled from a decade earlier. As one writer put it, “If the U.S. auto industry cut the price of its sedans by half and rede- signed them to go 180 mph, no one would wonder why sales hit the roof.”25

In the mid-1990s, there was also a shift in the percep- tion of heroin abuse itself. As the popularity of cocaine abuse declined and the incidence of crack abuse began to ebb, the spotlight once more turned toward the allure of heroin. For a brief time, popular movies (Pulp Fiction in 1994, Trainspotting in 1995) and fashion photography (Calvin Klein fragrance advertisements in 1996) pre- sented provocative images that glamorized heroin abuse, a phenomenon the media dubbed “heroin chic.”

As the potency of heroin increased during the 1990s, a significant change occurred in the way heroin was abused. Due to the availability of increasingly pure her- oin, the drug no longer needed to be injected. Instead, it could be snorted (inhaled through the nose) or smoked. New heroin abusers were frequently smoking mixtures of heroin and crack cocaine or heating heroin and inhal- ing its vapors. These methods of heroin abuse avoided potential HIV infections or hepatitis through contami- nated needles, but they did not prevent the dependence that heroin could produce or the risk of heroin overdose.

Unfortunately, heroin snorting or smoking opened the door to new populations of potential heroin abusers who had previously stayed away from the drug because of their aversion to hypodermic needles. University of Michigan surveys from 1991 to 2011 indicate that 1 to 2 percent of all high school seniors reported heroin use at some time in their lives, with a majority of them smoking heroin rather than injecting it. However, the prevalence rate was not uniform across the United States in demographic or geographic terms. The incidence of heroin smoking among young people was and continued to be gener- ally higher than the national average and predominant in suburban communities, particularly in the Northeast.26

Although approximately 94 percent of the world’s supply of heroin today originates from the opium crop in Afghanistan, relatively little is destined for the United States. The major supplies of U.S. heroin come from opium grown in Colombia and Mexico. Mexico serves as the principal transport route for Colombian heroin (see Chapter 2). At present, Mexico is a major player in opium cultivation, second only to Afghanistan, as Colombian cultivation is on the decline. Whether this pattern of heroin trafficking continues remains to be seen. Illicit drug trafficking, in general, is in constant flux, subject to shifting market demands and the con- tinuing challenges posed by U.S. and international law enforcement agencies.27

Effects on the Mind and the Body

Recreational opioid use in the United States involves a range of drugs other than heroin itself, but we will concentrate on acute effects from the perspective of the heroin abuser. We have to be careful, however, to recognize that the specific effects are quite variable. The intensity of a response to heroin changes as a func- tion of (1) the quantity and purity of the heroin taken, (2)  the route through which heroin is administered, (3) the interval since the previous dose of heroin, and (4) the degree of tolerance of the user to heroin itself. In addition, there are psychological factors related to the setting, circumstances, and expectations of the user that make an important difference in what an individual feels after taking heroin.28 Nonetheless, there are sev- eral major effects that occur often enough to qualify as typical of the experience.

If heroin is injected intravenously, there is an almost immediate tingling sensation and sudden feeling of warmth in the lower abdomen, resembling a sexual orgasm, for the first minute or two. There is a feeling of intense euphoria, variously described as a “rush” or a “flash,” followed later by a state of tranquil drowsi- ness that heroin abusers often call being “on the nod.”

Understanding the History of Opium and Opioids Check your understanding of the historical background for opium and opioids by answering the following ques- tion. Imagine yourself to be living as a male adult in the year 1900. Check yes or no to indicate whether the fol- lowing psychoactive drugs would be available to you.

1. heroin yes no

2. opium yes no

3. fentanyl yes no

4. oxycodone yes no

5. morphine yes no

Answers: 1. yes 2. yes 3. no 4. no 5. yes

Quick Concept Check 5.1

128 ■ Part Two Legally Restricted Drugs in Our Society

During this period, which lasts from three to four hours, any interest in sex is greatly diminished. In the case of male heroin abusers, the decline in sexual desire is due, at least in part, to the fact that opiates reduce the lev- els of testosterone, the male sex hormone. Withdrawal symptoms can begin in about four hours. Therefore, maintaining a relatively constant “heroin high” often requires three or four administrations in a given day.29

Ironically, an individual’s first-time experience with heroin may be considerably unpleasant. Opiates in gen- eral cause nausea and vomiting, as the reflex centers in the medulla are suddenly stimulated. Some first-time abusers find the vomiting so aversive that they never try the drug again; others consider the discomfort largely irrelevant because the euphoria is so powerful.

There are a number of additional physiological changes in the body. A sudden release of histamine in the bloodstream produces an often intense itching over the entire body and a reddening of the eyes. Heroin also causes pupillary constriction, resulting in the charac- teristic “pinpoint pupils” that are used as an important diagnostic sign for narcotic abuse in general. Like sed- ative-hypnotic drugs (see Chapter 13), heroin reduces the sensitivity of respiratory centers in the medulla to levels of carbon dioxide, resulting in a depression in breathing. At high doses, respiratory depression is a major risk factor that can result in death. Blood pres- sure is also depressed from heroin intake. A suppression of the immune system over time increases the risk of infectious disease. Finally, a distressing, though nonle- thal, effect of heroin is the slowing down of the gastro- intestinal tract, causing labored defecation and intense constipation.30

How Opioids Work in the Brain

It is useful to view the neurochemical basis for a number of psychoactive drugs in terms of their influence on specific neurotransmitters in the brain. For example, the stimulant effects of cocaine and amphetamine are related to changes in norepinephrine and dopamine (see Chapter 4). In the case of opioid drugs, however, as a result of major discov- eries in the 1970s, it is clear that we are dealing with a more direct effect: the activation of receptors in the brain that are specifically sensitive to morphine.

During the 1960s, suspicions grew that a morphine- sensitive receptor, or a family of them, exists in the brain. One major clue came from the discovery that small chemical alterations in the morphine molecule would result in a group of new drugs with strange and intriguing properties. Not only would these drugs pro- duce little or no agonistic effects—that is, they would not act like morphine—but they would instead act as opiate antagonists—that is, they would reverse or block the effects of morphine (Figure 5.2).

The most complete opioid antagonist to be identi- fied, naloxone (brand name: Narcan), has turned out to have enormous therapeutic benefits in the emer- gency treatment of opioid-overdose patients. In such cases, intramuscular or intravenous injections of nal- oxone reverse the depressed breathing and blood pres- sure in a matter of a minute or so, an effect so fast that emergency-department specialists view the reaction as “miraculous.” The effect lasts for one to four hours. Higher doses of naloxone bring on symptoms that are similar to those observed following an abrupt with- drawal of opioids.

Interestingly, in nondrugged people, naloxone produces only negligible changes, either on a physiolog- ical or a psychological level. Only if morphine or other opioid drugs are already in the body does naloxone have an effect.31

Morphine

Naloxone

F i g u r e 5 . 2

Only minor differences exist between a morphine molecule and a naloxone molecule. Yet naloxone is a complete antagonist to morphine.

naloxone (nah-lOX-ohn): A pure antagonist for morphine and other opioid drugs. Brand name is Narcan.

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 129

Beyond its practical application, the discovery of naloxone had theoretical implications as well. The argu- ment went as follows: If such small molecular changes could so dramatically transform an agonist into an antagonist, then the drug must be acting on some recep- tor in the brain that can be easily excited or inhibited. The concept of a special morphine-sensitive receptor fulfilled these requirements.

The actual receptors themselves were discovered in 1973, precisely where you would have expected them to be: in the spinal cord and brain, where pain signals are known to be processed, and in the limbic system of the brain, where emotional behaviors are coordinated. In other words, it was clear that the analgesic and euphoric properties of morphine were due to the stimulation of these receptors.

Why would these receptors exist in the first place? No one seriously considers the possibility that receptors in the brain have been patiently waiting, during mil- lions of years of evolutionary history, for the day that the juice of the opium poppy could finally slip inside them! The only logical answer is that we must be producing our own morphine-like chemicals that activate these receptors.

As a result of a series of important discoveries from 1975 to the early 1980s, three groups of natural mor- phine-like molecules have been identified: enkephalins, beta-endorphins, and dynorphins. Together, they are known as endogenous opioid peptides, inasmuch as they are all (1) peptide molecules (amino acids strung together like a necklace), (2) opium-like in function (hence the word opioid), and (3) produced within the central nervous system. Unfortunately, this is such an unwieldy name that more frequently they are simply referred to as endorphins.

What can we then conclude about the effect of opi- ates on the brain? The answer, as we now understand it, is that the brain has the ability to produce its own “opi- oid” substances, called endorphins, and contains a spe- cial set of receptor sites to receive them. By an amazing quirk of fate, the opium poppy yields a similarly shaped chemical that fits into these receptor sites, thus produc- ing equivalent psychological and physiological effects. Naloxone acts as an opioid antagonist because its struc- tural features enable it to fit into these receptor sites, replacing the opioid molecules that have gotten in. The receptors themselves, however, are inactivated by nalox- one. This is why naloxone can “undo” the acute effects of an opioid drug like heroin.

A long-acting form of naloxone, naltrexone (brand name: ReVia, previously marketed as Trexan), adminis- tered orally three times per week, has since been found

to be a useful medication in the treatment of heroin abuse, mainly for patients who are highly motivated to stop their drug-taking behavior. Such patients include doctors, nurses, and other health professionals who must end a pattern of heroin abuse to retain their licenses and former heroin abusers on parole who are at risk of returning to prison if they suffer a relapse. Injectable slow-release formulations that extend the effects of nal- trexone over thirty days or more are presently being investigated, in an effort to free patients from having to rely on a more frequent oral administration sched- ule. A once-per-month slow-release form of naltrexone (brand name: Vivitrol) has been available for alcohol dependence since 2006 (see Chapter 9). In 2009, a combined naltrexone and extended-release morphine capsule (brand name: Embeda) was introduced to provide a morphine-induced analgesia while reduc- ing the possibility of abuse. The combination makes it impossible to crush and snort the capsules, because crushing releases the naltrexone and counteracts the morphine effect (see pages 137–139 on the problems of OxyContin abuse).32

Patterns of Heroin Abuse

The dominant route of administration in heroin abuse is intravenous injection, usually referred to as either mainlining or shooting. Heroin also can be admin- istered by a variety of other routes. Heroin smoking is popular in Middle Eastern countries and in Asia, but until very recently it has seldom been observed in the United States. Newcomers to heroin may begin their abuse either by snorting the drug through the nose or injecting it subcutaneously (skin-popping). Experienced heroin abusers may snort heroin to avoid using a needle or choose the subcutaneous route when they can no longer find veins in good enough condition to handle an intravenous injection. As mentioned earlier, an oral administration of heroin is usually worthless because absorption is extremely poor. American soldiers in Vietnam who were abusing heroin often took the drug orally, but because of the extremely high purity of the

endogenous opioid peptides (en-dOdge-eh-nus OH-pee-oid PeP-tides): Also known as endorphins. A class of chemicals produced inside the body that mimic the effects of opioid drugs.

naltrexone (nal-TreX-ohn): A long-lasting form of naloxone. Brand name prior to 1994 was Trexan; brand name has since been changed to ReVia.

130 ■ Part Two Legally Restricted Drugs in Our Society

heroin being consumed, their effective dose levels equaled or slightly exceeded levels found on American streets at the time.

Tolerance and Withdrawal Symptoms

A prime feature of chronic heroin abuse is the tolerance that develops, but the tolerance effects themselves do not occur in every bodily system. Gastrointestinal effects of constipation and spasms do not show much toler- ance at all, whereas distinctive pupillary responses (the pinpoint feature of the eyes) eventually subside with chronic use. The greatest signs of tolerance are seen in the degree of analgesia, euphoria, and respiratory depression. The intense thrill of the intravenous injec- tion will be noticeably lessened. The overall decline in heroin reactions, however, is dose-dependent. If the continuing dose level is high, then tolerance effects will be more dramatic than if the dose level is low.

The first sign of heroin withdrawal, a marked crav- ing for another fix, generally begins about four to six hours after the previous dose and intensifies gradually to a peak over the next thirty-six to seventy-two hours, with other symptoms beginning a few hours later (Table 5.1). The abuser is essentially over the withdrawal period in five to ten days, though mild physiological disturbances, chiefly elevations in blood pressure and heart rate, are observed as long as six months later. Generally, these long-term effects are associated with a gradual with- drawal from heroin rather than an abrupt one.

The overall severity of heroin-withdrawal symp- toms is a function of the dosage levels of heroin that have been sustained. When dosage levels are less than 10 percent, the withdrawal symptoms are comparable to a moderate to intense case of the flu. In more severe cases, the withdrawal process can result in a significant loss of weight and body fluids. With recent increases in the purities of street heroin in the 1990s, the symptoms of withdrawal are greater. Only rarely, however, is the process of heroin withdrawal life-threatening, unlike the withdrawal from barbiturate drugs (see Chapter 13).

It should not be surprising that withdrawal symp- toms are essentially the mirror image of symptoms observed when a person is under the influence of heroin. If we are dealing with a group of endorphin-sensitive receptors that are, in the case of the heroin abuser, being stimulated by the opioids coming in from the outside, then it is reasonable to assume that over time, the pro- duction of endorphins would decline. Why produce

something on your own when you are getting it from an external source? By that argument, withdrawal from her- oin would then be a matter of cutting off those receptors from that external source, resulting in a reaction oppo- site to the one that would have occurred had the recep- tors been satisfied in the first place. Over a period of time, coinciding with the withdrawal period for a heroin abuser, we would expect that the normal production of endorphins would reestablish itself and there would be little or no need for the external supply of heroin.

The receptor explanation for heroin dependence sounds reasonable and does account for the presence of withdrawal symptoms, but unfortunately it is an over- simplification for heroin abuse in general. We would expect that once the endorphin-sensitive receptors regain their natural supply of endorphins, heroin abuse should end, but we know that it does not.

In the case of heroin abusers, their tendency to con- tinue taking heroin is propelled by a number of factors. There is, first of all, the combination of fear and distress associated with the prospect of experiencing withdrawal symptoms, along with a genuine craving for the effects themselves, reflecting the physical and psychological dependence that heroin inflicts. In addition, long- term heroin abuse frequently produces such a power- ful conditioned-learning effect that the social setting in which the drug-taking behavior has occurred takes on reinforcing properties of its own (see Chapter 2). Even the act of inserting a needle can become pleasurable. Some heroin abusers (called needle freaks) continue to insert needles into their skin and experience heroin-like effects even when there is no heroin in the syringe. In effect, the heroin abuser is responding to a placebo. Any long-term treatment for heroin abuse, as will be discussed in a later section, must address a range of physical, psychological, and social factors to be successful.

The Lethality of Heroin Abuse

Considering the numbers of hospital emergencies and deaths associated with heroin abuse (see Chapter 2), you might be surprised that one would question the toxicity of heroin itself. To understand the toxicity of heroin, we first need to separate the effects of chronic heroin abuse from the drug’s acute effects. From a long-term perspective with regard to one’s physical health, heroin is considered relatively nontoxic, particularly when compared to sev- eral other drugs of abuse. Organ systems are not damaged or impaired by even a lifetime of heroin abuse, by virtue of ingesting the drug itself. There are no malformations, tissue damage, or physical deterioration directly tied to

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 131

the use of any opioid drug, including heroin.33 A notable exception, however, is found in the case of heroin admin- istered by inhaling the heated heroin vapors (sometimes referred to as “chasing the dragon”). This form of heroin abuse has been linked to leukoencephalopathy, a neuro- logical disease in which a progressive loss of muscle coor- dination can lead to paralysis and death.34

On the other hand, it is abundantly clear that the practice of heroin abuse is highly dangerous and poten- tially lethal. The reasons have to do with a number of situations resulting from heroin administration itself.35

■ Heroin has a relatively small ratio of LD (lethal dose) to ED (effective dose). Increase a dose that produces a high in a heroin abuser by ten or fifteen times, and you will be in the dosage range that is potentially fatal. As a result, death by overdose is an ever-present risk. If we take into account the virtually unknown potency of street heroin in any given fix, we can appreciate the hazards of a drug overdose. The “bag” sold to a heroin abuser may look like the same amount each time, but the actual heroin content may be anywhere from none at all to 90 percent. Therefore, it is easy to underestimate the amount of heroin being taken in.

■ Heroin abusers risk possible adverse effects from any toxic substance that has been “cut” with the heroin. Add- ing to the complexity, deaths from heroin overdose are frequently consequences of synergistic combinations of heroin with other abused drugs such as stimulants like cocaine or depressants like alcohol, Valium, or barbitu- rates. In some cases, individuals have smoked crack as their primary drug of abuse and snorted heroin to ease the agitation associated with crack. In other cases, lines of cocaine and heroin are alternately inhaled in a single session, a practice referred to as “criss-crossing.”

■ It is also possible that some heroin abusers develop unstable levels of tolerance that are tied to the environ- mental setting in which the heroin is administered. As a result of conditioned tolerance (see Chapter 2), a heroin dose experienced in an environment that has not been previously associated with drug taking may have a signif- icantly greater effect on the abuser than the same dose taken in more familiar surroundings. Consequently, the specific effect on the abuser is highly unpredictable.

■ Although the overriding danger of excessive amounts of heroin is the potentially lethal effect of respiratory depression, abusers can die from other physiologi- cal reactions. In some instances, death can come so quickly that the victims are found with a needle still in their veins; such deaths are usually due to a mas- sive release of histamine or to an allergic reaction to some filler in the heroin to which the abuser was

hypersensitive. Intravenous injections of heroin increase the risks of hepatitis or HIV infections, and unsterile water used in the mixing of heroin for these injections can be contaminated with bacteria.

■ An additional risk began to appear during the mid- 1980s. In some forms of synthetic heroin illicitly pro- duced in clandestine laboratories in the United States, “manufacturers” failed to remove an impurity called MPTP that destroys dopamine-sensitive neurons in the substantia nigra of the midbrain. As a result, young people exposed to this type of heroin could acquire full-blown symptoms of Parkinson’s disease (see Chap- ter 3) that were virtually identical to the symptoms observed in elderly patients suffering from a progres- sive loss of dopamine-sensitive neurons in their brains.

Quick Concept Check 5.2

Understanding the Effects of Administering and Withdrawing Heroin Without looking at Table 5.1, check your understanding of the effects of heroin, relative to withdrawal symptoms, by noting whether the following symptoms are associated with administering heroin or withdrawing it.

symptom administering withdrawing

1. twitching and sneezing

2. skin flushed and warm

3. decreased sex drive

4. yawning and panting

5. pain and irritability

6. pupillary constriction

7. increased blood pressure

8. diarrhea

9. analgesia

Answers: 1. withdrawing 2. administering 3. adminis- tering 4. withdrawing 5. withdrawing 6. administer- ing 7. withdrawing 8. withdrawing 9. administering

132 ■ Part Two Legally Restricted Drugs in Our Society

Heroin Abuse and Society

Over the years, society has had to deal with the reality of drug abuse in many forms, but many people still look upon heroin abuse as the ultimate drug addiction and view the heroin abuser as the ultimate “dope addict.” It is true that many heroin abusers fit this image: people driven to stay high on a four- to eight-hour schedule, committing a continuing series of predatory crimes. Yet the actual picture of the present-day heroin abuser is more complex. A major study has shown that although robbery, burglary, and shoplifting accounted for 44 per- cent of an abuser’s income and for nearly two-thirds of that abuser’s criminal income, a substantial amount of income came from either victimless crimes (such as pimping or prostitution) or noncriminal activity. Often a heroin abuser would work in some capacity in the underground drug industry and be paid in heroin instead of dollars.36

A related question with regard to our image of the heroin abuser is whether controlled heroin abuse is pos- sible. Is heroin abuse a situation that is, by definition, out of control? For most heroin abusers, the answer is yes. Yet for some individuals, heroin may not be a com- pulsion. The practice of controlled or paced heroin intake is referred to as chipping, and the occasional heroin abuser is known as a chipper. An important study conducted by Norman E. Zinberg in 1984 analyzed a group of people who had been using heroin on a con- trolled basis for more than four years.37 Over the course of one year, 23 percent reported taking heroin less than once a month, 36 percent reported taking it one to three times a month, and 41 percent reported taking it twice a week. Four years of exposure to heroin would seem to have been sufficient time to develop a compulsive dependence, but that did not happen. The observa- tion that most compulsive heroin-dependent individu- als never had any period of controlled use implies that controlled heroin abuse actually might not be an early transitional stage that eventually turns into uncontrolled heroin dependence.

Although the Zinberg findings have provided sup- port for the possibility of long-term heroin abuse on a controlled basis, newer evidence from studies of heroin abusers over more than three decades—a period of time

much longer than that studied by Zinberg—indicates a somewhat darker scenario. During the 1970s, 1980s, and 1990s, a series of follow-up investigations were car- ried out on nearly six hundred male heroin abusers who had been admitted to a compulsory drug-treatment program for heroin-dependent criminal offenders from 1962 to 1964. By 1996–1997, only 42 percent of individ- uals in the original sample, on average about fifty-eight years old at the time, were available for interview. About 9 percent were of unknown status, and 49 percent had died. The most common cause of death (22 percent) was accidental poisoning from heroin adulterants or her- oin overdose. Homicide, suicide, or accident accounted for 20 percent of the deaths, with the remainder being related to liver disease, cardiovascular disease, or can- cer. Regarding the drug-taking behavior of the survivors, the researchers concluded that heroin dependence had been very difficult for them to avoid. As the principal investigator of the study has expressed it,

Although many of the survivors reported that they had been able to stop using heroin for extensive periods, fewer than half reported abstinence for periods of more than five years. Abstinence for five years significantly reduced the likelihood of relapse, but even among those who achieved fif- teen years of abstinence, a quarter [of them] still relapsed.38

Moreover, large proportions of these men were engaged in alcohol, cocaine, or amphetamine abuse as well. The bottom line is this: Dabbling in a drug as potentially dependence-inducing as heroin is an extremely risky business. To paraphrase the words of a nationally prominent drug-abuse counselor, it is equivalent to playing a pharmacological form of Russian roulette.

Treatment for Heroin Abuse

For the heroin abuser seeking treatment for heroin dependence, the two primary difficulties are the short- term effects of heroin withdrawal and the long-term effects of heroin craving. Any successful treatment, therefore, must combine a short-term and a long-term solution.

Heroin Detoxification Traditionally, it has been possible to make the pro- cess of withdrawal from heroin, called detoxification (“detox”), less distressing to the abuser by reducing

chipping: The taking of heroin on an occasional basis.

detoxification: The process of drug withdrawal in which the body is allowed to rid itself of the chemical effects of the drug in the bloodstream.

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 133

the level of heroin in a gradual fashion under medi- cal supervision, rather than withdrawing from heroin “cold turkey” (a term inspired by the gooseflesh appear- ance of the abuser’s skin during abrupt withdrawal). In medical settings, opioid drugs such as propoxyphene (brand name: Darvon), meperidine (brand name: Demerol), or methadone are administered orally to replace the heroin initially; then doses of these so- called transitional drugs are decreased over a period of two weeks or so.39

Methadone Maintenance For the heroin abuser seeking out medical treatment for heroin dependence, the most immediate problem is get- ting the drug out of the abuser’s system during detoxi- fication with a minimum of discomfort and distress. In some procedures, the administration of naloxone has been used to speed up withdrawal and reduce the sever- ity of physiological symptoms.

After detoxification, however, the long-term prob- lem of drug dependence remains. The craving for heroin persists, and the abuser most often has little choice but to return to a drug-oriented environment where the temptations to satisfy the craving still exist. Since the mid-1960s, one strategy has been to have a detoxified heroin abuser participate in a program in which oral administrations of the methadone are essen- tially substituted for the injected heroin. This treat- ment approach, called methadone maintenance, was initiated in New York City through the joint efforts of Vincent Dole, a specialist in metabolic disorders, and Marie Nyswander, a psychiatrist whose interest had focused on narcotic dependence. Their idea was that if a legally and carefully controlled opioid drug was avail- able to heroin abusers on a regular basis, the craving for heroin would be eliminated, their drug-taking lifestyle would no longer be needed, and they could turn to more appropriate social behaviors such as steady employment and a more stable family life. The general philosophy behind this approach to heroin-abuse treatment was that heroin abuse was essentially a chronic metabolic dis- order requiring a long-term maintenance drug for the body to “normalize” the drug abuser, in the same way as a diabetic patient would need a maintenance supply of insulin.

There are several advantages of the methadone maintenance approach in heroin-abuse treatment. Since it is a legal, inexpensive narcotic drug (when dispensed through authorized drug-treatment cen- ters), criminal activity involved in the purchase of heroin on the street can be avoided. Methadone is

slower acting and more slowly metabolized, so that, unlike heroin, its effects last approximately twenty- four hours and it can be easily absorbed through an oral administration. Because it is an opioid drug, methadone binds to the endorphin-sensitive recep- tors in the brain (Chapter 3) and prevents feelings of heroin craving, yet the rush of a heroin high is avoided, thanks to its relatively slow rate of absorption by brain tissue.

Typically, clients in the program come to the treatment center daily for an oral dose of methadone, dispensed in orange juice, and the dose is gradually increased to a maintenance level over a period of four to six weeks. The chances of an abuser turning away from illicit drug use are increased if the higher doses of methadone are made conditional on a “clean” (drug- free) urinalysis.40

As a social experiment, methadone-maintenance programs have met with a mixture of success and fail- ure. On the one hand, evaluations of this program have found that 71 percent of former heroin abus- ers who have stayed in methadone maintenance for a year or more have stopped intravenous drug tak- ing, thus reducing the risk of AIDS. In a major study, drug-associated problems declined from about 80 per- cent to between 17 and 28 percent, criminal behav- ior dropped from more than 20 percent to less than 10 percent, and there was a slight increase in perma- nent employment.41 Although it attracts only a frac- tion of the heroin-dependent community, methadone maintenance does attract those who perceive them- selves as having a negligible chance of becoming abstinent on their own.42

Although opioid maintenance programs do help many heroin abusers, particularly those who stay in the program over an extended period of time, there are strong indications that the programs do not reduce the overall vulnerability to drug abuse in general. In other words, methadone blocks the yearn- ing for heroin, but it is less effective in blocking the simple craving to get high. Alcohol abuse among methadone-maintenance clients, for example, ranges

propoxyphene (pro-POX-ee-feen): A synthetic (laboratory-based) opioid useful in reducing pain. Brand names are Darvon, Darvocet.

methadone: A synthetic (laboratory-based) opioid useful in treating heroin abuse.

methadone maintenance: A treatment program for heroin abusers in which heroin is replaced by the long-term intake of methadone.

134 ■ Part Two Legally Restricted Drugs in Our Society

from 10 percent to 40 percent, suggesting that alco- hol may be substituting for opioids during the course of treatment, and one study found that as many as 43 percent of those who had successfully given up heroin had become dependent on alcohol. 43 Furthermore, methadone is sometimes diverted away from the clinics and onto the streets for illicit use. The availability of street methadone remains a mat- ter of great concern.44

Alternative Maintenance Programs Two alternative orally administered maintenance drugs for heroin abusers have been developed that avoid the problems associated with the daily dosage approach of methadone programs. The first is the opioid LAAM (levo-alpha-acetylmethadol), marketed under the brand name Orlaam. The advantage of LAAM is its substan- tially longer duration, relative to methadone, so that treatment clients need to receive the drug only three times a week instead of every day.45

The second drug is the opioid buprenorphine (brand name: Subutex), also available as a three-times- a-week medication. Both medications have been shown to be useful in treating heroin abuse. To reduce the potential for buprenorphine tablets to be made into an injectable form and abused, buprenorphine is also available in combination with naloxone (brand name: Suboxone). If the tablets are crushed and dissolved into an injectable solution, the combined formulation trig- gers undesirable withdrawal symptoms.

The advantage of buprenorphine as a heroin-abuse treatment is that it can be prescribed by office-based physicians rather than having to be dispensed through maintenance centers, as is the case with methadone and LAAM. When it is combined with naloxone, the abuse potential of buprenorphine is minimized, and while

long-term blockage of opioid receptors occurs, there is less of an opioid “high.” Buprenorphine treatment substantially reduces the cost to public health clin- ics because it can be administered more widely in less heavily secured medical locations, such as primary-care clinics and physicians’ offices. It also reduces the incon- venience and stigmatization faced by treatment clients, particularly for teenage heroin abusers who would be disinclined to seek treatment at facilities that are asso- ciated with older people. Continuing advances in the forms of buprenorphine administration have made this option increasingly attractive as a heroin-abuse treat- ment. (Health Alert).46

Behavioral and Social-Community Programs To help deal with the tremendous social stresses that reinforce a continuation of heroin abuse as well as substance abuse in general, programs called thera- peutic communities (TCs) have been developed (examples include Daytop Village, Samaritan Village, and Phoenix House). These “mini-communities” are drug-free residential settings based on the idea that stages of treatment and recovery should reflect increased levels of personal and social responsibility on the part of the abuser. Peer influence, mediated through a variety of group processes, is used to help individuals learn and assimilate social norms and develop more effective social skills. Typically, coun- selors are former heroin abusers or former abusers of other drugs.47

Other approaches have been developed that combine detoxification, treatment with naltrexone, psychotherapy, and vocational rehabilitation under a single comprehensive plan of action. These pro- grams, called multimodality programs, are designed to focus simultaneously on the multitude of needs facing the heroin abuser, the goal being a success- ful reintegration into society. As a continuing effort to help the recovering heroin abuser over time, there are also twelve-step group support programs such as Narcotics Anonymous, modeled after similar pro- grams for those recovering from alcohol or cocaine dependence.

Medical Uses of Opioid Drugs

The focus in this chapter has been on the acute effects of opioid drugs in the context of heroin abuse, but it is also important to look at the beneficial

lAAm: The synthetic narcotic drug levo-alpha- acetylmethadol, used in the treatment of heroin abuse. Brand name is Orlaam.

buprenorphine (bYOO-preh-nOr-feen): A synthetic (laboratory-based) opioid used in the treatment of heroin abuse. Brand names are Subutex and (in combination with naloxone) Suboxone.

therapeutic communities: Living environments for individuals in treatment for heroin and other drug abuse, where they learn social and psychological skills needed to lead a drug-free life.

multimodality programs: Treatment programs in which a combination of detoxification, psychotherapy, and group support is implemented.

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 135

effects that these drugs can have in a medical setting (Table 5.2).

Beneficial Effects Excluding heroin, which is a Schedule I controlled substance in the United States and therefore unavail- able even for medical use, opioid drugs are available as prescription medications (Schedule II controlled substances) for three primary therapeutic purposes: the relief of pain, the treatment of acute diarrhea, and the suppression of coughing.

■ The first and foremost medical use of opioids today is for the treatment of pain. For a patient suffering severe pain following surgical procedures or from burns or cancer, the traditional drug of choice has been mor- phine. Recently, pain treatment with fentanyl through

a transdermal patch administration (see Chapter 3) has been found to be more effective as an analgesic than morphine in an oral time-release administration and is preferred by patients with chronic pain because the pain relief is achieved with less constipation and an enhanced quality of life. A transdermal buprenor- phine patch (brand name: Butrans) has recently become available as well.48

■ The second application capitalizes on the effect of opioids in slowing down peristaltic contractions in the intestines that occur as part of the digestive pro- cess. As noted earlier, one problem associated with the chronic abuse of heroin, as well as of other opi- oids, is constipation. However, for individuals with dysentery, a bacterial infection of the lower intestinal tract causing pain and severe diarrhea, this negative side effect becomes desirable. Therefore, the control of diarrhea by an opioid is literally life-saving, since

H e A l T H A l e r T !

sustained-release buprenorphine: A new era in Heroin-Abuse Treatment When buprenorphine (brand name: Subutex) and its combination with naloxone (brand name: Suboxone) received FDA approval in 2002, a new era of heroin-abuse treatment began. Because buprenorphine is only a par- tial activator of opioid-sensitive receptors in the brain, as opposed to full activators such as heroin and methadone, clients in treatment are more likely to discontinue their heroin intake without experiencing withdrawal symp- toms, and the symptoms that do occur are considerably milder. At the same time, buprenorphine administration avoids the typical heroin effects of euphoria and respira- tory depression. There is also no evidence of significant impairment of cognitive or motor performance in the course of long-term buprenorphine maintenance.

In recent years, significant developments have increased the convenience of buprenorphine adminis- tration as a heroin-abuse treatment. A sustained-release version of buprenorphine, administered by injection by a certified primary-care physician has made it possible for heroin abusers to obtain treatment only once per month and has lessened the potential for diversion. Federal leg- islation enacted in 2007 allows a certified physician to treat a caseload of up to one hundred patients. Previous regulations had limited caseloads to no more than thirty

patients. Additionally, a buprenorphine transdermal patch (brand name: Butrans), delivering 5-20 micrograms of buprenorphine hourly over a seven-day period, has been available since 2011 for heroin abuse treatment on an “off-label basis” (see Chapter 14).

Where to go for assistance: www.buprenorphine.samhsa.gov/about.html

This web site, sponsored by the Substance Abuse and Mental Health Services Administration of the U.S. Department of Health and Human Services, provides extensive information on treatment options and a list of available buprenorphine treatment locations. There are more than eight hundred physicians certified for buprenorphine treatment in New York State alone.

Sources: Martin, K. R. (2004, September). Once-a-month medication for heroin addiction? NIDA Notes, p. 9. Mitka, M. (2003). Office-based primary care physicians called on to treat the “new” addict. Journal of the American Medi- cal Association, 290, 735–738. Opioid detox study shows buprenorphine improves retention rate for teens (2005, October 10). Alcoholism and Drug Abuse Weekly, pp. 1–2. Purdue Pharma (2011, January 21). Butans transdermal system CIII now available. News and media release. Sub- stance Abuse and Mental Health Services Administration (2007, January/ February). Buprenorphine: Patient limits increase. SAMHSA Report, p. 7.

136 ■ Part Two Legally Restricted Drugs in Our Society

acute dehydration (loss of water from the body) can be fatal. Fortunately, the opioid medication loper- amide (brand name: Imodium), which is available on an over-the-counter basis, effectively controls diarrhea symptoms by its action on the gastrointestinal system.

Because it cannot cross the blood–brain barrier, loper- amide does not produce any psychoactive effects.

■ The third application focuses on the capacity of these drugs to suppress the cough reflex center in the medulla. In cases in which an antitussive (cough- suppressing) drug is necessary, codeine is frequently prescribed, either by itself or combined with other medications such as aspirin or acet aminophen (brand name: Tylenol, among others). As an alter- native treatment for coughing, a nonopiate drug, dextromethorphan, is available in over-the-counter syrups and lozenges, as well as in combination with

TAble 5.2

Major opioid pain medications

generiC nAme

brAnd nAme*

reCOmmended dOse FOr AdulTs

generiC nAme

brAnd nAme*

reCOmmended dOse FOr AdulTs

morphine Avinza 30–120 mg (oral, com- bined immediate release, and extended-release)

hydrocodone Hycodan

Vicodin

5 mg (oral)

5 mg (oral) with acetaminophen

Duramorph 5–10 mg (i.v.) methadone Dolophine 5–10 mg (oral, i.v., or s.c.)

Kadian 10–200 mg (oral, extended-release)

meperidine Demerol 50–100 mg (oral, i.m., i.v.)

MS Contin 15–200 mg (oral, controlled-release)

propoxyphene Darvocet-N 50 mg (oral) with acetaminophen

Oramorph SR 15–100 mg (oral, sustained-release) fentanyl

tramadol

Darvon

Duragesic

Actiq

Ultram ER

65 mg (oral)

12.5–100 mcg/hour (extended-release transdermal patch)

200–1,600 mcg (“lollipop” form),

100–300 mg (oral, extended-release)

Embeda 20–100 mg morphine/ 0.8–4 mg naltrexone (oral, sustained-release)

codeine 30–60 mg (oral, i.m., or s.c.)

hydromorphone

oxymorphone

Dilaudid

Numorphone

Opana IR

Opana ER

1–8 mg (oral, i.m., i.v., or s.c.)

Suppository, injectable

5-10 mg (oral, immediate release)

5-40 mg (oral, extended release)

oxycodone OxyContin 10–80 mg (oral, controlled-release)

Percocet 2.5–10 mg (oral) with acetaminophen

Percodan 4.5 mg (oral) with aspirin

*Two forms of buprenorphine are described in Health Alert on page 135). Some opioid drugs are available only under their ge- neric names, and some are available under either their generic or their brand names.

Note: i.v. = intravenous; i.m. = intramuscular; s.c. = subcutaneous.

Source: Physicians’ desk reference (67th ed.) (2013). Montvale, NJ: PDR Network.

antitussive: Having an effect that controls coughing.

dextromethorphan (deX-troh-meh-THOr-fan): A popular non-narcotic ingredient used in over-the- counter cough remedies. The “DM” designation on these preparations refers to dextromethorphan.

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 137

antihistamines. Unfortunately, the abuse of dextro- methorphan among young people, who are consum- ing it on a recreational basis, has become a relatively new cause for concern (see Chapter 1).

Prescription Pain Medication Misuse and Abuse

Even though the overall effects of prescription pain medications are beneficial, a number of serious prob- lems should be noted in the context of their legitimate medical use. For example, respiration will be depressed for four to five hours following even a therapeutic dose of morphine, so caution is advised when the patient suffers from asthma, emphysema, or pulmonary heart disease. In addition, opioid medications decrease the secretion of hydrochloric acid in the stomach and reduce the pushing of food through the intestines, a condition that can lead to intestinal spasms. Finally, although opioids have a sleep-inducing effect in high doses, it is not recommended that they be used as a gen- eral sedative-hypnotic treatment, unless sleep is being prevented by pain or coughing.49

Most importantly, however, is the widespread abuse of opioid medications in which the drugs are used for clearly nonmedical purposes. Medications that have been particularly problematic are the controlled- release form of oxycodone (brand name: OxyContin), hydrocodone with acetaminophen (brand name: Vicodin), oxycodone with acetaminophen (brand name: Percocet), and oxymorphone (brand name: Opana). All of these medications are classified in the United States as Schedule II controlled substances, according to the Controlled Substances Act of 1970.

OxyContin Abuse Introduced in 1995, OxyContin was promoted ini- tially as being relatively safe from potential abuse and more acceptable to the general public because it lacked the social stigma associated with morphine. Its FDA-approved formulation allows OxyContin to be taken orally and absorbed slowly over a period of twelve hours, killing pain without inducing a sudden feeling of euphoria. However, when OxyContin tab- lets are crushed and then either swallowed or inhaled as a powder, or injected after diluting the powder into a solution, the effect is similar to that of heroin. Even without altering the tablets in any way, some patients have suffered severe withdrawal symptoms, similar to those experienced during heroin withdrawal, when

they abruptly stopped taking high-dosage levels of the OxyContin.

Unlike heroin abusers, the demographic features of OxyContin abusers cut across age, socioeconomic status, geographic location, and gender. However, as is the case with methamphetamine (see Chapter 4), communities particularly hard-hit by this form of substance abuse have been located in small towns and rural areas. Driven by widespread opioid prescription drug abuse, twenty U.S. states reported in 2007 that the number of unintentional overdose deaths exceeded deaths to either motor vehicle crashes or suicides, Nationwide, treatment facility admis- sions in 2008 increased more than threefold, relative to 1998, among abusers aged 18 to 34 years. With many regions lacking the necessary funds for adequate systems to monitor pharmacy sales, abusers have been able to obtain multiple prescriptions for OxyContin and similar medications through the practice of “doctor shopping.” Pharmacy robberies, when prescription access fails, are on the rise (see Portrait on page 138).50

Responses to OxyContin Abuse Efforts have been made to reduce OxyContin abuse in a number of ways. An FDA-mandated warning label now states that the drug is as potentially addictive as morphine and that chewing, snorting, or injecting it could be lethal. In 2010, Purdue Pharma, manufacturer of OxyContin, introduced a new formulation (brand name: OxyNeo) containing an added chemical called Remoxy that changed the tablet into a gummy, less eas- ily abusable substance when crushed or dissolved.

Unfortunately, alternative means have been found in an attempt to circumvent these changes. Some abus- ers have turned to microwaving the new formulation and sniffing the burned remains, a far less convenient but nonetheless viable option.51 Others have turned to the extended-release form of another opioid medica- tion, oxymorphone (brand name: Opana ER), which can be crushed and dissolved like the original form of OxyContin. In 2012, a new formulation of Opana ER was launched with a modification similar to that implemented with OxyContin, but whether these developments will sig- nificantly reduce the abuse of these medications remains to be seen. Clearly, it is extremely difficult to meet the public-health challenge in making effective pain medi- cations available for legitimate reasons and, at the same time, restricting the opportunities for abuse.52

OxyContin: A controlled-release form of oxycodone, used in the treatment of chronic pain.

138 ■ Part Two Legally Restricted Drugs in Our Society

Abuse of Other Opioid Pain Medications Vicodin and Percocet are based on opioids (hydroco- done and oxycodone, respectively) that have been avail- able for a longer period of time, and they unfortunately have a longer record of abuse and dependence. An addi- tional problem has been the addition of acetaminophen (up to 1000 mg in the case of one form of Percocet) to the hydrocodone and oxycodone in these medications. This combination is particularly dangerous because excessive dosages of acetaminophen increase the risk of liver toxicity and death (see Chapter 14). In order to reduce the incidence of adverse effects, the FDA ordered in 2011 a limit of 325 mg of acetaminophen when combined with a prescription pain medication.53

Prevalence of Nonmedical Use of Opioid Pain Medications The nonmedical use of opioid pain medications has increased dramatically in recent years. It has been esti- mated that in 2011, approximately 7.6 million young adults aged eighteen to twenty-five (about 22 percent of individuals in this age group) reported to have used an opioid pain medication for nonmedical reasons in their lifetime. Approximately 2.1 million (6 percent) had used OxyContin, 5.5 million (16 percent) had used Vicodin, and 3.1 million (9 percent) had used Percocet for non- medical reasons in their lifetime. In 2009, prescription pain medications were responsible for approximately 15,000 deaths in the United States, exceeding the num- ber of deaths due to the overdose of cocaine or heroin.

P O r T r A i T David Laffer—Pharmacy Robber and Killer of Four

Arguably the most famous bank robber in American his- tory, Willie Sutton, was once asked by a reporter in an interview why, over a 40-year criminal career, he robbed banks. “Because that’s where the money is,” he explained. It’s become a famous quote, and prob- ably the most well-known quote by a lifelong criminal.

Today, it’s not the banks that are being robbed but the local pharma- cies. Why pharmacies? To update Willie Sutton’s explanation: “Because that’s where the drugs are.” To be more specific: “That’s where the OxyContin is.” From a law enforce- ment standpoint, pharmacy robberies have gotten totally out of control, in practically every region in America, in states as disparate as Oklahoma, Ohio, California, and Oregon. The Drug Enforcement Administration (DEA) reported more than 700 drug- related pharmacy robberies in 2012. And it has gotten deadly. In 2011, four people were killed during a suburban pharmacy robbery on Long Island, New York. The killer, David Laffer, had acquired nearly 12,000 opioid pain medication pills in the four years leading to the robbery.

From a street sale alone, the 80 mg dosage of OxyContin

has become a prime target for theft. A single pill at this dosage goes for $80 on the street, so a heist of even a few bottles can add up to real money. Meanwhile, pharmacists have had to contend with some difficult choices. Do they suspend all sales of Oxy- Contin, depriving the many patients with genuine pain-control issues? Do they institute security measures such as banks do? Do they hire guards around the clock to protect themselves?

Some pharmacies (particularly those that are independently owned) have upgraded their surveillance cameras, installed bulletproof glass- enclosed counters, and buzzers at the door for customers. Time-release locks on the safes used to store narcotics are now in place to reduce the number of burglaries. In one counter-move, a pharmacist in Maine took to attach- ing a tracking device on specific bottles of OxyContin, reserved for a potential pharmacy robber, that has led successfully to the location of the perpetrator. Some pharmacists have greatly restricted their stock supplies of oxycodone or OxyContin products

and have no regrets in telling this to their customers.

Several U.S. states are increasing the minimum jail time for second- degree robbery, when a pharmacist may be threatened but no weapon is shown (a typical scenario in phar- macy robberies), from three months to three years. As a county prosecu- tor in Washington State has put it, “Word travels fast on the street about what an easy target the pharmacies are and how much profit can be made and what small punishment is attached.”

Whatever the course that pharma- cies and law-enforcement agencies take, the crisis in prescription drug abuse is bound to continue. It is dif- ficult to battle an increasing trend in the quantity of opioid pain prescrip- tions that is being reported throughout the nation.

Sources: Goodnough, A. (2011, Febru- ary 7). Pharmacies under siege from robbers seeking drugs. New York Times, p. A14. Peddie, S.; Van Sant, W.; and Lewis, R. (2012, January 8). The fear in the pharmacies. Newsday, pp. A3, A4. Brown, J. (2011, June 23). The oxyco- done curse. Newsday, p. A8.

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 139

Nonmedical use of prescription pain medications is also extensive in high schools, though prevalence rates in 2011 were lower than peak level years in 2009. According to the University of Michigan survey, 8 percent of high school seniors in 2011 reported nonmedical use of

Vicodin (the most widely used opioid pain medication among this population) during the previous year. The decline in rates of Vicodin abuse may be a reflection of the current media coverage regarding the hazards of opioid pain-medication abuse in general.54

Summary

Opium in History ● A drug with a very long history, opium has been used

for medicinal and recreational purposes for approxi- mately 5,000 years.

● During the nineteenth century, opium figured in global politics as the instigating factor for the Opium War fought between China and Britain. At the time, opium use was widespread in Britain and the United States at all levels of society.

morphine and the Advent of Heroin ● The discovery of morphine in 1803 as the principal

active ingredient in opium revolutionized medical treatment of pain and chronic diseases.

● At the end of the nineteenth century, heroin was intro- duced by the Bayer Company in Germany. Initially, it was believed that heroin lacked the dependence- producing properties of morphine.

Opioids in American society ● The abuse potential of morphine and especially of

heroin was not fully realized until the beginning of the twentieth century. Social and political develop- ments in the United States after the passage of the Harrison Act in 1914 drove heroin underground, where it acquired a growing association with crimi- nal life.

● Heroin abuse became associated with African Ameri- can and other minority communities in urban ghet- tos after World War II; later, the drug revolution and the military involvement in Vietnam during the 1960s and 1970s brought the issue of heroin abuse to a wider population.

effects on the mind and the body ● The effects of opioids such as heroin include eupho-

ria, analgesia, gastrointestinal slowing, and respiratory depression.

● Respiratory depression is the major risk factor for her- oin intake.

How Opioids Work in the brain ● Since the 1970s, we have known that the effects of

morphine and related opioid drugs are the result of the activation of opioid-sensitive receptors in the brain.

● Three families of chemical substances produced by the brain bind to these receptors. These chemicals are collectively known as endorphins.

Patterns of Heroin Abuse ● Chronic heroin abuse is subject to tolerance effects

over time. Withdrawal effects include intense craving for heroin and physical symptoms such as diarrhea and dehydration.

● One of the major problems surrounding heroin abuse is the unpredictable content of a heroin dose.

Treatment for Heroin Abuse ● Treatment for heroin abuse includes short-term

detoxification and long-term interventions that address the continuing craving for the drug and physical dependence factors in the body.

● Methadone-maintenance programs focus primarily on the physiological needs of the heroin abuser, whereas therapeutic communities and support groups focus on his or her long-term reintegration into society.

Opioid use, misuse, and Abuse ● In medical settings, narcotic drugs have been

extremely helpful in the treatment of pain, in the treat- ment of dysentery, and in the suppression of coughing.

● Side effects of opioid medications include respiratory depression, intestinal spasms, and sedation.

● There has been great concern since the late 1990s that opioid pain medications have been diverted to nonmedical purposes and are subject to abuse. Three medications of this type are OxyContin, Vicodin, and Percocet. There are increasing reports of pharmacy robberies, with the intent of securing supplies of opioid pain medication, particularly OxyContin.

140 ■ Part Two Legally Restricted Drugs in Our Society

Key Terms

antitussive, p. 136 black tar, p. 126 buprenorphine, p. 134 chipping, p. 132 codeine, p. 123 detoxification, p. 132 dextromethorphan,

p. 136

endogenous opioid peptides, p. 129

fentanyl, p. 126 heroin, p. 124 LAAM, p. 134 methadone, p. 133 methadone maintenance,

p. 133

morphine, p. 123 multimodality programs,

p. 134 naloxone, p. 128 naltrexone, p. 129 narcotics, p. 119 opioids, p. 119 opium, p. 119

OxyContin, p. 137 propoxyphene, p. 133 thebaine, p. 123 therapeutic communities,

p. 134

1. Adapted from a composite of anonymous contributors to the Sober Living by the Sea blog, www.soberliving.com/ blog.

2. Levinthal, C. F. (1988). Messengers of paradise: Opiates and the brain. New York: Anchor Press/ Doubleday, p. 4.

3. Courtwright, D. T. (2001). Forces of habit: Drugs and the making of the modern world. Cambridge, MA: Harvard University Press, pp. 31–39. Merlin, M. D. (1984). On the trail of the ancient opium poppy. Cranbury, NJ: Associated University Press.

4. Scott, J. M. (1969). The white poppy: A history of opium. New York: Funk and Wagnalls, p. 111.

5. Nencini, P. (1997). The rules of drug-taking: Wine and poppy derivatives in the ancient world. VIII. Lack of evidence of opium addiction. Substance Use and Misuse, 32, 1581–1586.

6. Levinthal, Messengers of paradise, pp. 3–25. Snyder, S. H. (1977). Opiate receptors and internal opiates. Scientific American, 236 (3), 44.

7. Beeching, J. (1975). The Chinese opium wars. New York: Harcourt Brace Jovanovich, p. 23. Hanes, W. Travis III, and Sanello, F. (2002). The opium wars. Napierville, IL: Sourcebooks.

8. Owen, D. E. (1934). British opium policy in China and India. New Haven, CT: Yale University Press. Waley, A. (1958). The opium war through Chinese eyes. London: Allen and Unwin.

9. DeQuincey, T. (1822/2002). Confessions of an English opium-eater. In D. F. Musto (Ed.), Drugs in America: A documentary history. New York: New York University, pp. 197–199. Fay, P. W. (1975). The opium war 1840– 1842. Chapel Hill: University of North Carolina Press, p. 11.

10. Brecher, E. M., and the editors of Consumer Reports (1972). Licit and illicit drugs. Boston: Little, Brown, p. 17.

11. Kaplan, E. H., and Wieder, H. (1974). Drugs don’t take people; people take drugs. Secaucus, NJ: Lyle Stuart.

12. Brecher, Licit and illicit drugs, pp. 42–43. 13. Levinthal, Messengers of paradise, pp. 16–17.

14. Courtwright, D. T. (1982). Dark paradise: Opiate addic- tion in America before 1940. Cambridge, MA: Harvard University Press, p. 47.

15. Inciardi, J. A. (2002). The war on drugs III. Boston: Allyn and Bacon, p. 24. Terry, C. E., and Pellens, M. (1928/1970). The opium problem. Montclair, NJ: Patterson Smith.

16. Substance Abuse and Mental Health Services Adminis- tration (2012). Results from the 2011 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Adminis- tration, Table 1.1A.

17. Smith, R. (1966). Status politics and the image of the addict. Issues in Criminology, 2 (2), 157–175.

18. Zackon, F. (1986). Heroin: The street narcotic. New York: Chelsea House Publishers, p. 44.

19. McCoy, A. W.; with Read, C. B., and Adams, L. P. (1972). The politics of heroin in southeast Asia. New York: Harper & Row, pp. 5–6.

20. Zackon, Heroin, p. 45. 21. Bentel, D. J.; Crim, D.; and Smith, D. E. (1972). Drug

abuse in combat: The crisis of drugs and addiction among American troops in Vietnam. In D. E. Smith and G. R. Gay (Eds.), It’s so good, don’t even try it once: Her- oin in perspective. Englewood Cliffs, NJ: Prentice-Hall, p. 58.

22. McCoy, The politics of heroin, pp. 220–221. 23. Kuzmarov, J. (2010). The myth of the addicted army:

Vietnam and the modern war on drugs. Amherst, MA: University of Massachusetts Press. Robins, L. N.; David, D. H.; and Goodwin, D. W. (1974). Drug use by U.S. Army enlisted men in Vietnam: A follow-up on their return home. American Journal of Epidemiology, 99 (4), 235–249.

24. Greenhouse, S. (1995, February 12). Heroin from Burmese surges as U.S. debates strategy. New York Times, p. 3.

25. Holloway, L. (1994, August 31). 13 heroin deaths spark wide police investigation. New York Times, pp. A1, B2.

Endnotes

Chapter 5 Opioids: Opium, Heroin, and Opioid Pain Medications ■ 141

Leland, J. (1996, August 26). The fear of heroin is shoot- ing up. Newsweek, pp. 55–56. Quotation on p. 56.

26. Herbert, K. (2010, January 3). Deadly drug’s toll in black and white. Newsday, pp. A5–A6. Hernandez, D. (2003, May 23). Heroin’s new generation: Young, white, and middle class. New York Times, p. 34. Johnston, L. D.; O’Malley, P.M.; Bachman, J. G.; and Schulenberg, J. E. (2012). Monitoring the Future: National survey results on drug use, 1975–2011. Vol. I: Secondary school students, 2011. Ann Arbor, MI: Institute for Social Research, The University of Michigan. Table 2-1.Jones, R.G. (2008, January 13). Heroin’s hold on the young. New York Times, Long Island section, pp. 1, 8. Richey, Warren (1996, October 25). Boycott groups: Klein ads carry scent of “heroin chic.” Christian Science Monitor, p. 3.

27. National Drug Intelligence Center (2011). National Drug Threat Assessment 2011. Washington, DC: U.S. Department of Justice, pp. 26–28.

28. Winger, G.; Hofmann, F. G.; and Woods, J. H. (1992). A handbook on drug and alcohol abuse: The biomedi- cal aspects. New York: Oxford University Press, 1992, pp. 44–46.

29. Abel, E. L. (1985). Psychoactive drugs and sex. New York: Plenum Press, pp. 175–204.

30. McHugh, P. F., and Kreek, M. J. (2008). The medical consequences of opiate abuse and addiction and metha- done pharmacotherapy. In J. Brick (Ed.), Handbook of the medical consequences of alcohol and drug abuse, 2nd ed. New York: Routledge, pp. 303–339. Winger, Hof- mann, and Woods, Handbook on drug and alcohol abuse, pp. 46–50.

31. Julien, R. M. (2005), A primer of drug action (10th ed.). New York: Worth, pp. 490–492. Yaksh, T. L., and Wallace, M. S. (2012). In L. L. Brunton, B. A. Chabner, and B. C. Knollman (Eds.), Goodman and Gilman’s The pharmacological basis of therapeutics (12th ed.). New York: Macmillan, pp. 481–525.

32. Levinthal, Messengers of paradise. Mathias, R. (2003, March). New approaches seek to expand naltrexone use in heroin treatment. NIDA Notes, 17 (6), p. 8. Self, D. W. (1998). Neural substrates of drug craving and relapse in drug addiction. Annals of Medicine, 30, 379–389. Teagle, S. (2007, April). Depot naltrexone appears safe and effec- tive for heroin addiction. NIDA Notes, p. 7.

33. Goode, E. (1999). Drugs in American society (5th ed.). New York: McGraw-Hill, p. 328. McHugh and Kreek, Medical consequences, pp. 326–327. Strang, J.; Griffiths, P.; and Gossop, M. (1997). Heroin smoking by “chas- ing the dragon”: Origins and history. Addiction, 92, 673–684.

34. Buxton, J. A.; Sebastian, R.; Clearsky, L.; Angus, N.; Shah, L.; et al. (2011). Chasing the dragon – characterizing cases of leukoencephalopathy associated with heroin inhalation in British Columbia. Harm Reduction Journal, 8, 3.

35. McHugh and Kreek, Medical consequences.

36. Johnson, B. D.; Goldstein, P. J.; Preble, E.; Schmeidler, J.; Lipton, D. S.; et al. (1985). Taking care of business: The economics of crime by heroin abusers. Lexington, MA: Lexington Books.

37. Zinberg, N. E. (1984). Drug, set, and setting: The basis for controlled intoxicant use. New Haven, CT: Yale University Press, pp. 46–81.

38. Hser, Y. I.; Hoffman, V.; Grella, C.; and Douglas A. M. (2001). A 33-year follow-up of narcotics addicts. Archives of General Psychiatry, 58, 503–508. Goode, E. Drugs in American Society (8th ed.). New York: McGraw-Hill, pp. 278–281. National Institute on Drug Abuse (2001). 33-year study finds lifelong, lethal consequences of heroin addiction. NIDA Notes, 16 (4), 1, 5, 7. Quotation on p. 5. Treaster, J. B. (1992, July 22). Executive’s secret struggle with heroin’s powerful grip. New York Times, pp. A1, B4.

39. Schuckit, M. A. (2006). Drug and alcohol abuse: A clini- cal guide to diagnosis and treatment (6th ed.). New York: Springer, pp. 178-182.

40. Stitzer, M. L.; Bickel, W. K.; Bigelow, G. E.; and Liebson, I.A. (1986). Effect of methadone dose contin- gencies on urinalysis test results of polydrug-abusing methadone-maintenance patients. Drug and Alcohol Dependence, 18, 341–348.

41. Maddux, J. F., and Desmond, D. P. (1997). Outcomes of methadone maintenance 1 year after admission. Jour- nal of Drug Issues, 27, 225–238. Sees, K. L.; Delucchi, K. L.; Masson, C.; Rosen, A.; Clark, H. W.; et al. (2000). Methadone maintenance vs. 180-day psychosocially enriched detoxification for treatment of opioid depen- dence. Journal of the American Medical Association, 283, 1303–1310.

42. Office of National Drug Control Policy (2000, April). Methadone. ONDCP Drug Policy Information Clearing- house Fact Sheet. Washington, DC: Office of National Drug Control Policy.

43. Wasserman, D. A.; Korcha, R.; Havassy, B. E.; and Hall, S. M. (1999). Detection of illicit opioid and cocaine use in methadone maintenance treatment. American Journal of Drug and Alcohol Abuse, 25, 561–571.

44. Faupel, C. E. (1991). Shooting dope: Career patterns of hard-core heroin users. Gainesville: University of Florida Press, pp. 170–173. Gollnisch, Gernot (1997). Multiple predictors of illicit drug use in methadone maintenance clients. Addictive Behaviors, 22, 353–366. Substance Abuse and Mental Health Services Administration (2003, January). Narcotic analgesics. The DAWN report. Rock- ville, MD: Substance Abuse and Mental Health Services Administration, Figure 2.

45. Eissenberg, T.; Bigelow, G. F.; Strain, E. C.; Walsh, S. L.; Brooner, R. K.; et al. (1997). Dose-related efficacy of levomethadryl acetate for treatment of opioid depen- dence: A randomized clinical trial. Journal of the Ameri- can Medical Association, 277, 1945–1951.

46. Martin, K. R. (2004, September). Once-a-month medi- cation for heroin addiction? NIDA Notes, 19 (3), p. 9.

142 ■ Part Two Legally Restricted Drugs in Our Society

Mitka, M. (2003). Office-based primary care physi- cians called on to treat the “new” addict. Journal of the American Medical Association, 290, 735–736. Butrans (buprenorphine) Transdermal System CIII now avail- able. News and media release, Purdue Pharma, Janu- ary 20, 2011.

47. Martin, S. S.; O’Connell, D. J.; Paternoster, R.; and Bachman, R. D. (2011). The long and winding road to desistance from crime for drug-involved offenders: The long-term influence of TC treatment on re-arrest. Journal of Drug Issues, 11, 179-196. National Institute on Drug Abuse (2002). Therapeutic community. National Institute on Drug Abuse Research Report. Rockville, MD: National Institute on Drug Abuse.

48. Allan, L.; Hays, H.; Jensen, N.H.; Le Polain de Waroux, B.; Bolt, M.; et al. (2001). Randomised crossover trial of transdermal fentanyl and sustained-release oral morphine for treating chronic non-cancer pain. British Medical Journal, 322, 1154–1158.

49. Julien, R. M. (2005). A primer of drug action (10th ed.). New York: Worth, pp. 461-500.

50. Meier, B. (2012, April 9). Tightening the lid on pain prescriptions. New York Times, pp. A1, A12. Rosenberg, D. (2001, April 9). How one town got hooked. Newsweek, pp. 49–50. Tavernise, S. (2011, April 20). Ohio county losing its young to painkillers’ grip. New York Times, pp. A1, A16. Van Sant, W.; Peddie, S.; and Lewis, R. (2011, December 26). Millions for doctor-shoppers. Newsday, pp. A4-A5. Substance Abuse and Mental Health Services

Administration (2010, November/December). Rise in treatment admissions for prescription pain relievers. SAMHSA News, p. 19.

51. Basbaum, A. I., and Julius, D. (2006, June). Toward better pain control. Scientific American, pp. 60–67. Meier, B. (2003, November 23). The delicate balance between pain and addiction. New York Times, pp. F1, F6. FDA approves new formulation of OxyContin (2010, April 5). News release from the U.S. Food and Drug Administration, Washington, DC.

52. Goodnough, A., and Zezima, K. (2011, June 16). Drug is harder to abuse, but users persevere. New York Times, p. A21. RPT-painkiller Opana, new scourge of rural America (2012, March 12). Reuters News Service.

53. Associated Press (2011, January 23). FDA orders lower doses in prescription painkillers.

54. Centers for Disease Control and Prevention (2012, July). Vital Signs: Prescription painkiller overdoses. Atlanta, GA: Centers for Disease Control and Pre- vention. Centers for Disease Control and Preven- tion (2011, November 4). Vital signs: Overdoses of prescription opioid pain relievers—United States, 1999-2008. Morbidity and Mortality Weekly Report , 60, 1487-1492. Johnston, O’Malley, Bachman, and Schulenberg, Monitoring the Future, Table 2-2. Sub- stance Abuse and Mental Health Services Administra- tion, Results from the 2011 National Survey of Drug Use and Health: Detailed tables, Tables 1.85A and 1.85B. 1.89A, and 1.89B.

143

I was forced to interrupt my work in the laboratory in

the middle of the afternoon and proceed home, being

affected by a remarkable restlessness combined with a

slight dizziness. At home I lay down and sank into a not

unpleasant intoxicated-like condition, characterized by

an extremely stimulated imagination. In a dreamlike state

with eyes closed . . . I perceived an uninterrupted stream of

fantastic pictures, extraordinary shapes with intense, kalei-

doscopic play of colors.

—Albert Hofmann, the discoverer of LSD, reflecting on the day he took a sample of the drug

LSD: My Problem Child (1980)

After you have completed this chapter, you should have an understanding of

▶ The classification of hallucinogenic drugs

▶ The history of LSD

▶ Facts and fiction about LSD effects

▶ Prominent hallucinogens other than LSD

▶ The special dangers of MDMA (Ecstasy), phencyclidine (PCP), and ketamine

▶ Current issues concerning Salvia divinorum (Salvia) abuse

C h a p t e r

6LSD and Other Hallucinogens

144 ■ Part Two Legally Restricted Drugs in Our Society

On an April afternoon in 1943, Albert Hofmann, a research chemist at Sandoz Pharmaceuticals in Basel, Switzerland, went home early from work, unaware that his fingertips had made contact with an extremely min- ute trace of a new synthetic chemical he had been testing that day. The chemical was lysergic acid diethylamide (LSD), and, as the opening passage indicates, Hofmann unknowingly experienced history’s first “acid trip.”

Three days later, having pieced together the ori- gin of his strange experience, he decided to try a more deliberate experiment. He chose a dose of 0.25 mg, a concentration that could not, so he thought, possibly be effective. His plan was to start with this dose and gradu- ally increase it to see what would happen.

The dose Hofmann had considered inadequate was actually about five times greater than an average dose for LSD. As he later recalled his experience,

My condition began to assume threatening forms. Everything in my field of vision wavered and was distorted as if seen in a curved mirror. I also had the sensation of being unable to move from the spot.1

A little while later, his experience worsened:

The dizziness and sensation of fainting became so strong at times that I could no longer hold myself erect, and had to lie down on a sofa. My surround- ings had now transformed themselves in more terrify- ing ways. Everything in the room spun around, and the familiar objects and pieces of furniture assumed grotesque, threatening forms. . . . I was seized by the dreadful fear of going insane. I was taken to another place, another time.2

His experience then became pleasant:

Kaleidoscopic, fantastic images surged in on me, alternating, variegated, opening and then closing themselves in circles and spirals. . . . It was particu- larly remarkable how every acoustic perception, such as the sound of a door handle or a passing automo- bile, became transformed into optical perceptions. Every sound generated a vividly changing image, with its own consistent form and color.3

Hofmann’s vivid remembrances are presented here at length because they succinctly convey some of

the major facets of a hallucinogenic drug experience: the distortions of visual images and body sense, the frightening reaction that often occurs when everyday reality is so dramatically changed, and the strange inter- mingling of visual and auditory sensations. These effects will be considered later in more detail as this chapter explores the bizarre world of hallucinogenic drugs.

Like many of the drugs that have been examined in the preceding chapters, hallucinogenic drugs such as LSD and several others have a story that belongs both in our contemporary culture and in the distant past. Hofmann worked in the modern facilities of an interna- tional pharmaceutical company, but the basic material on his laboratory bench was a fungus that has been around for millions of years. It has been estimated that as many as 6,000 plant species around the world have some psychoac- tive properties.4 This chapter will focus on a collection of special chemicals called hallucinogenic drugs or simply hallucinogens, often pharmacologically dissimilar to one another but with the common ability to distort perceptions and alter the user’s sense of reality.

A Matter of Definition

Definitions are frequently reflections of one’s attitude toward the thing one is defining, and the terminology used to describe hallucinogens is no exception. For those who view these drugs with a “positive spin,” par- ticularly for those who took LSD in the 1960s, hallu- cinogens have been described as psychedelic, meaning “mind-expanding” or “making the mind manifest.” In cases where a spiritual experience has been reported, such as with the ingestion of ayahuasca, hallucinogens have been called entheogenic, meaning “generating the divine within.” On the other hand, for people who view these drugs with more alarm than acceptance, the popu- lar descriptive adjectives have been psychotomimetic,

lysergic acid diethylamide (LSD) (lye-SER-jik ASS-id di-ETH-il-la-mide): A synthetic, serotonin-related hallucinogenic drug.

hallucinogens (ha-LOO-sin-oh-jens): A class of drugs producing distortions in perception and body image at moderate doses.

by the numbers . . .

566,990 Approximate number of LSD doses in one ounce of pure LSD, based on 50 micro- grams as a typical LSD dosage level

1 The number of documented cases of deaths due to LSD ingestion alone, since 1960

Source: Fysh, R. R.; Oon, M. C. H.; Robinson, K. N.; Smith, R. N.; White, P. C.; and Whitehouse, M. J. (1985). A fatal poisoning with LSD. Forensic Science International, 28, 109–113.

Chapter 6 LSD and Other Hallucinogens ■ 145

meaning “having the appearance of a psychosis,” psy- chodysleptic, meaning “mind-disrupting,” or even worse, psycholytic, meaning “mind-dissolving.”

As a result of all this emotional baggage, describing these drugs as hallucinogenic, meaning “hallucination- producing,” is probably the most even-handed way of defining their effects; that is the way they will be referred to in this chapter. Some problems, however, still need to be considered. Technically, a hallucination is the reported perception of something that does not physi- cally exist. For example, a schizophrenic patient might hear voices that no one else hears, and therefore we must conclude (at least the nonschizophrenic world must con- clude) that such voices are not real. In the case of hallu- cinogens, the effect is more complicated because we are dealing with a perceived alteration in the existing physi- cal environment. Some researchers have suggested using the term illusionogenic as a more accurate way of describ- ing drugs that produce these kinds of experiences.

We also should be aware of another qualification when we use the term “hallucinogen.” Many drugs that produce distinctive effects when taken at low to moderate dose levels turn out to produce hallucinations when either

the dose levels are extremely high or drug use is extended over a period of time. Examples of this possibility appeared in Chapter 4 with cocaine and amphetamines and will appear in Chapter 13 with inhalants. Here the category of hallucinogens will be limited to those drugs that produce marked changes in perceived reality at relatively low dos- ages and over a relatively short time interval.

Classifying Hallucinogens

It is relatively easy to define what hallucinogens are by virtue of their effects on the users, but classifying them can be complicated. In general, most hallucinogens can be classified in terms of the particular neurotransmitter in the brain (see Chapter 3) that bears a close resem- blance to the molecular features of the drug. Basically, we are speaking of three possible neurotransmitters: serotonin, norepinephrine, and acetylcholine. A rela- tively small number of hallucinogens, however, bear no resemblance to any neurotransmitter at all.

Table 6.1 shows the overall four-group classification scheme. The first three categories are (1) hallucinogens

TAbLE 6.1

Major categories of hallucinogens

CATEgORy SOuRCE

Hallucinogens related to serotonin

lysergic acid diethylamide (LSD) a synthetic derivative of lysergic acid, which is, in turn, a component of ergot psilocybin various species of North American mushrooms lysergic acid amide or morning glory seeds morning glory seeds dimethyltryptamine (DMT) the bark resin of several varieties of trees and some nuts native to Central and

South America harmine the bark of a South American vine

Hallucinogens related to norepinephrine

mescaline the peyote cactus in Mexico and the U.S. Southwest 2,5,-dimethoxy-4-methylamphetamine (DOM or, more commonly, STP)

a synthetic, mescaline-like hallucinogen

MDMA (Ecstasy) and MDA two synthetic hallucinogens

Hallucinogens related to acetylcholine

atropine Atropa belladonna plant, known as deadly nightshade, and the datura plant scopolamine (hyoscine) roots of the mandrake plant, henbane herb, and the datura plant hyoscyamine roots of the mandrake plant, henbane herb, and the datura plant ibotenic acid Amanita muscaria mushrooms

Miscellaneous hallucinogens

phencyclidine (PCP) a synthetic preparation, developed in 1963, referred to as angel dust

ketamine (K) a PCP-like hallucinogen

Salvia divinorum or Salvia a hallucinogenic Mexican herb, in the mint family

Source: Schultes, R. E., and Hofmann, A. (1979). Plants of the gods: Origins of hallucinogenic use. New York: McGraw-Hill.

146 ■ Part Two Legally Restricted Drugs in Our Society

that are chemically similar to serotonin (LSD, psilocy- bin, morning glory seeds, DMT, and harmine), (2) hal- lucinogens that are chemically similar to norepinephrine (mescaline, DOM, MDMA, and MDA), and (3) hal- lucinogens that are chemically similar to acetylcholine (atropine, scopolamine, hyoscyamine, and ibotenic acid). The fourth category comprises three hallucinogens (PCP, ketamine, and Salvia divinorum) that are chemically unlike any known neurotransmitter; these drugs will be called miscellaneous hallucinogens. Most of these drugs have natural botanical origins (see four examples in Figure 6.1).

Lysergic Acid Diethylamide (LSD)

The most widely known hallucinogen is LSD, which does not exist in nature but is synthetically derived from ergot, a fungus present in moldy rye and other grains. One of the compounds in ergot, lysergic acid, is highly toxic, inducing a condition called ergotism.

Historians have surmised that widespread epidemics of ergotism (called St. Anthony’s fire) occurred periodi- cally in Europe during the Middle Ages, when extreme famine forced people to bake bread from infected grain (see Drugs . . . in Focus on page 147).

In one particularly deadly episode in 944, an out- break of ergotism claimed as many as 40,000 lives. The features of this calamity were twofold. One form of ergotism produced a reduction in blood flow toward the extremities, leading to gangrene, burning pain, and the eventual loss of limbs. The other form produced a tingling sensation on the skin, convulsions, disordered thinking, and hallucinations.5

Even though the link between this strange affliction and ergot in moldy grain has been known since the 1700s, outbreaks of ergotism have continued to occur in recent times. A major outbreak occurred in Pont-Saint-Esprit, a small French village, in 1951. Hundreds of townspeople went totally mad on a single night:

Many of the most highly regarded citizens leaped from windows or jumped into the Rhône, screaming that their heads were made of copper, their bodies wrapped in snakes, their limbs swollen to gigantic size or shrunken to tiny appendages. . . . Animals went berserk. Dogs ripped bark from trees until their teeth fell out.6

ergot (ER-got): A fungus infecting rye and other grains.

ergotism: A physical and/or psychological disorder acquired by ingesting ergot-infected grains. One form of ergotism involves gangrene and eventual loss of limbs; the other form is associated with convulsions, disordered thinking, and hallucinations.

(d)(a) (c)(b)

F i g u R E 6 . 1

Botanical sources for four hallucinogenic drugs: (a) Claviceps tulasne (ergot), (b) Amanita muscaria (ibotenic acid), (c) Atropa belladonna (atropine), and (d) Datura stramonium, called jimsonweed (atropine, scopolamine, and hyoscyamine). These sources are not shown to the same scale; actually, they differ in size.

Chapter 6 LSD and Other Hallucinogens ■ 147

Albert Hofmann’s professional interest in lyser- gic acid centered on its ability to reduce bleeding and increase contractions in smooth muscle, particularly the uterus. He was trying to find a nontoxic chemical ver- sion that would be useful in treating problems associated with childbirth. The LSD molecule was the twenty-fifth in a series of variations that Hofmann studied in 1938, and his creation was officially named LSD-25 for that reason. He thought at the time that the compound had possibilities for medical use but then went on to other pursuits. He returned to these investigations five years later, in 1943, the year of his famous LSD experience.

The Beginning of the Psychedelic Era Sandoz Pharmaceuticals applied for Food and Drug Administration (FDA) approval of LSD in 1953. As was common practice at the time, the company sent out samples of LSD to laboratories around the world for sci- entific study. The idea was that LSD might be helpful

in the treatment of schizophrenia by allowing psychia- trists to gain insight into subconscious processes, which this drug supposedly unlocked. One of the researchers intrigued by the potential psychotherapeutic applica- tions of LSD was the psychiatrist Humphrey Osmond of the University of Saskatchewan in Canada, who coined the word “psychedelic” to describe its effects and whose interest also extended to other hallucinogens, such as mescaline.

In 1953, Osmond introduced the British writer Aldous Huxley to mescaline, and Huxley later reported his experiences, under Osmond’s supervision, in his essay The Doors of Experience. Prior to 1960, LSD was being administered to humans under fairly limited cir- cumstances, chiefly as part of research studies in psychi- atric hospitals and psychotherapy sessions on the West Coast. As would be revealed later in court testimony in the 1970s, there were also top-secret experiments conducted by the Central Intelligence Agency (CIA), which was interested in LSD for possible application in

Drugs . . . in Focus

Strange Days in Salem: Witchcraft or Hallucinogens? In the early months of 1692, in Salem, Massachusetts, eight young girls suddenly developed a combination of bizarre symptoms: disordered speech, odd body postures, and convulsive fits. They also began to accuse various townspeople of witchcraft. During the summer, in a series of trials, more than 150 people were convicted of being witches and 20 were executed. Accusations were also made in neighboring villages in the county and in Connecticut. Nothing approaching the magnitude of the Salem witch trials has since occurred in American history.

Over the years, a number of theories have attempted to account for these strange events: a case of adolescent pranks, general hysteria, or some kind of political scape- goating. An interesting and controversial speculation has been advanced that these girls were showing the halluci- nogenic and convulsive symptoms of ergotism, acquired from fungus-infected rye grain. Arguments that support this theory include the following:

• Rye grain, once harvested, was stored in barns for months, and the unusually moist weather in the area that year could have promoted the growth of ergot

fungus during storage. Of twenty-two Salem households with some afflicted member, sixteen were located close to riverbanks or swamps.

• Children and teenagers would have been particularly vulnerable to ergotism because they ingest more food, and hence more poison, per pound of body weight than do adults.

• The Salem girls as well as the accused “witches” frequently displayed hallucinatory behavior and physical symptoms common to convulsive ergotism.

The role of ergotism in the Salem witch trials of 1692 has been vigorously debated by both historians and phar- macologists. The readings listed below provide more infor- mation on this intriguing possibility.

Sources: in favor: Caporael, L. R. (1976). Ergotism: The Satan loosed in Salem? Science, 192, 21–26. Matossian, M. K. (1982). Ergot and the Salem witchcraft affair. American Scientist, 70, 355–357. Matossian, M.K. (1989). Poisons of the past: Molds, epidemics, and history. New Haven, CT: Yale University Press, pp. 113–122. Against: Spanos, N. P., and Gottlieb, J. (1976). Ergotism and the Salem village witch trials. Science, 194, 1390–1394.

148 ■ Part Two Legally Restricted Drugs in Our Society

espionage work. Word of its extraordinary effects, how- ever, gradually spread to regions outside laboratories or hospitals. One of those who picked up on these events was a young clinical psychologist and lecturer at Harvard University named Timothy Leary.

Leary’s first hallucinatory experience (in fact, his first psychoactive drug experience of any kind, other than alcoholic intoxication) was in Mexico in 1960, when he ate some mushrooms containing the hallucino- gen psilocybin. This is his recollection of his response:

During the next five hours, I was whirled through an experience which could be described in many ex- travagant metaphors but which was above all and without question the deepest religious experience of my life.7

Back at Harvard, his revelations sparked the inter- est of a colleague, Richard Alpert (later to be known as Baba Ram Dass). The two men were soon holding psilocybin sessions with university students and who- ever else was interested, on and off campus. At first these studies retained some semblance of scientific control. For example, a physician was on hand, and objective observers of behavior reported the reactions of the subjects. Later, these procedures were altered. Physicians were no longer invited to the sessions, and Leary himself began taking the drug at the same time. His argument was that he could communicate bet- ter with the subject during the drug experience, but his participation seriously undermined the scientific nature of the studies.

In 1961 Leary, Alpert, and other associates turned to LSD as the focus of their investigations, in their homes and other locations off the Harvard campus. Although these experiments were technically separate from the university itself, public relations concerns on the part of the Harvard administration were mounting. Leary further aggravated the situation through his increasingly incendiary writings. In a 1962 article published in the Bulletin of the Atomic Scientists, he suggested that the Soviets could conceivably dump LSD into the water supply and that, to prepare for such an attack, Ameri- cans should dump LSD into their own water supply so that citizens would know what to expect. Needless to say, the U.S. government was not amused.

In 1963, after a Harvard investigation, Leary and Alpert were dismissed from their academic positions, making it the first time in the twentieth century that a Harvard faculty

member had been fired. As you can imagine, such events brought enormous media exposure. Leary was now “Mr. LSD” (see Portrait), and suddenly the public became acquainted with a class of drugs that had been previously unknown to them.8

For the rest of the 1960s, LSD became not only a drug but also one of the symbols for the cultural revolt of a generation of youth against the perceived inadequa- cies of the established, older generation. Leary himself told his followers that they were “the wisest and holiest generation” and advised them to “turn on, tune in, and drop out.”9 The era has been described in this way:

There were psychedelic churches, ashrams, rock festivals, light shows, posters, comic books and newspapers, psychedelic jargon and slang. Every middle-sized city had its enclaves, and there was a drug culture touring circuit. . . . Everyone had his own idea of what was meant by turning on, tuning in, and dropping out—his own set and setting—and the drug culture provided almost as many variations in doctrine, attitude, and way of life, from rational and sedate to lewd and violent, as the rest of society.10

In congressional hearings on LSD use by the nation’s youth, scientists, health officials, and law- enforcement experts testified to a growing panic over the drug. Newspaper stories emphasized the dangers with alarmist headlines: “A monster in our midst—a drug called LSD” and “Thrill drug warps mind, kills,” among them. Sandoz quietly allowed its LSD patent to lapse in 1966 and did everything it could to distance itself from the controversy. Hofmann himself called LSD his “problem child.”

Multicolored images such as these, inspired by the LSD experience, epitomized the psychedelic era of the 1960s.

Chapter 6 LSD and Other Hallucinogens ■ 149

In 1966, LSD was made illegal, later becoming a Schedule I drug, with possession originally set as a mis- demeanor and later upgraded to a felony. By the 1970s, LSD had become entrenched as a street drug, and taking LSD had become a component of the already dangerous world of illicit drugs. The story of LSD will be updated in a later section, but first it is important to understand the range of effects that LSD typically produces.

Acute Effects of LSD LSD is considered one of the most powerful psychoac- tive drugs known. Its potency is so great that effective dose levels have to be expressed in terms of micrograms (millionths of a gram), often called mikes. The typical street dose ranges from 50 to 150 micrograms, though sellers often claim that their product contains more. The effective dose can be as small as 10 micrograms, with only one-hundredth of a percent being absorbed into

the brain. You can appreciate the enormous potency of LSD by comparing these figures to the fact that a single regular-strength aspirin tablet contains 325,000 micro- grams of aspirin.11

Taken orally, LSD is rapidly absorbed into the bloodstream and the brain, and its effects begin to be felt within thirty to sixty minutes, reaching a peak in about two to four hours. Within four to twelve hours, LSD effects are over.12

Surprisingly, given its extreme potency, the toxic- ity of LSD is relatively low. Generalizing from studies of animals given varying doses of LSD, we can estimate that a lethal dose of LSD for humans would have to be roughly 300 to 600 times the effective dose, a fairly comfortable margin of safety. In 2011, the DAWN statis- tics showed that less than 0.1 percent of all drug-related emergency department visits were associated with the ingestion of LSD. To this day, there has been only one definitive case in which a death has been attributed solely to an LSD overdose.13

P O R T R A i T Timothy Leary—Nutty Professor or Psychedelic Visionary?

For the average college stu- dent, the question regarding Timothy Leary might be not “What- ever happened to that guy?” but rather “Who was this guy, anyway?” For those of you who ask the latter ques- tion, here is a capsule rendition of the life and times of Timothy Leary. Historians are only starting to come to grips with the complexity of his legacy.

Until 1960, Leary’s career was a world apart from what would follow. It had none of the unconventional- ity that would later characterize his life. As a clinical psychologist, he had written a widely acclaimed textbook and devised a respected personality test (called the Leary). An experience with psilocybin in Mexico in 1960, however, turned his life around. The more extensive his exposure to hallu- cinogenic drugs became, the more he took on the self-appointed role of Pied Piper for what was referred to then as the “acid generation.”

By the middle of the 1970s, Leary had been sentenced to twenty years

for marijuana possession (the longest sentence ever imposed

for such an offense), had gone to fed- eral prison, had escaped, had evaded the authorities in Algeria, Afghanistan, and Switzerland for a few years, had been recaptured, and finally had been released after a successful appeal of his original conviction. LSD advocacy was no longer on his agenda by this time, and in fact LSD had lost its mystique years earlier. Leary hit the college lecture circuit, talking about space mi- gration and life extension and calling himself a “stand-up philosopher.”

In the late 1980s, Leary discovered computers. He formed a software company, marketed a number of suc- cessful video games, and viewed in- teractive computer programming and virtual reality in particular as the con- sciousness expansion of the 1990s, the newest route to “cerebral stimulation.”

Leary never stopped being a social activist, with his own unique brand of opportunism. In 1994, he was detained by the police in an Austin, Texas,

airport for smoking—a cigarette, this time. Leary said that he wanted to draw attention to people being “demonized” by no-smoking restrictions.

A year after his death in 1996, Leary’s friends arranged to have his cremated remains delivered by rocket into space. It was estimated that he would orbit Earth every ninety min- utes for approximately two years or so, until his “space-hearse” would eventu- ally burn up during reentry. As his fol- lowers put it at the time, it was fitting that this would be his “ultimate trip.”

Sources: Brozan, N. (1994, May 12). Chronicle: Timothy Leary lights up. New York Times, p. D26. Greenfield, R. (2006). Timothy Leary: A biography. New York: Harcourt. L.; Martin A.; and Shlain, B. (1985). Acid dreams: The com- plete social history of LSD. New York: Grove Weidenfeld. Simons, M. (1997, April 22). A final turn-on lifts Timothy Leary off. New York Times, pp. A1, A4. Stone, J. (1991, June). Turn on, tune in, boot up. Discover, pp. 32–35.

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Street forms of LSD may contain color additives or adulterants with specific flavors, but the drug itself is odorless, tasteless, and colorless. LSD is sold on the street in single-dose “hits.” It is typically swallowed in the form of powder pellets (microdots) or gelatin chips (win- dowpanes) or else licked off small squares of absorbent paper that have been soaked in liquid LSD (blotters). In the past, blotters soaked with LSD have been deco- rated with pictures of mystical symbols and signs, rocket ships, or representations of Mickey Mouse, Snoopy, Bart Simpson, or other popular cartoon characters.

LSD initially produces an excitation of the sym- pathetic autonomic activity: increased heart rate, elevated blood pressure, dilated pupils, and a slightly raised body temperature. There is an accompanying feeling of restlessness, euphoria, and a sensation that inner tension has been released. There may be laugh- ing or crying, depending on one’s expectations and the setting.14

Between thirty minutes and two hours later, a “psy- chedelic trip” begins, characterized by four distinctive features. The best way to describe these effects is in the words of individuals who have experienced them:15

■ Images seen with the eyes closed.

Closing my eyes, I saw millions of color droplets, like rain, like a shower of stars, all different colors.

■ An intermingling of senses called synesthesia, which usually involves sounds being perceived as hallucina- tory visions.

I clapped my hands and saw sound waves passing before my eyes.

■ Perception of a multilevel reality.

I was sitting on a chair and I could see the molecules. I could see right through things to the molecules.

■ Strange and exaggerated configurations of common objects or experiences.

A towel falling off the edge of my tub looked like a giant lizard crawling down.

When my girlfriend was peeling an orange for me, it was like she was ripping a small animal apart.

During the third and final phase, approximately three to five hours after first taking LSD, the following features begin to appear:

■ Great swings in emotions or feelings of panic.

It started off beautifully. I looked into a garden . . . and suddenly, it got terrible . . . and I started to cry. . . . And then, my attention wandered, and something else was happening, beautiful music was turned on. . . . Then suddenly I felt happy.

■ A feeling of timelessness.

Has an hour gone by since I last looked at the clock? Maybe it was a lifetime. Maybe it was no time at all.

■ A feeling of ego disintegration, or a separation of one’s mind from one’s body.

Boundaries between self and nonself evaporate, giv- ing rise to a serene sense of being at one with the universe. I recall muttering to myself again and again, “All is one, all is one.”

Whether these strong reactions result in a “good trip” or a “bad trip” depends heavily on the set of expec- tations for the drug, the setting or environment in which the LSD is experienced, and the overall psychological health of the individual.

Effects of LSD on the Brain LSD closely resembles the molecular structure of sero- tonin. Therefore, it is not surprising that LSD should have effects on receptors in the brain that are sensitive to serotonin (see Chapter 3). As a result of research in

synesthesia: A subjective sensation in a modality other than the one being stimulated. An example is a visual experience when a sound is heard.

A microdot tablet of LSD positioned against a British post- age stamp (to the left of the queen) underscores the minute amount necessary for a single dose.

Chapter 6 LSD and Other Hallucinogens ■ 151

the 1980s, it turns out that the critical factor behind LSD’s hallucinogenic effects lies in its ability to stimu- late a special subtype of serotonin-sensitive receptors called serotonin-2A receptors. In fact, all hallucinogens, even those drugs whose structures do not resemble sero- tonin, have the ability to excite these receptors. Drugs that specifically block serotonin-2A receptors, leaving all other subtypes unchanged, will block the behav- ioral effects of hallucinogens. In addition, the ability of a particular drug to produce hallucinogenic effects is directly proportional to its ability to bind to serotonin-2A receptors.16

Patterns of LSD Use The enormous publicity surrounding Timothy Leary and his followers in the 1960s made LSD a house- hold word. As many as fifty popular articles about LSD were published in major U.S. newspapers and maga- zines between March 1966 and February 1967 alone. By 1970, however, the media had lost interest, and hardly anything was appearing about LSD. Even so, while media attention was diminishing, the incidence of LSD abuse was steadily rising. In four Gallup Poll surveys conducted between 1967 and 1971, the per- centage of college students reported to have taken LSD at least once in their lives rose dramatically, from 1 to 18 percent.17

From the middle 1970s to the early 1990s, the num- bers showed a steady decline. By 1986, the University of Michigan survey indicated that the lifetime inci- dence of LSD taking among high school seniors was 7 percent, down from 11 percent in 1975. By the end of the 1990s, however, prevalence rates were once again on the rise, reaching and later exceeding the levels of a quarter- century earlier. Since 1997 when the prevalence rate was about 14 percent, LSD use has declined sub- stantially. Four percent of high school seniors in 2011 reported taking LSD at some time in their lives. A paral- lel trend has been observed in college students.18

It should be noted that today’s LSD users are dif- ferent from those of a previous generation in a number of ways. Typical LSD users now take the drug less fre- quently. And because the dosage of street LSD is pres- ently about one-fourth the level common to the 1960s and 1970s, they remain high for a briefer period of time. Their motivation behind using LSD is also not the same. They report using LSD as a club drug, simply to get high, rather than to explore alternate states of con- sciousness or gain a greater insight into life. For current users, LSD no longer has the symbolic significance that it had in an earlier time.19

Facts and Fiction about LSD

Given the history of LSD use and the publicity about it, it is all the more important to look carefully at the facts about LSD and to unmask the myths. It is useful to examine six basic questions that are frequently asked about the acute and chronic effects of this drug.

Will LSD Produce Substance Dependence? There are three major reasons why LSD is not likely to result in drug dependence, despite the fact that the experience at times is quite pleasant. First, LSD and other hallucinogens cause the body to build up a toler- ance to their effects faster than any other drug category. As a result, one cannot remain on an LSD-induced high day after day, for an extended period of time. Second, LSD is not the drug for someone seeking an easy way to get high. As one drug expert has put it,

The LSD experience requires a monumental effort. To go through eight hours of an LSD high—sensory bombardment, psychic turmoil, emotional insecurity, alternations of despair and bliss, one exploding insight upon the heels of another, images hurtling through the mind as fast as the spinning fruit of a slot machine—is draining and exhausting in the extreme.20

Third, the LSD experience seems to control the user rather than the other way around. It is virtually impossible to “come down” from LSD at will. Besides, the unpredictability of the LSD experience is an unpop- ular feature for those who would want a specific and reliable drug effect every time the drug is taken.

Will LSD Produce a Panic Attack or Psychotic Behavior? One of the most notorious features of LSD is the pos- sibility of a bad trip. Personal accounts abound of sweet, dreamlike states rapidly turning into nightmares. Per- haps the greatest risks are taken when a person is slipped a dose of LSD and begins to experience its effect with- out knowing that he or she has taken a drug. But panic reactions may also occur when a person is fully aware of having taken LSD. Although the probability of having a bad trip is difficult to estimate, there are very few regu- lar LSD abusers who have not experienced a bad trip or had a disturbing experience as part of an LSD trip. The best treatment for adverse effects is the companionship and reassurance of others throughout the period when

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LSD is active. Health Alert includes some specific pro- cedures for dealing with LSD panic episodes.

Despite the possibility of an LSD panic, there is no strong evidence that the panic will lead to a permanent psychiatric breakdown. Long-term psychiatric problems are relatively uncommon; one study conducted in 1960 showed that there was no greater probability of a person attempting suicide or developing a psychosis after taking LSD than when undergoing ordinary forms of psycho- therapy.21 The incidents that do occur typically involve people who were unaware that they were taking LSD, showed unstable personality characteristics prior to tak- ing LSD, or were experiencing LSD under hostile or threatening circumstances.

The possible link between the character of LSD effects and certain symptoms of schizophrenia also has been examined closely. It is true that on a superficial level, the two behaviors show some similarities, but there are important differences. LSD hallucinations are primarily visual, are best seen in the dark, and, as we noted earlier, are more accurately characterized as illu- sions or pseudohallucinations; schizophrenic hallucina- tions are primarily auditory, are seen with open eyes, and qualify as true hallucinations. Individuals taking LSD are highly susceptible to suggestion and usually try to communicate the experience to others, whereas the schizophrenic individual is typically resistant to sug- gestion and withdrawn from his or her surroundings.

Therefore, it is unlikely that LSD is mimicking the experience of schizophrenia (see Chapter 15).

Will LSD Increase Your Creativity? The unusual visual effects of an LSD experience may lead you to assume that your creativity is enhanced, but the evidence indicates otherwise. Professional artists and musicians creating new works of art or songs while under the influence of LSD typically think that their creations are better than anything they have yet produced, but when the LSD has worn off, they are far less impressed. Con- trolled studies generally show that individuals under LSD feel that they are creative, but objective ratings do not show a significant difference from levels prior to the LSD.22

Will LSD Damage Your Chromosomes? In March 1967, a study published in the prestigious scien- tific journal Science described a marked increase in chro- mosomal abnormalities in human white blood cells that had been treated with LSD in vitro (that is, the cells were outside the body at the time).23 Shortly after, three other studies were reported in which chromosomal abnormali- ties in the white blood cells of LSD abusers were higher than those of people who did not use drugs, whereas three additional studies reported no chromosomal effect at all.

H E A L T H A L E R T !

Emergency guidelines for a bad Trip on LSD • Stay calm with the individual. Do not move around

quickly, shout, cry, or become hysterical. Any sense of panic on your part will make an LSD panic worse. Speak in a relaxed, controlled manner.

• Reassure the individual that the situation is temporary and that you will not leave until he or she returns to a normal state. Encourage the individual to breathe deeply and calmly. Advise him or her to view the trip as though watching a movie or TV program.

• Reduce any loud noises or bright lights, but do not let the individual be in the dark. Darkness tends to encourage hallucinations in a person under the influence of LSD.

• Allow the individual to move around without undue restrictions. He or she can sit, stand, walk, or lie down

if this helps the situation. You can divert attention from the panic by encouraging the individual to beat time to music or by dancing.

• If your assistance does not produce a reduction in the panic, seek out medical attention immediately.

Where to go for assistance: http://drugabuse.gov/infofacts/hallucinogens.html

The National Institute on Drug Abuse (NIDA) spon- sors an extensive series of web sites related to drug use and abuse.

Sources: Palfai, T., and Jankiewicz, H. (1991). Drugs and human behavior. Dubuque, IA: W. C. Brown, p. 445. Robbins, P. R. (1996). Hallucinogens. Springfield, NJ: Enslow Publishers, pp. 83–85. Trulson, M. E. (1985). LSD: Visions or nightmares. New York: Chelsea House, p. 101.

Chapter 6 LSD and Other Hallucinogens ■ 153

By the end of that year, a second study was pub- lished by the people whose report had started the con- troversy in the first place. They wrote that eighteen LSD abusers had two to four times the number of chromosomal abnormalities in their white blood cells, when compared with fourteen control subjects. Interest- ingly, the subjects in this study were not exactly model citizens. Every one of them had taken either amphet- amines, barbiturates, cocaine, hallucinogens, opioids, or antipsychotic medication, and some had abused more than one of these substances.

The picture was confused, to say the least. Not only were many of these studies never replicated, but many were methodologically flawed in the first place. Most important, when studies actually looked at the chro- mosomes of reproductive cells themselves for signs of breakage from exposure to LSD, the results were either ambiguous or entirely negative. By 1971, after nearly a hundred studies had been carried out, the conclusion was that LSD did not cause chromosomal damage in human beings at normal doses, and that there was no evidence of a high rate of birth defects in the children of LSD users.24 Yet, in the highly politicized climate of the late 1960s, the media tended to emphasize the negative findings without subjecting their validity or rel- evance to any scrutiny. The public image of LSD caus- ing genetic (mutation-generating) damage still persists, despite the lack of scientific evidence. This is not to say, however, that there is no basis for exercising some degree of caution. Women should avoid LSD, as well as other psychoactive and many nonpsychoactive drugs, during pregnancy, especially in the first three months.25

Will LSD Have Residual (Flashback) Effects? One of the most disturbing aspects of taking LSD is the possibility of reexperiencing the effects of the drug long after the drug has worn off—sometimes as long as several years later. These experiences are referred to as hallucinogen persisting perception disorder, or simply “flashbacks.” The likelihood of LSD flashbacks is not precisely known. Some studies estimate its rate of inci- dence as only 5 percent, whereas others estimate it as high as 33 percent. It is reasonable to assume that the range of estimates is related to differences in the dosage levels ingested.

Flashback effects sometimes can be frightening and at other times can be quite pleasant; they can occur among LSD novices or “once-only” drug takers, as well as among experienced LSD abusers. They can appear without warning, but there is a higher probability that

they will occur when the individual is beginning to go to sleep or has just entered a dark environment.26

Because they are not common to any other psychoac- tive drug, the reason why LSD flashbacks might occur is not well understood. It is possible that LSD has a peculiar ability to produce some biochemical changes that remain dormant for a period of time and then suddenly reappear. Or perhaps some remnant of the drug has the ability to persist over extended periods of time. It is also possible that individuals who ingest LSD are highly suggestible to social reminders about the original exposure to LSD.

Whether LSD produces major long-term deficits in the behavior of the user remains largely unknown. Memory problems and visuospatial impairments have been reported in some studies but not in others. Unfor- tunately, several problems persist in research studies examining long-term effects of LSD. Often, they have included either individuals with a history of psychiat- ric disorders prior to LSD ingestion or regular users of other illicit drugs and alcohol. As a result, it has been impossible to tease apart the long-term effects of LSD alone from other factors.27

Will LSD Increase Criminal or Violent Behavior? As noted in Chapter 2, it is very difficult to establish a clear cause-and-effect relationship between a drug and criminal or violent behavior. In the highly charged era of the 1960s, stories related to this question were publi- cized, and conclusions were drawn, without any careful examination of the actual facts. Take, for example, the 1964 case of a woman undergoing LSD therapy treat- ment who murdered her lover three days after her last LSD session.28 The details of the case, overlooked by most subsequent media reports, reveal that the woman had been physically abused by the man, he had caused her to have an abortion, and the woman already had a serious mental disorder before going into treatment. The fact that the homicide took place well after the LSD had left her body indicates that the murder was not pharma- cologically based (see Chapter 2). Other cases in which violent behavior appeared to be associated with an LSD experience turned out to be associated with the use of other hallucinogenic drugs instead.

It is possible, however, for an individual to “freak out” on LSD. The effects of a euphoriant drug such as LSD can lead to a feeling of invulnerability. This feeling, in turn, can prompt dangerous and possibly life-threaten- ing behavior. Although (or indeed because) we cannot reliably estimate the likelihood of these effects or pin- point the circumstances under which they might occur,

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we should recognize that psychological reactions to LSD are inherently unpredictable, and caution is advised.

Psilocybin and Other Hallucinogens Related to Serotonin

The source of the drug psilocybin is a family of mush- rooms native to southern Mexico and Central America. Spanish chroniclers in the sixteenth century wrote of “sacred mushrooms” revered by the Aztecs as teonanacatl (roughly translated as “God’s flesh”) and as capable of pro- viding extraordinary visions when eaten. Their psychoac- tive properties had been known for a long time, judging from stone-carved representations of these mushrooms discovered in El Salvador and dating back to as early as 500 b.c. Today, shamans in remote villages in Mexico and Central America (see Chapter 1) continue the use of psi- locybin mushrooms, among other hallucinogenic plants, achieve healing on both physical and spiritual levels.29

In 1955, a group of Western observers documented the hallucinogenic effects of the Psilocybe mexicana in a native community living in a remote mountainous region of southern Mexico. Three years later, samples worked their way to Switzerland, where Albert Hof- mann, already known for his work on LSD, identified the active ingredient and named it psilocybin. As was his habit, Hofmann sampled some of the mushrooms himself and wrote later of his reactions:

Thirty minutes after my taking the mushrooms, the exterior world began to undergo a Mexican charac- ter. . . . I saw only Mexican motifs and colors. When the doctor supervising the experiment bent over me to check my blood pressure, he was transformed into an Aztec priest.30

An interesting question is whether the Aztec character of these hallucinogenic effects was simply a result of suggestion, given the social context in which the drug- taking behavior was occurring, or, alternatively, Aztec designs may have been inspired over the centuries by the effects of psilocybin.

Once ingested, psilocybin loses a portion of its molecule, making it more fat-soluble and more easily

absorbed into the brain. This new version, called psilocin, is the actual agent that works on the brain. Because LSD and psilocin are chemically similar, the biochemical effects are also similar. Cross-tolerance will occur (see Chapter 3). If you develop a tolerance to LSD, you have become tolerant to psilocybin effects, and vice versa.31

Far less potent than LSD, psilocybin is effective at dose levels measured in the more traditional units of mil- ligrams, rather than in micrograms. At doses of 4 to 5 mg, psilocybin causes a pleasant, relaxing feeling; at doses of 15 mg and more, hallucinations, time distortions, and changes in body perception appear. A psilocybin trip generally lasts from two to five hours, considerably shorter than an LSD trip.

Individuals who have experienced both kinds of hallucinogens report that, compared to LSD, psilocy- bin produces effects that are more strongly visual, less emotionally intense, and more euphoric, with fewer panic reactions and less chance of paranoia. On the other hand, experimental studies of volunteers taking high doses of psilocybin have established that the drug produces drastic enough changes in mood, sensory per- ception, and thought processes to qualify as a psychotic experience.

Like LSD, psilocybin (often called simply “shrooms”) has become increasingly available as a drug of abuse. In 2011, about 38 percent of high school seniors reported that non-LSD hallucinogens (including “shrooms”) were “fairly easy” or “very easy” to get, whereas about 25 per- cent felt the same way about LSD itself.32

Lysergic Acid Amide (LAA) In addition to their reverence for psilocybin mushrooms, the Aztecs ingested locally grown morning glory seeds, calling them ololuiqui, and used their hallucinogenic effects in religious rites and healing. Like many Native

psilocybin (SiL-oh-SigH-bin): A serotonin-related hallucinogenic drug originating from a species of mushroom.

psilocin (SiL-oh-sin): A brain chemical related to serotonin, resulting from the ingestion of psilocybin.

Psilocybe mexicana mushrooms, the source of psilocybin.

Chapter 6 LSD and Other Hallucinogens ■ 155

American practices, the recreational use of morning glory seeds has survived in remote areas of southern Mexico. In 1961, Albert Hofmann (once again) identi- fied the active ingredient in these seeds as lysergic acid amide (LAA) after having sampled its hallucinogenic properties. As the chemical name suggests, this drug is closely related to LSD.

The LAA experience, judging from Hofmann’s report, is similar to that of LSD, although LAA is only one-tenth to one-thirtieth as potent, and the hallucinations tend to be dominated by auditory rather than visual images. Commercial varieties of morning glory seeds are available to the public, but to minimize their abuse, suppliers have taken the precaution of coating them with an additive that causes nausea and vomiting if they are eaten.33

Dimethyltryptamine (DMT) The drug dimethyltryptamine (DMT) is obtained chiefly from the resin of the bark of trees and nuts native to the West Indies as well as to Central and South America, where it is generally inhaled as a snuff. An oral administration does not produce psychoactive effects. The similarity of this drug’s effects to those of LSD and

its very short duration gave DMT the reputation, dur- ing the psychedelic years of the 1960s, of being “the businessman’s LSD.” Presumably, someone could take a DMT trip during lunch and be back at the office in time for work in the afternoon.

An inhaled 30-mg dose of DMT produces physio- logical changes within ten seconds, with hallucinogenic effects peaking around ten to fifteen minutes later. Para- noia, anxiety, and panic also can result at this time, but most symptoms are over in about an hour.34 A chemical found in Bufo toads is similar to DMT (see Health Line).

bufotenine (byoo-FOT-eh-neen): A serotonin-related drug obtained either from a bean plant in Central and South America or from the skin of a particular type of toad.

cyanosis (SigH-ah-NOH-sis): A tendency for the skin to turn bluish purple. It can be a side effect of the drug bufotenine.

lysergic acid amide (LAA) (lye-SER-jik ASS-id A-mide): A hallucinogenic drug found in morning glory seeds, producing effects similar to those of LSD.

dimethyltryptamine (DMT) (dye-METH-il-TRiP- ta-meen): A short-acting hallucinogenic drug.

Health Line Bufotenine and the Bufo Toad

Bufotenine is a drug with a strange past. Found in a family of beans native to Central and South America, bufotenine is better known as a chemical that can be isolated from the skin and glands of the Bufo toad, from which it gets its name. As noted in Chapter 1, Bufo toads figured prominently in the magical potions of European witches. Evidence also exists that Bufo toads were incor- porated into the ceremonial rituals of ancient Aztec and Mayan cultures. Largely as a result of these historical references, it has been widely assumed that bufotenine was the primary contributor to the psychoactive effects of these concoctions and that bufotenine itself is a powerful hallucinogen.

It turns out that these conclusions are wrong. The few studies in which human volunteers were administered bufotenine indicate that the substance induces strong excitatory effects on blood pressure and heart rate but no hallucinatory experiences. Some subjects report distorted images with high dosages of the drug, but this might well occur as oxygen is cut off from parts of the body, particu- larly the optic nerve carrying visual information to the brain. It is likely that whatever hallucinogenic effects Bufo toads may produce are brought on by another chemical

also found in these toads that functions similarly to the hallucinogen DMT.

Despite the confusion about which substance is responsible for its psychoactive properties, Bufo toads continue to fascinate the public. Wildly exaggerated and frequently unsubstantiated accounts of “toad licking” and “toad smoking” periodically circulate in the media. Reportedly, a small group calling themselves Amphibians Anonymous was formed in the late 1980s; the group’s motto was “Never has it been so easy to just say no.”

The bottom line, however, is that the dangers of consuming toad tissue are substantial. Besides the extreme cardiovascular reactions, toxic effects include a skin con- dition called cyanosis (literally, “turning blue”). Actually, that description may be an understatement. Skin color has been observed to be closer to an eggplant purple.

Sources: Horgan, J. (1990, August). Bufo abuse. Scientific American, pp. 26–27. Inciardi, J. A. (2002). The war on drugs III. Boston: Allyn and Bacon, pp. 4–5. Lyttle, T.; Gold- stein, D.; and Gartz, J. (1996). Bufo toads and bufotenine: Fact and fiction surrounding an alleged psychedelic. Journal of Psychoactive Drugs, 28, 267–290.

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Harmine Among native tribes in the western Amazon region of South America, the bark of the Banisteriopsis vine yields the powerful drug harmine. A drink contain- ing harmine, called ayahuasca, is frequently used by local shamans for healing rites. It is chemically simi- lar to serotonin, like LSD and the other hallucinogens examined so far. Its psychological effects, however, are somewhat different. Unlike LSD, harmine makes the individual withdraw into a trance, and the hallucina- tory images (often visions of animals and supernatural beings) are experienced within the context of a dream- like state. Reports among shamans refer to a sense of sus- pension in space or of flying, falling into one’s body, or experiencing one’s own death.35

Hallucinogens Related to Norepinephrine

Several types of hallucinogens have a chemical com- position similar to that of norepinephrine. As you may recall from Chapter 4, amphetamines are also chemi- cally similar to norepinephrine. Consequently, some of the norepinephrine-related hallucinogens are capable of producing amphetamine-like stimulant effects. This is the case with MDMA (Ecstasy) but not with mescaline or DOM (short for 2,5-dimethoxy-4-methylamphetamine).

Mescaline The hallucinogen mescaline is derived from the peyote plant, a spineless cactus with a small, greenish crown that grows above ground and a long carrot-like root. This cactus is found over a wide area, from the south- western United States to northern regions of South America, and many communities in these regions have discovered its psychoactive properties. Given the large distances between these groups, it is remarkable that

they prepare and ingest mescaline in a highly similar manner. The crowns of the cactus are cut off, sliced into small disks called buttons, dried in the sun, and then consumed. An effective dose of mescaline from peyote is 200 mg, equivalent to about five buttons. Peak response to the drug takes place thirty minutes to two hours after consumption. Mescaline is still used today as part of religious worship among many Native Ameri- cans in the United States and Canada (see Drugs . . . in Focus on page 157).

The psychological and physiological effects of mes- caline are highly similar to those of LSD, though some have reported that mescaline hallucinations are more sensual, with fewer changes in mood and the sense of self. Nonetheless, double-blind studies comparing the reac- tions to LSD and mescaline show that subjects cannot distinguish between the two when dose levels are equiva- lent. Although the reactions may be the same, the mes- caline trip comes at a greater price, as far as physiological reactions are concerned. Peyote buttons taste extremely bitter and can cause vomiting, headaches, and, unless the stomach is empty, distressing levels of nausea.36

Today mescaline can be synthesized as well as obtained from the peyote cactus. The mescaline molecule resembles the chemical structure of norepinephrine but stimulates the same serotonin-2A receptors as LSD and other hallucinogens that resemble serotonin. As a result, mescaline and LSD share a common brain mechanism.37

DOM A group of synthetic hallucinogens have been devel- oped that share mescaline’s resemblance to amphet- amine but do not produce the strong stimulant effects of amphetamine. One example of these synthetic drugs, DOM, appeared in the 1960s and 1970s, when it was

harmine (HAR-meen): A serotonin-related hallucino- genic drug frequently used by South American sha- mans in healing rituals.

mescaline (MES-kul-leen): A norepinephrine-related hallucinogenic drug. Its source is the peyote cactus.

peyote (pay-yO-tay): A species of cactus that is the source for the hallucinogenic drug mescaline.

DOM: A synthetic norepinephrine-related hallucino- genic drug, derived from amphetamine. DOM or a combination of DOM and LSD is often referred to by the street name STP.

The peyote cactus, source of mescaline.

Chapter 6 LSD and Other Hallucinogens ■ 157

frequently combined with LSD and carried the street name of STP. To some, the nickname was a reference to the well-known engine oil additive; to others the letters stood for “serenity, tranquility, and peace” or, alternatively, “super terrific psychedelic.” It is roughly eighty times more potent than mescaline, though still far weaker than LSD. At low doses of about 3 to 5 mg, DOM produces euphoria; with higher doses of 10 mg or more, severe hallucinations result, often lasting from sixteen to twenty-five hours. Though similar to LSD in many respects, DOM has the reputation of producing a far greater incidence of panic attacks, psychotic epi- sodes, and other symptoms of a very bad trip. Cases have been reported of STP being added as an adulterant to marijuana.38

MDMA (Ecstasy) Another synthetic norepinephrine-related hallucino- gen, abbreviated MDMA, first appeared on the scene in the 1980s. Although subject to abuse as a new designer drug, it also became known to a number of psychiatrists who used the drug as part of their therapy, believing that MDMA had a special ability to enhance empathy among their patients. In fact, some therapists at the time

MDMA (Ecstasy): There is a growing consensus of opinion that hallucinogenic drug. There is a growing consensus of opinion of his psychotherapeutic ben- efits, although there are significant adverse physical and psychological side effects.

Drugs . . . in Focus

Present-Day Peyotism and the Native American Church Among Native Americans within the United States, the ritual use of peyote buttons, called peyotism, can be traced to the eighteenth century, when the Mescalero Apaches (from whom the word mescaline was derived) adopted the custom from Mexican Indians who had been using peyote for more than three thousand years. By the late 1800s, peyotism had become widely popular among tribes from Wisconsin and Minnesota to the West Coast. It was not until the early twentieth century, however, that peyote use became incorporated into an official religious organiza- tion, the Native American Church of North America, chartered in 1918.

The beliefs of the Native American Church mem- bership, estimated to include anywhere from 50,000 to 250,000 Native Americans in the United States and Can- ada, combine traditional tribal customs and practices with Christian morality. To them, life is a choice between two roads that meet at a junction. The Profane Road is paved and wide, surrounded by worldly passions and tempta- tions. The Peyote Road is a narrow and winding path, sur- rounded by natural, unspoiled beauty; it is also a path of sobriety (since alcohol poisons the goodness of the body), hard work, caring for one’s family, and brotherly love. Only the Peyote Road leads to salvation. In their weekly ceremonies, lasting from Saturday night until Sunday afternoon, church members swallow small peyote buttons

as a sacrament, similar to the ritual of taking Holy Com- munion, or drink peyote tea. It is considered sacrilegious to take peyote outside the ceremonies in the church.

The Religious Freedom Restoration Act of 1993 estab- lished an exemption from federal and state controlled sub- stance laws when peyote is used for religious purposes in traditional Native American ceremonies. In 2005, a study found that peyote use among church members does not result in impairments on tests of memory, attention, and other aspects of cognitive functioning.

Today, a handful of people are licensed by state and federal authorities to harvest peyote for religious purposes, in south Texas near Laredo. This locale is the only place in the United States where peyote grows in the wild. As one of the harvesters has put it, “This is sacred ground to a lot of Native American tribes. To some, the land here is very holy because it is the home to the sacred peyote.”

Sources: Calabrese, J. D. (1997). Spiritual healing and hu- man development in the Native American Church: Toward a cultural psychiatry of peyote. Psychoanalytic Review, 84, 237–255. Halpern, J. H.; Sherwood, A. R.; Hudson, J. I.; Yurgelum-Tod, D.; and Pope, H. G. Jr. (2005). Psychologi- cal and cognitive effects of long-term peyote use among Native Americans. Biological Psychiatry, 58, 624–631. Milloy, Ross E. (2002, May 7). A forbidding landscape that’s Eden for peyote. New York Times, p. A20. Quotation on p. A20. Morgan, G. (1983). Recollections of the peyote road. In L. Grinspoon and J. B. Bakalar (Eds.), Psychedelic reflec- tions. New York: Human Sciences Press, pp. 91–99.

158 ■ Part Two Legally Restricted Drugs in Our Society

suggested the name empathogens (meaning “generating a state of empathy”) to describe MDMA and related drugs. Eventually, after several years of hesitations and reversals, the Drug Enforcement Administration (DEA) put MDMA permanently on the Schedule I

list of controlled substances, indicating that there is no accepted medical application for the drug. Nonetheless, in recent years, a small number of research laborato- ries have received permission to produce MDMA and study its effects under closely supervised circumstances. The treatment of post-traumatic stress disorder among veterans of the wars in Iraq and Afghanistan has been identified as a potentially useful therapeutic applica- tion. There is an increased interest in MDMA in psy- chotherapy in general, a possibility that remains for now officially prohibited by virtue of its status as Schedule I controlled substance.39

Since the early 1990s, MDMA has become promi- nent among the new club drugs (see Chapter 1) espe- cially popular at dance clubs and all-night “rave” parties. Widely available under names such as Ecstasy (not to be confused with the stimulant Herbal Ecstasy), E, XTC, X, Essence, Clarity, and Adam, MDMA has the reputa- tion of having the stimulant qualities of amphetamines and the hallucinogenic qualities of mescaline.

Assorted Ecstasy tablets.

H E A L T H A L E R T !

MDMA Toxicity: The Other Side of Ecstasy • Possible Physical Effects

Hyperthermia and heatstroke Dehydration and electrolyte depletion Irregular heartbeat or increased heart rate Kidney and liver failure Jaw-clenching and other forms of muscle spasms Long-term neurochemical changes

• Possible Psychological Effects Agitation and confusion Depression and anxiety Long-term impairments in memory recall

Note: As with other illicit drugs, adulterated versions raise significant concerns. In the case of MDMA, adulterants include dextromethorphan (a common cough suppres- sant) at approximately thirteen times the dose found in over-the-counter cough medications. At this dosage, dextromethorphan itself functions as a hallucinogen and inhibits sweating, increasing the risk of hyperthermia and heatstroke. More powerful hallucinogens and hyper- thermic drugs have also been identified as adulterants in MDMA batches.

In 2003, the federal RAVE (Reducing Americans’ Vulnerability to Ecstasy) Act was signed into law, making

it unlawful to “knowingly open, lease, rent, use, or main- tain any place, whether permanently or temporarily for the purpose of manufacturing, distributing, or using any controlled substance.” Supporters of the law view it as helping to reduce illicit drug use in dance clubs; opponents view it more as a reflection of prejudice against youth culture.

Where to go for assistance: www.nida.nih.gov/infofacts/ecstasy.html

This web site is sponsored by the National Institute on Drug Abuse and includes an extensive treatment on the hazards of Ecstasy (MDMA).

Sources: Boils, K. I. (1999). Memory impairment in absti- nent MDMA (“Ecstasy”) users. Journal of the American Medical Association, 281, 494. Chonin, N. (2003, April 27). Congress acts out against club culture. San Francisco Chronicle, p. 35. Leshner, A. I. (2002). Ecstasy abuse and control: Hearing before the Senate Subcommittee on Governmental Affairs—July 30, 2001. Statement for the record. Journal of Psychoactive Drugs, 34, 133–135. Schwartz, R. H., and Miller, N. S. (1997). MDMA (Ecstasy) and the rave: A review. Pediatrics, 100, 705–708. Stryker, J. (2001, September 25). For partygoers who can’t say no, experts try to reduce the risks. New York Times, p. F5.

Chapter 6 LSD and Other Hallucinogens ■ 159

The physical health concerns with respect to Ecstasy center on its short-term and long-term toxic- ity. The principal acute effect is severe hyperthermia (and heatstroke), which can be lethal when one ingests Ecstasy while engaged in the physical exertion in an already overheated environment. The dehydration asso- ciated with hyperthermia causes an elevation in blood pressure and heart rate and places a strain on kidney functioning. These problems are compounded by the highly risky practice of “Ecstasy stacking,” in which multiple Ecstasy tablets are taken at once or Ecstasy is combined with LSD, alcohol, marijuana, or other drugs. Ecstasy use also has been linked to long-term cog- nitive impairments and emotional difficulties. Heavy and prolonged Ecstasy use can produce confusion, anxi- ety, sleep problems, reductions in impulse control, and declines in memory and attention. In general, women show greater behavioral effects from chronic Ecstasy use than do men.40 The Health Alert feature on page 158 summarizes the major elements of potential toxicity.

In 2011, according to the University of Michigan survey, about 8 percent of high school seniors and about 3 percent of eighth graders reported having taken Ecstasy at some point in their lives. After a sharp rise in prevalence rates observed between 1998 and 2001 in these groups (peaking in 2001 at 12 percent and 5 percent, respec- tively), Ecstasy use has been on the decline, largely due to publicity about its adverse health effects. However, a worrisome trend began in 2005, with a decreasing number of high school seniors and eighth graders judging Ecstasy use to represent a great risk of harm. This trend will be watched carefully in coming years to predict whether a resurgence in the use of Ecstasy as a recreational drug may be on the horizon.41

Hallucinogens Related to Acetylcholine

Of the acetylcholine-related hallucinogens, some enhance the neurotransmitter and some inhibit it. Examples include Amanita muscaria mushrooms, atro- pine, scopolamine, and hyoscyamine.

Amanita muscaria The Amanita muscaria mushroom, also called the fly agaric mushroom because of its ability to lure and sedate flies and other insects, grows in the upper latitudes of the Northern Hemisphere, usually among the roots of birch trees. The mushroom has a bright red cap speck- led with white dots; the dancing mushrooms in Walt

Disney’s film Fantasia were inspired by the appearance (if not the hallucinogenic effects) of this fungus (see Figure 6.1b).

Amanita mushrooms are one of the world’s oldest intoxicants. Many historians hypothesize that this mush- room was the basis for the mysterious and divine sub- stance called soma that is celebrated in the Rig-Veda, one of Hinduism’s oldest holy books, dating from 1000 b.c. It is strongly suspected that amanita mush- rooms were used in Greek mystery cults and were the basis for the legendary “nectar of the gods” on Mount Olympus.42

The effects of amanita mushrooms can be lethal if dose levels are not watched very carefully. They pro- duce muscular twitching and spasms, vivid hallucina- tions, dizziness, and heightened aggressive behavior. It was briefly mentioned in Chapter 1 that Viking war- riors were reputed to have ingested amanita mushrooms before sailing off to battle. The drug-induced strength and savagery of these “berserk” invaders were so widely feared that a medieval prayer was written especially for protection from their attacks: “From the intolerable fury of the Norseman, O Lord, deliver us.”43

The Hexing Drugs and Witchcraft A number of natural plants contain chemicals that share a common feature: the ability to block the parasympa- thetic effects of acetylcholine in the body. The drugs with this ability, called anticholinergic drugs, produce specific physiological effects. The production of mucus in the nose and throat, and of saliva in the mouth, is reduced. Body temperature is elevated, sometimes to very high fever levels. Heart rate and blood pressure go up, and the pupils dilate considerably. Psychological effects include a feeling of delirium, confusion, and a loss of memory for events occurring during the drugged state.44 The amnesic property is one of the primary rea- sons for the minimal street appeal of these drugs.

The principal anticholinergic drugs are atropine, scopolamine (also called hyoscine), and hyoscyamine.

Amanita muscaria (a-ma-NEE-ta mus-CAR-ee-ah): A species of mushroom containing the hallucinogenic drug ibotenic acid.

atropine (AT-tro-peen): An anticholinergic hallucino- genic drug derived from the Atropa belladonna plant.

scopolamine (scoh-POL-ah-meen): An anticholiner- gic hallucinogenic drug. Also called hyoscine.

hyoscyamine (HEyE-oh-SEyE-eh-meen): An anticho- linergic hallucinogenic drug found in mandrake, hen- bane, and various species of the datura plant.

160 ■ Part Two Legally Restricted Drugs in Our Society

They are found in various combinations and relative amounts in a large number of psychoactive plants. Four of the better known ones are examined here.

■ Atropine is principally derived from the Atropa belladonna plant, also called deadly nightshade. Its lethal reputation is quite justified, since it is estimated that ingesting only a dozen or so berries is sufficient for death to occur. Through history, atropine has been associated with poisoning, either accidental or not. In the eleventh century, Scottish forces succeeded in destroying an opposing army (English or Scandi- navian, records are unclear) by atropine-adulterated shipments of meal. At lower, more benign dose lev- els, plant extracts can be applied to the eyes, causing the pupils to dilate. Egyptian and Roman women used this technique to enhance their beauty or at least improve their appearance. The term “belladonna” (“beautiful lady”) originates from this specific ap- plication. The psychological effects of atropine are generally associated with the anticholinergic effects of heart-rate acceleration, light-headedness, and general arousal.

■ The mandrake plant is an oddly shaped, potato-like plant with a long forked root that has traditionally been imagined to resemble a human body. In ancient times, mandrake was considered to have aphrodisiac properties. According to medieval folklore, mandrake plants supposedly shrieked when they were uprooted, understandably driving people mad.

Mandrake contains a combination of atropine, scopolamine, and hyoscyamine. Because low doses act as a depressant, mandrake has been used as a seda- tive-hypnotic drug to relieve anxiety and induce sleep. At higher doses, it produces bizarre hallucinations and muscular paralysis.

■ Henbane is a strong-smelling herb, native to wide- spread areas of the Northern Hemisphere, with purple-veined, yellowish flowers and hairy leaves. Its

English name, meaning “harmful to hens,” originates from the observation that henbane seeds were toxic to chickens and other birds. The lethal possibilities for henbane potions have been described by writers since the days of the Roman Empire. Hamlet’s father in Shakespeare’s play was supposedly murdered with henbane poison. Lower doses of henbane, however, have been used in a more benign way, as an anesthetic and painkiller. We now know that the predominant drugs in henbane are scopolamine and hyoscyamine.

■ Various species of the datura plant, containing a combination of atropine, scopolamine, and hyoscya- mine, grow wild in locations throughout the world. In the United States, one particular species, Datura stramonium, is called jimsonweed, a contraction of “Jamestown weed” (the name given to it by early American colonists). Consumption of the seeds or berries of jimsonweed produces hypnotic and hallu- cinogenic effects, together with disorientation, confu- sion, and amnesia. At high doses, jimsonweed is quite toxic. In recent years, there have been occasional reports of hospitalizations and even deaths among teenagers who have eaten jimsonweed seeds as an in- expensive way to get high.45

During medieval times, mixtures of deadly night- shade, mandrake, and henbane were responsible for the psychoactive effects of witches’ potions, producing a disastrous combination of physiological and psycho- logical effects. Satanic celebrations of the Black Mass centered on the ingestion of such brews. Atropine, in particular, produced a substantial elevation in arousal, probably leading to the feeling that the person was fly- ing (or at least capable of it), while the hallucinogenic effects enabled the person to imagine communing with the Devil. According to fourteenth-century reports, witches were described as preparing these mixtures as ointments and rubbing them on their bodies and on broomsticks, which they straddled while naked. The chemicals would have been easily absorbed through the skin and the membranes of the vagina. The consider- ably sanitized Halloween image of a witch flying on a broomstick has been with us ever since.46

Miscellaneous Hallucinogens

Three hallucinogens are referred to as miscellaneous hallucinogens because they do not have any chemical resemblance to serotonin, norepinephrine, or acetyl- choline. They are phencyclidine, ketamine, and Salvia divinorum.

Atropa belladonna (a-TROH-pah bEL-ah-DON-ah): A plant species, also called deadly nightshade, whose berries can be highly toxic. It is the principal source of atropine.

mandrake: A potato-like plant containing anticholin- ergic hallucinogenic drugs.

henbane: An herb containing anticholinergic halluci- nogenic drugs.

Datura stramonium (duh-TOOR-ah strah-MOH-nee- um): A species of the datura family of plants with hal- lucinogenic properties. In the United States, the plant is called jimsonweed.

Chapter 6 LSD and Other Hallucinogens ■ 161

Phencyclidine (PCP) Perhaps the most notorious of all the hallucinogens is phencyclidine (PCP), commonly known as angel dust. Technically, PCP is a synthetic depressant, and it was originally introduced in 1963 as a depressant drug by the Parke-Davis pharmaceutical company, under the brand name of Sernyl. It was marketed as a promis- ing new surgical anesthetic that had the advantage of not depressing respiration or blood pressure or causing heartbeat irregularities, as some other anesthetics do. In addition, PCP had a higher therapeutic ratio than many other anesthetics available at that time. By 1965, how- ever, it was withdrawn from human applications after reports that nearly half of all patients receiving PCP showed signs of delirium, disorientation, hallucinations, intense anxiety, or agitation. In 1979, PCP was classified as a Schedule II controlled substance and is still used as an anesthetic for animal surgery.

The weird combination of stimulant, depressant, and hallucinogenic effects makes PCP difficult to clas- sify. Some textbooks treat the discussion of PCP in a chapter on hallucinogens, as is done here, whereas others include it in a chapter on stimulants because some features of PCP intoxication resemble the effect of cocaine. A growing consensus of opinion has it that PCP should be described as a dissociative anesthetic hal- lucinogen, because it produces a feeling of being disso- ciated or cut off from one’s environment.

Acute Effects of PCP

PCP can be taken orally, intravenously, or by inhala- tion, but commonly it is smoked either alone or in combination with other drugs. Whatever its mode of administration, the results are extremely dangerous, with an unpredictability that far exceeds that of LSD or other hallucinogens. The symptoms may include manic excitement, depression, severe anxiety, sudden mood changes, disordered and confused thought, paranoid thoughts, and unpredictable aggression. Because PCP has analgesic properties as well, individuals taking the drug often feel invulnerable to threats against them and may be willing and able to withstand considerable pain. The mechanism behind PCP effects appears to be the blocking of a specific subtype of glutamate receptor in the brain (see Chapter 3).

Hallucinations also occur, but they are quite dif- ferent from the hallucinations experienced under the influence of LSD. There are no colorful images, no intermingling of sight and sound, no mysti- cal sense of being “one with the world.” Instead, a

prominent feature of PCP-induced hallucinations is the change in one’s body image. As one PCP abuser has expressed it:

The most frequent hallucination is that parts of your body are extremely large or extremely small. You can imagine yourself small enough to walk through a key hole, or you can be lying there and all of a sud- den you just hallucinate that your arm is twice the length of your body.47

Individuals under the influence of PCP also may stag- ger, speak in a slurred way, and feel depersonalized or

phencyclidine (PCP) (fen-SigH-klih-deen): A dis- sociative anesthetic hallucinogen that produces dis- orientation, agitation, aggressive behavior, analgesia, and amnesia. It has various street names, including angel dust.

Quick Concept Check 6.1

Understanding the Diversity of Hallucinogens Check your understanding of the psychological differ- ences among major hallucinogens by matching each hallucinatory experience (in the left column) with the hallucinogenic drug most apt to produce such effects (in the right column).

psychological experience hallucinogen

1. “The images I saw were Mexican designs as if they were created by an Aztec artist.”

2. “As I heard the bells, I also saw the vibrations move through the air.”

3. “The hallucinations were gone sixty minutes after they had started.”

4. “As I ate the red-topped mushrooms, I felt my mus- cles twitch. I could see vivid hallucinations.”

5. “I felt as if I were flying through the air.”

DMT

LSD

Atropa belladonna

psilocybin

mescaline

Amanita muscaria

Answers: 1. psilocybin 2. LSD, principally 3. DMT 4. Amanita muscaria 5. Atropa belladonna

162 ■ Part Two Legally Restricted Drugs in Our Society

detached from people around them. A prominent fea- ture is a prolonged visual stare, often called “doll’s eyes.”

The effects of PCP last from as little as a few hours to as long as two weeks, and they are followed by partial or total amnesia and dissociation from the entire experi- ence. Considering these bizarre reactions, it is not sur- prising that PCP deaths occur more frequently from the behavioral consequences of the PCP experience than from its physiological effects. Suicides, accidental or intentional mutilations, drownings (sometimes in very small amounts of water), falls, and threatening behavior leading to the individual being shot are only some of the possible consequences.48

Patterns of PCP Abuse

It is strange that a drug with so many adverse effects would be subject to deliberate abuse, but such is the case with PCP. Reports of PCP abuse began surfacing in 1967 among the hippie community in San Fran- cisco, where it became known as the PeaCe Pill. Word quickly spread that PCP did not live up to its name. Inexperienced PCP abusers were suffering the same bizarre effects as had the clinical patients earlier in the decade. By 1969, PCP had been written off as a garbage drug, and it dropped out of sight as a drug of abuse.

In the early 1970s, PCP returned under new street names and in new forms (Table 6.2). No longer a pill to be taken orally, PCP was now in powdered or liquid form. Powdered PCP could be added to parsley, mint, oregano, tobacco, or marijuana, rolled as a cigarette, and smoked. Liquid PCP could be used to soak leaf mixtures of all types, including manufactured cigarettes, which could then be dried and smoked. Many new users have turned to PCP as a way to boost the effects of marijuana. Making matters worse, as many as 120 different designer-drug variations of PCP have been developed in illicit laboratories around the country and the world. The dangers of PCP abuse, there- fore, are complicated by the difficulty in knowing whether a street drug has been adulterated with PCP and what ver- sion of PCP may be present. Unfortunately, the common practice of mixing PCP with alcohol or marijuana adds to the unpredictability of the final result.49

Ketamine Ketamine, a drug chemically similar to PCP, is also classified as a dissociative anesthetic hallucinogen. Like PCP, ketamine has a mixture of stimulant and

depressive properties, though its depressive effect is more extreme and does not last as long as that of PCP. Ketamine (brand name: Ketalar) was used as an emer- gency surgical anesthetic on the battlefield in Viet- nam as well as in standard hospital-based operations in which gaseous anesthetics could not be employed. It has also been used occasionally in short surgical proce- dures involving the head and neck or in the treatment of facial burns where it is not possible to use an anes- thetic mask. Adverse side effects, however, have limited its therapeutic use. These problems include unpredict- able and sometimes violent jerking and twitching of the body, as well as vivid and unpleasant dreams during and after surgery. During recovery, patients may experience hallucinations and feelings of disorientation. Delayed effects of ketamine, such as nightmares, have been reported to occur for weeks or longer after surgery.50

Ketamine abuse began to be reported in the 1980s. More recently, under the names “Special K” and “Vita- min K,” it has been included among current club drugs on the scene (see Chapter 1). Its popularity has increased among college students and patrons of dance clubs and all-night “rave” parties. Like PCP, ketamine produces a dreamlike intoxication, accompanied by an inability to move or feel pain. There are also experi- ences of dizziness, confusion, and slurred speech. As is the case with dissociative hallucinogens, ketamine pro- duces amnesia, in that abusers frequently cannot later

ketamine (KET-ah-meen): A dissociative anesthetic hallucinogen related to phencyclidine (PCP).

TAbLE 6.2

Street names for phencyclidine (PCP) and PCP-like drugs

PCP JET FuEL

angel dust sherms (derived from the reaction that it hits you like a Sherman tank)

monkey dust superkools

peep cyclones

supergrass zombie dust

killer weed ketamine

ozone special K

embalming fluid

rocket fuel

Note: In the illicit drug market, PCP and ketamine are fre- quently misrepresented and sold as mescaline, LSD, mari- juana, amphetamine, or cocaine.

Source: Updated from Milburn, H. T. (1991). Diagnosis and management of phencyclidine intoxication. American Family Physician, 43, 1293.

Chapter 6 LSD and Other Hallucinogens ■ 163

remember what has happened while under its influ- ence. The primary hazard of acute ketamine ingestion is the depression of breathing. Little is known, however, of the chronic effects of extended ketamine abuse over time, except that experiences of “flashbacks” have been reported. As with PCP, the effects of ketamine are asso- ciated with the blocking of specific glutamate receptors.

As with other club drugs that produce depressive effects on the central nervous system, there is the dan- gerous potential for ketamine to be abused as a “date- rape” drug. Women who may unwittingly take the drug can be rendered incapacitated, without the ability to recall the experience. In 1999, ketamine became classi- fied as a Schedule III controlled substance.51

Salvia divinorum The Mexican herb Salvia divinorum (commonly referred to as salvia) has a long tradition as a sha- manic treatment for diarrhea, headache, rheumatism, and abdominal discomfort. When smoked, chewed, or brewed as a tea, salvia produces intense visual

hallucinations (resembling the effect of psilocybin- containing mushrooms), laughter, and an “out of body,” dissociative experience. Its potency approaches that of LSD, but the effects are very short-lived. In one recent study of salvia users, 85 percent reported salvia effects lasting less than fifteen minutes.

Considerable media attention has been directed toward recreational use of salvia. At present, it has not been classified as a controlled substance under the fed- eral Controlled Substances Act. The DEA is currently pursuing the possibility of classification as a Schedule I drug, but until that occurs, salvia remains legally avail- able through numerous Internet web sites. In a grow- ing number of U.S. states and of countries around the world, salvia has been officially classified as an illicit drug, along with other hallucinogens.

According to the 2011 University of Michigan sur- vey, 6 percent of high school seniors reported using salvia in the past year. In a smaller sample of college students reporting in 2006, 23 percent of students had heard of salvia. About 7 percent had used it at some time in their lives, but the prevalence rate plummeted to less than 1 percent when respondents were asked whether they had used it in the last month. The “snapshots” that surveys of this kind reveal are twofold. First, it is virtually certain that extensive media attention has dramatically increased the level of awareness about salvia and its legal availability through Internet sources, so that most adoles- cents and young adults have heard about it. Second, it is likely that salvia may be attractive to those experiment- ing with a hallucinogen but not particularly attractive to chronic drug users. The particularly intense and unpre- dictable character of the salvia experience, as well as its very short duration, will be unpleasant to many. A major- ity of the first-time salvia users in the college sample said that they would not want to use it again.52

Salvia divinorum (SAL-via di-vi-NOR-um) or Salvia: A Mexican leafy herb with short-duration hallucinogenic effects.

Quick Concept Check 6.2

Understanding PCP Check your understanding of the effects of PCP by listing three major features of PCP intoxication that are significantly different from the effects of other hallucinogens.

Answer: Correct responses can include any of the follow- ing: analgesia, amnesia, prolonged stare, absence of synesthesia, absence of mysticism, unpredictable aggres- sion, extreme disorientation, feelings of being cut off from oneself or the environment.

Summary

A Matter of Definition ● Hallucinogens are, by definition, drugs that produce

distortions of perception and of one’s sense of real- ity. These drugs have also been called psychedelic (“mind-expanding”) drugs. In some cases, users of hal- lucinogens feel that they have been transported to a new reality.

● Other classes of drugs may produce hallucinations at high dose levels, but hallucinogens produce these effects at low or moderate dose levels.

Classifying Hallucinogens ● Hallucinogens can be classified into four basic

groups. The first three relate to the chemical similarity

164 ■ Part Two Legally Restricted Drugs in Our Society

between the particular drug and one of three major neurotransmitters: serotonin, norepinephrine, or acetylcholine.

● The fourth, miscellaneous group includes synthetic hallucinogens, such as PCP and ketamine, which bear little resemblance to any known neurotransmitter.

Lysergic Acid Diethylamide (LSD) ● LSD the best-known hallucinogenic drug, belongs to

the serotonin group. It is synthetically derived from ergot, a toxic rye fungus that has been documented as being responsible for thousands of deaths over the centuries.

● Albert Hofmann synthesized LSD in 1943, and Timo- thy Leary led the psychedelic movement that popular- ized LSD use in the 1960s.

● Although the LSD experience is often unpredictable, certain features are commonly observed: colorful hal- lucinations, synesthesia in which sounds often appear as visions, a distortion of perceptual reality, emotional swings, a feeling of timelessness, and an illusory sepa- ration of mind from body.

● It is now known that LSD effects are due to the stimu- lation of a subtype of brain receptors sensitive to sero- tonin, referred to as serotonin-2A receptors.

● In the early 1990s, there was a resurgence in LSD abuse, particularly among young individuals, a trend that began to reverse in 1997.

Facts and Fiction about LSD ● LSD does not produce psychological or physical de-

pendence and has only a slight chance of inducing a panic or psychotic state (provided that there is a sup- portive setting for the taking of LSD).

● LSD does not elevate one’s level of creativity. It does not damage chromosomes (though there remains a chance of birth defects if a woman ingests LSD when she is pregnant), and a relationship between LSD abuse and violent behavior has not been estab- lished. Flashback experiences, however, are potential hazards.

Psilocybin and Other Hallucinogens Related to Serotonin ● Other hallucinogens related to serotonin are psilocy-

bin, LAA, DMT, and harmine.

Hallucinogens Related to Norepinephrine ● Mescaline is chemically related to norepinephrine,

even though serotonin-2A receptors are responsible for its hallucinogenic effects.

● Two synthetic hallucinogens, DOM and MDMA, are variations of the amphetamine molecule. MDMA (Ecstasy) is currently a popular club drug, but re- search studies indicate that it poses serious health risks to the user.

Hallucinogens Related to Acetylcholine ● A number of anticholinergic hallucinogens, so named

because they diminish the effects of acetylcholine in the parasympathetic nervous system, have been in- volved in sorcery and witchcraft since the Middle Ages.

● These so-called hexing drugs contain a combina- tion of atropine, scopolamine, and/or hyoscyamine. Sources for such drugs include the deadly nightshade plant, mandrake roots, henbane seeds, and the datura plant family.

Miscellaneous Hallucinogens: Phencyclidine (PCP), Ketamine, and Salvia divinorum ● A dangerous form of hallucinogen abuse involves

PCP. Originally a psychedelic street drug in the 1960s, PCP quickly developed a reputation for pro- ducing a number of adverse reactions.

● PCP reappeared in the early 1970s in smokable forms, either alone or in combination with marijuana. Extremely aggressive tendencies, as well as behaviors resembling acute schizophrenia, have been associated with PCP intoxication.

● Ketamine is popular as a club drug that produces a dream-like intoxication, accompanied by an inability to move or feel pain. Like PCP, ketamine produces amnesia and a potentially hazardous depression in breathing.

● Salvia divinorum (or simply Salvia) is a Mexican leafy herb with short-duration hallucinogenic effects when smoked, chewed, or brewed as a tea. It is regarded by the DEA as a “drug of concern,” considering its grow- ing popularity as a recreational drug, although it is not presently classified as a Schedule I drug under the Controlled Substances Act.

Chapter 6 LSD and Other Hallucinogens ■ 165

Key Terms

Amanita muscaria, p. 159 Atropa belladonna, p. 160 atropine, p. 159 bufotenine, p. 155 cyanosis, p. 155 Datura stramonium, p. 160 dimethyltryptamine (DMT),

p. 155

DOM, p. 156 ergot, p. 146 ergotism, p. 146 hallucinogens, p. 144 harmine, p. 156 henbane, p. 160 hyoscyamine, p. 159 ketamine, p. 162

lysergic acid amide (LAA), p. 155

lysergic acid diethylamide (LSD), p. 144

mandrake, p. 160 MDMA (Ecstasy), p. 157 mescaline, p. 156 peyote, p. 156

phencyclidine (PCP), p. 161

psilocin, p. 154 psilocybin, p. 154 Salvia divinorum (Salvia),

p. 163 scopolamine, p. 159 synesthesia, p. 150

Endnotes

1. Hofmann, A. (1980). LSD: My problem child. New York: McGraw-Hill, p. 17.

2. Ibid., pp. 17–18. 3. Ibid., p. 19. 4. Brophy, J. J. (1985). Psychiatric disorders. In M. A.

Krupp, M. J. Chatton, and D. Werdegar (Eds.), Current medical diagnosis and treatment. Los Altos, CA: Lange Medical Publications, p. 674.

5. Mann, J. (1992). Murder, magic, and medicine. New York: Oxford University Press, pp. 41–51.

6. Fuller, J. G. (1968). The day of St. Anthony’s fire. New York: Macmillan, preface.

7. Leary, T. (1973). The religious experience: Its production and interpretation. In G. Weil, R. Metzner, and T. Leary (Eds.), The psychedelic reader. Secaucus, NJ: Citadel Press, p. 191.

8. Lattin, D. (2010). The Harvard psychedelic club. New York: HarperCollins. Lee, M. A., and Shlain, B. (1985). Acid dreams: The complete social history of LSD. New York: Grove Weidenfeld, pp. 71–118.

9. Greenfield, R. (2006). Timothy Leary: A biography. New York: J.H. Silberman Books/Harcourt. Leary, T. (1968). High priest. New York: New American Library, p. 46. Manchester, W. R. (1974). The glory and the dream: A narrative history of America, 1932–1972. Boston: Little, Brown, p. 1362.

10. Grinspoon, L., and Bakalar, J. B. (1979). Psychedelic drugs reconsidered. New York: Basic Books, p. 68.

11. Brown, F. C. (1972). Hallucinogenic drugs. Springfield, IL: C.C. Thomas, pp. 46–49. Goode, E. (2008). Drugs and American society (7th ed.). New York: McGraw-Hill, p. 260.

12. Schuckit, M. A. (2006). Drug and alcohol abuse: A clini- cal guide to diagnosis and treatment (6th ed.). New York: Springer, pp. 211–214.

13. Jacobs, M. R., and Fehr, K. O’ B. (1987). Drugs and drug abuse: A reference text (2nd ed.). Toronto: Addiction Research Foundation, p. 345. Substance Abuse and Mental Health Services Administration (2013). Drug Abuse Warning Network, National estimates of drug- related emergency department visits 2004–2011. Rockville, MD: Substance Abuse and Mental Health Services Administration, Excel files.

14. Brophy, Psychiatric disorders. Jacobs and Fehr, Drugs and drug abuse, pp. 337–347.

15. First, third, fourth, and fifth quotations from Goode, Drugs and American society, pp. 261–263. Second, sixth, seventh, and eighth quotations from Snyder, S. H. (1986). Drugs and the brain. New York: Freeman, pp. 180–181.

16. Aghajanian, G. K., and Marek, G. J. (1999). Serotonin and hallucinogens. Neuropsychopharmacology, 21 (Suppl. 2), 16S–23S. Gresch, P. J.; Smith, R. L.; Barrett, R. J.; and Sanders-Bush, E. (2005). Behavioral tolerance to lysergic acid diethylamide is associated with reduced serotonin-2A receptor signaling in rat cortex. Neuropsychopharmacol- ogy, 30, 1693–1702. Julien, R. M. (2005). A primer of drug action (10th ed.). New York: Worth, p. 602.

17. Goode, Drugs and American society, p. 259. 18. Brands, B.; Sproule, B.; and Marshman, J. (1998). Drugs

and drug abuse: A reference text. Toronto, Canada: Addiction Research Foundation, p. 328. Henderson, L. A., and Glass, W. J. (Eds.) (1994). LSD: Still with us after all these years. New York: Lexington Books. Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2012). Monitoring the Future: National survey results on drug use, 1975–2011. Vol. I: Secondary school students 2011. Ann Arbor, MI: Institute for Social Research, The University of Michigan, Table 2-1.

19. Goode, Drugs and American society, pp. 265–266. 20. Ibid., p. 266. 21. Cohen, S. (1960). Lysergic acid diethylamide: Side

effects and complications. Journal of Nervous and Mental Diseases, 130, 30–40. Levine, J., and Ludwig, A. M. (1964). The LSD controversy. Comprehensive Psychiatry, 5 (5), 314–321.

22. Wells, B. (1974). Psychedelic drugs: Psychological, medical, and social issues. New York: Jason Aronson, pp. 170–188.

23. Cohen, M. M., and Marmillo, M. J. (1967). Chromo- somal damage in human leukocytes induced by lysergic acid diethylamide. Science, 155, 1417–1419.

24. Dishotsky, N. I.; Loughman, W. D.; Mogar, R. E.; and Lipscomb, W. R. (1971). LSD and genetic damage. Science, 172, 431–440. Grinspoon and Bakalar, Psychedelic drugs reconsidered, pp. 188–191.

25. Brown, Hallucinogenic drugs, pp. 61–64. Wells, Psychedelic drugs, pp. 104–109.

26. Abraham, H. D. (1983). Visual phenomenology of the LSD flashback. Archives of General Psychiatry, 40,

166 ■ Part Two Legally Restricted Drugs in Our Society

884–889. Schlaadt, R. G., and Shannon, P. T. (1994). Drugs: Use, misuse, and abuse. Englewood Cliffs, NJ: Prentice-Hall, p. 273.

27. Halpern, J. H., and Pope, H. G. (1999). Do hallucino- gens cause residual neuropsychological toxicity? Drugs and Alcohol Dependence, 53, 247–256.

28. Knudsen, K. (1964). Homicide after treatment with lysergic acid diethylamide. Acta Psychiatrica Scandi- navica, 40 (Suppl. 180), 389–395.

29. Metzner, R. (1998). Hallucinogenic drugs and plants in psychotherapy and shamanism. Journal of Psychoactive Drugs, 30, 333–341.

30. Hofmann, LSD, p. 112. 31. Brown, Hallucinogenic drugs, pp. 81–88. 32. Johnston, O’Malley, Bachman, and Schulenberg,

Monitoring the Future, Table 9-8., Vollenweider, Franz X.; Vollenweider-Scherpenhuyzen, M. F. I.; Babler, A.; Vogel, H.; and Hell, D. (1998). Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport, 9, 3897–3902.

33. Hofmann, LSD, pp. 119–127. Schultes, Richard E., and Hofmann, A. (1979). Plants of the gods: Origins of hal- lucinogenic use. New York: McGraw-Hill, pp. 158–163.

34. Brands, Sproule, and Marshman, Drugs and drug abuse, pp. 512–513.

35. Frecska, E.; White, K. D.; and Luna, L. E. (2003). Effects of Amazonian psychoactive beverage ayuhuasca on bin- ocular rivalry: Interhemispheric switching or interhemi- spheric fusion? Journal of Psychoactive Drugs, 35, 367–374. Grinspoon and Bakalar, Psychedelic drugs reconsidered, pp. 14–15. Trichter, S.; Klimo, J.; and Krippner, S. (2009). Changes in spirituality among ayahuasca ceremony novice participants. Journal of Psychoactive Drugs, 41, 121–134.

36. Ibid., pp. 20–21. Hollister, L. E., and Sjoberg, B. M. (1964). Clinical syndromes and biochemical alterations following mescaline, lysergic acid diethylamide, psilo- cybin, and a combination of the three psychotomimetic drugs. Comprehensive Psychiatry, 5, 170–178.

37. Jacobs, B. L. (1987). How hallucinogenic drugs work. American Scientist, 75, 386–392.

38. Brecher, Edward, and the editors of Consumer Reports (1972). Licit and illicit drugs. Boston: Little, Brown, pp. 376–377.

39. Carey, B. (2012, November 20). A “party drug” may help the brain cope with trauma. New York Times, pp. D1, D6. Metzner, Hallucinogenic drugs and plants. Schmidt, C. J. (1987). Psychedelic amphetamine, meth- ylendioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics, 240, 1–7.

40. Boils, K. I. (1999). Memory impairment in abstinent MDMA (“Ecstasy”) users. Journal of the American Medi- cal Association, 281, 494. Leshner, A. I. (2002). Ecstasy abuse and control: Hearing before the Senate Subcom- mittee on Governmental Affairs—July 30, 2001. State- ment for the record. Journal of Psychoactive Drugs, 34, 133–135. Vollenweider, F. X.; Liechti, M. E.; Gamma, A.; Greer, G.; and Geyer, M. (2002). Acute psychologi- cal and neurophysiological effects of MDMA in humans.

Journal of Psychoactive Drugs, 34, 171–184. Wiegand, T.; Thai, D.; and Benowitz, N. (2008). Medical conse- quences of the use of hallucinogens: LSD, mescaline, PCP, and MDMA (“Ecstasy”). In J. Brick (Ed.), Hand- book of medical consequences of alcohol and drug use (2nd ed.). New York: Routledge, pp. 473-490.

41. Cloud, J. (2000, June 5). The lure of Ecstasy. Time, pp. 62–68. Feuer, A. (2000, August 6). Distilling the truth in the Ecstasy buzz. New York Times, pp. 25, 28. Johnston, O’Malley, Bachman, and Schulenberg, Monitoring the Future, Table 2-1. Martins, Silvia, S.; Mazzotti, G.; and Chilcoat, H. D. (2005). Trends in Ecstasy use in the United States from 1995 to 2001: Comparison with mari- juana users and association with other drug use. Experi- mental and Clinical Psychopharmacology, 13, 244–252.

42. Wasson, R. G. (1968). Soma: Divine mushroom of immortality. New York: Harcourt, Brace and World.

43. Cohen, S. (1964). The beyond within: The LSD story. New York: Atheneum, p. 17.

44. Ramachandran, V. S., and Hubbard, E. M. (2003, May). Hearing colors, tasting shapes. Scientific American, pp. 52–59.

45. Clark, Jason D. (2005). The roadside high: Jimson weed toxicity. Air Medical Journal, 24, 234–237. Schultes and Hofmann, Plants of the gods, pp. 35, 106–111.

46. Mann, J. (1992). Murder, magic, and medicine. New York: Oxford University Press, pp. 79–82. Schultes and Hofmann, Plants of the gods, pp. 86–91.

47. James, J., and Andresen, E. (1979). Sea-Tac and PCP. In H. V. Feldman, M. H. Agar, and G. M. Beschner (Eds.), Angel dust: An ethnographic study of PCP users. Lexington, MA: Lexington Books, p. 133.

48. Grinspoon and Bakalar, Psychedelic drugs reconsidered, pp. 32–33. Petersen, R. C., and Stillman, R. C. (1978). Phencyclidine: An overview. In R. C. Petersen and R. C. Stillman (Eds.), Phencyclidine (PCP) abuse: An appraisal (NIDA Research Monograph 21). Rockville, MD: National Institute on Drug Abuse, pp. 1–17. Robbins, Hallucinogens, pp. 12–14. Seeman, P.; Ko, F.; and Tallerico, T. (2005). Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics. Molecular Psychiatry, 10, 877–883.

49. Trends in PCP-related emergency department visits (2004, January). The DAWN Report, pp. 1–4.

50. Brands, Sproule, and Marshman, Drugs and drug abuse, pp. 523–525.

51. Ibid. Feds classify ketamine as controlled substance (1999, August 2). Alcoholism and Drug Abuse Weekly, p. 7.

52. Braiker, B. (2008, May 19). Old herb, new controversy. Newsweek, pp. 40–41. González, D.; Riba, J.; Bouso, J. C.; Gómez-Jarabo, G.; et al. (2006). Pattern of use and subjec- tive effects of Salvia divinorum among recreational users. Drug and Alcohol Dependence, 85, 157–162. Johnston, O’Malley, Bachman, and Schulenberg, Monitoring the Future, Table 2-2. Julien, A primer of drug action, p. 619. Khey, D.N.; Miller, B.L.; and Griffin, O.H. (2008). Salvia divinorum use among a college student sample. Journal of Drug Education, 38, 297–306.

167

C h a p t e r

7 Marijuana

The sprawled body of a young girl lay crushed on the side-

walk the other day after a plunge from the fifth story of a

Chicago apartment house. Everyone called it suicide, but

actually it was murder. The killer was a narcotic known to

America as marijuana, and to history as hashish. It is a

narcotic used in the form of cigarettes, comparatively

new to the United States and as dangerous as a coiled

rattlesnake. . . .

How many murders, suicides, robberies, criminal as-

saults, holdups, burglaries, and deeds of maniacal insan-

ity it causes each year, especially among the young, can

be only conjectured. . . .

That youth has been selected by the peddlers of this

poison as an especially fertile filed makes it a problem of

serious concern to every man and woman in America.

—Harry J. Anslinger, Commissioner, Federal Bureau of Narcotics, in the opening of an article

in the widely-read periodical, The American Magazine, published in July 1937.1

After you have completed this chapter, you should have an understanding of

▶ The history of marijuana and other cannabis products

▶ Acute effects of marijuana

▶ The neural basis for the effects of marijuana

▶ Long-term effects of marijuana

▶ The amotivational syndrome and the gateway theory

▶ Patterns of marijuana smoking

▶ The medical marijuana controversy

▶ Marijuana decriminalization and legalization

168 ■ Part Two Legally Restricted Drugs in Our Society

It is fair to say that few other drugs have been so polit- icized in the history of the twentieth century. Marijuana has been frequently praised by one side, or (judging from the Anslinger quotation) demonized by the other, on the basis of emotionally charged issues rather than an objective view of research data, and sometimes with little regard for the facts. The pro-marijuana faction has tended to dismiss or downplay reports of potential dan- gers and to emphasize the benefits; the anti-marijuana faction has tended to do the opposite, arguing that mar- ijuana should continue to be classified by the U.S. fed- eral government as a Schedule I controlled substance, along with heroin and LSD. It is the drug that everyone brings up when debating the successes or failures of the decades-long war on drugs. Marijuana has often been regarded, in cultural terms, as a reflection of an indi- vidual’s attitude toward the establishment. This makes it even more critical that we look at the effects of mari- juana as dispassionately as possible.

Think of Cannabis sativa, known to the general public as the marijuana plant, as a scrawny weed with an attitude. Whether it is hot or cold, wet or dry, can- nabis will grow abundantly from seeds that are unbeliev- ably hardy and prolific. Under ordinary circumstances, it needs little or no cultivation. A handful of cannabis seeds, tossed on the ground and pressed in with one’s foot, will usually anchor and become plants. Its roots devour whatever nutrients there are in the soil, as histo- rian Ernest Abel has expressed it, “like a vampire suck- ing the life blood from the earth.”2

Indeed, marijuana has managed to grow in some unorthodox places. It can be found growing wild in median strips of interstate highways and in ditches alongside country roads, much to the chagrin of local authorities. Its legendary hardiness has spawned urban myths over the years. One of them is the existence of the so-called Manhattan Silver strain, supposedly growing to this day in underground New York sewers, after hav- ing been hastily flushed down a toilet during a police raid in the 1960s.3

The pharmacological effects of marijuana show something of an independent nature as well. When we consider a category for marijuana, we are faced with an odd assortment of unconnected properties, making it difficult to place marijuana within a traditional classifi- cation of psychoactive drugs. Marijuana produces some excitatory effects, but it is not generally regarded as a stimulant. It produces some sedative effects, but a user faces no risk of slipping into a coma or dying. It pro- duces mild analgesic effects, but it is not related chemi- cally to opioid drugs. It produces hallucinations at high doses, but its structure does not resemble that of LSD or any other drug formally categorized as a hallucinogen (see Chapter 6). Marijuana is clearly a drug in a league of its own.

A Matter of Terminology

Although marijuana (sometimes spelled marihuana) is commonly referred to as a synonym for “cannabis,” the two terms need to be differentiated. Cannabis is the shortened botanical term for the hemp plant Cannabis sativa. With a potential height of about eighteen feet, cannabis has sturdy stalks, four-cornered in cross-section, that have been commercially valu- able for thousands of years in the manufacture of rope, twine, shoes, sailcloth, and containers of all kinds. Pots made of hemp fiber discovered at archaeological sites in China date the origins of cannabis cultivation as far back as the Stone Age. It is arguably the oldest culti- vated plant not used for food.4

Spaniards brought cannabis to the New World in 1545, and English settlers brought it to Jamestown, Virginia, in 1611, where it became a major commer- cial crop, along with tobacco. Like other eighteenth- century farmers in the region, George Washington grew cannabis in the fields of his estate at Mount

Cannabis sativa (CAN-uh-bus sah-TEE-vah): A plant species, commonly called hemp, from which marijuana and hashish are obtained.

by the numbers . . .

107,842,000 Estimated number of Americans who reported in 2011 that they had smoked marijuana sometime in their lifetime.

18,071,000 Estimated number of Americans who reported in 2011 that they had smoked marijuana in the previous month.

18 Number of U.S. states in 2012 that have authorized marijuana smok- ing for the relief of pain and dis- comfort or for the control of nausea and weight loss, when prescribed by a physician.

Source: Substance Abuse and Mental Health Services Administration (2012). Results from the 2011 National Survey on Drug Use and Health. Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Administration, Table 1.1A.

Chapter 7 Marijuana ■ 169

Vernon. Entries in his diary indicate that he main- tained a keen interest in the improvement of strains of cannabis, but there is no reason to believe he was interested in anything more than producing a better- quality rope.

Marijuana, however, is obtained not from the stalks of the cannabis plant but from its serrated leaves. The key psychoactive factor is contained in a sticky substance, or resin, that accumulates on these leaves. Depending on the growing conditions, cannabis will produce either a greater amount of fiber or a greater amount of resin. In a cool, humid climate, such as North America, less resin is produced, but the fiber is stronger and more durable. In a warmer, less humid climate—such as North Africa—the fiber content is weak, but so much resin is produced that the plant looks as if it is covered with dew. Therefore, depending on environmental factors, you are getting a stronger rope or a stronger high.5

As many as eighty separate chemical compounds, called cannabinoids, have been identified from can- nabis resin. Among these, the chief psychoactive com- pound and the active ingredient that produces the intoxicating effects is delta-9-tetrahydrocannabinol (THC). The isolation and identification of THC in 1964 was a major step toward understanding the effects on the brain of marijuana and similar preparations obtained from Cannabis sativa.

Knowing these facts, we can categorize various forms of cannabis products in terms of their origin within the cannabis plant and resulting THC concen- tration. The first and best known of these products, marijuana, consists of leaves and occasionally flowers of the cannabis plant that are first dried and then shred- ded. During the 1960s and 1970s, the typical THC con- centration of street marijuana imported from Mexico was about 1 to 2 percent. Since the early 1990s, how- ever, THC concentrations have steadily risen to about 10 percent, primarily because of advanced outdoor and indoor cultivation methods. Marijuana, smoked as a cigarette, is the form of cannabis most familiar to North Americans.

A more potent form of marijuana is obtained by cultivating only the unpollinated, or seedless, portion of the cannabis plant. Without pollination, the canna- bis plant grows bushier, the resin content is increased, and a greater THC concentration, up to 15 percent, is achieved. This form is called sinsemilla, from the Span- ish meaning “without seed.”

Another cannabis product, hashish, is achieved when the resin itself is scraped from cannabis leaves and then dried. Either smoked by itself or in combination

with tobacco, hashish can have a THC concentration as high as 24 percent. The most potent forms of can- nabis are hashish oil and hashish oil crystals, produced by boiling hashish in alcohol or some other solvent and filtering out the alcohol, which leaves a residue with a THC concentration ranging from 15 to 60 percent.6

cannabinoids (can-NAB-ih-noids): Any of several dozen active substances in marijuana and other cannabis products.

delta-9-tetrahydrocannabinol (THC) (DEL-tah-9-TEH- trah-HIGH-dro-CAN-a-bih-nol): The active psychoac- tive ingredient in marijuana and hashish.

marijuana: The most commonly available psycho- active drug originating from the cannabis plant. The THC concentration ranges from approximately 1 to 6 percent. Also spelled marihuana.

sinsemilla (SIN-sih-MEE-yah): A form of marijuana obtained from the unpollinated or seedless portion of the cannabis plant. It has a higher THC concentration than regular marijuana, as high as 15 percent.

hashish (hah-SHEESH): A drug containing the resin of cannabis flowers. The THC concentration ranges from approximately 8 to 14 percent.

hashish oil: A drug produced by boiling hashish, leaving a potent psychoactive residue. The THC concentration ranges from approximately 15 to 60 percent.

hashish oil crystals: A solid form of hashish oil.

A Mexican harvester gathers his crop of Cannabis sativa, later to be processed into marijuana or hashish.

170 ■ Part Two Legally Restricted Drugs in Our Society

The History of Marijuana and Hashish

The first direct reference to a cannabis product as a psy- choactive agent dates from 2737 b.c. in the writings of the mythical Chinese emperor Shen Nung. The focus was on its powers as a medication for rheumatism, gout, malaria, and (strangely enough) absent-mindedness. Mention was made of its intoxicating properties, but the medicinal possibilities evidently were considered more important. In India, however, its use was clearly recre- ational. The most popular form, in ancient times as well as in the present day, can be found in a syrupy liquid made from cannabis leaves called bhang, with a THC potency usually equal to that of a marijuana joint in the United States.7

The Muslim world also grew to appreciate the psy- choactive potential of cannabis, encouraged by the fact that, in contrast to its stern prohibition of alcohol con- sumption, the Koran did not specifically ban its use. It was here, in a hot, dry climate conducive to maximizing the resin content of cannabis, that hashish was born, and its popularity spread quickly during the twelfth century from Persia (Iran) in the east to North Africa in the west.

Hashish in the Nineteenth Century In Western Europe, knowledge about hashish or any other cannabis product was limited until the beginning of the nineteenth century. Judging from the decree issued by Pope Innocent VIII in 1484 condemning witchcraft and the use of hemp in the Black Mass, we can assume that the psychoactive properties of cannabis were known by at least some portions of the population. Nonetheless, there is no evidence of widespread use.

By about 1800, however, cannabis had become more widely known and was the subject of a popular craze. One reason was that French soldiers who had served in Napoleon’s military campaigns in Egypt brought hash- ish back with them to their homes in France. Another reason was a wave of romanticism that swept Europe, including an increased interest in exotic stories of the East, notably the Arabian Nights and the tales of Marco Polo, which contained references to hashish.

In Paris during the 1840s, a small group of promi- nent French artists, writers, and intellectuals formed the Club des Hachichins (“Club of the Hashish-Eaters”),

where they would gather, in the words of their leader, “to talk of literature, art, and love” while consuming hashish. The recipe consisted of a concentrated can- nabis paste mixed with butter, sweeteners, and flavor- ings such as vanilla and cinnamon. Members included Victor Hugo, Alexandre Dumas, Charles Baudelaire, Eugéne Delacroix, and Honoré de Balzac.

Marijuana and Hashish in the Twentieth Century Chances are that anyone living in the United States at the beginning of the twentieth century would not have heard of marijuana, much less hashish. By 1890, cot- ton had replaced hemp as a major cash crop in south- ern states, although cannabis plants continued to grow wild along roadsides and in the fields. Some patent

bhang: A liquid form of marijuana popular in India.

A merchant sits outside his bhang shop in North India. Bhang ki thandai is a popular cold drink prepared with bhang com- bined with almonds, spices, milk, and sugar. Bhang lassi, a mixture of bhang and iced yogurt, is another popular drink. It is traditional for many Hindus to drink bhang during religious festivals, particularly in Bengal during the Kali Puja (Festival of Kali, the Mother Goddess).

Chapter 7 Marijuana ■ 171

medicines during this era contained marijuana, but it was a small percentage compared with the number con- taining opium or cocaine (see Chapter 1).8

It was not until the 1920s that marijuana smoking began to be a social phenomenon. Some historians have related the appearance of marijuana as a recre- ational drug to societal changes brought on by Prohi- bition (see Chapter 8), when it was suddenly difficult to obtain good-quality liquor at affordable prices. Rec- reational use was taken up primarily by jazz musicians and people in show business. “Reefer songs” became the rage of the jazz world; even the mainstream clarinet- ist and bandleader Benny Goodman had his popular hit “Sweet Marihuana Brown.” Marijuana clubs, called tea pads, sprang up in the major cities; more than five hun- dred were estimated to have opened in Harlem alone, outnumbering the speakeasies where illegal alcohol was dispensed. These marijuana establishments were largely tolerated by the authorities because at that time mari- juana was not illegal and patrons showed no evidence of making a nuisance of themselves or disturbing the com- munity. In the culture of the time, marijuana was not considered a threat at all.9

The Anti-Marijuana Crusade The picture started to change by the end of the 1920s and early 1930s. Even though millions of people had never heard of the marijuana, much less smoked it, the drug suddenly became widely known as a “killer weed.” An intense anti-marijuana media campaign in print and in the movies (see Chapter 2), orchestrated by the Federal Bureau of Narcotics (FBN), had succeeded in convincing the American public that marijuana was a pestilence singlehandedly destroying a generation of American youth. These efforts, however, could not have been as successful as they were without a significant demographic change occurring in American society at the time. The practice of smoking marijuana and the cultivation of cannabis plants for that purpose had been filtering slowly into the United States since 1900 as a result of the migration of Mexican immigrants. They entered the country through towns along the Mexican border and along the Gulf Coast. In Mexican commu- nities, marijuana was a casual part of Mexican life, a mild euphoriant, and often a folk remedy for headaches.

Once in the United States, however, these immi- grant communities were met with considerable hostility, and the smoking of an alien and foreign-sounding sub- stance did not smooth their reception, particularly as their numbers increased. In effect, it would be a social rerun of the Chinese-opium panic of the 1870s (see Chapter 5)

but with the Mexicans on the receiving end. Unsubstan- tiated rumors about the violent behavioral consequences of marijuana smoking among Mexicans began to spread. In addition, social and economic upheavals during the Depression made it particularly convenient to vent frus- trations on an immigrant group perceived as competing for a dwindling number of American jobs and straining an already weak economy. Anti-marijuana-themed mov- ies with provocative titles such as Reefer Madness and Marihuana: Weed with Roots in Hell were produced and distributed during the late 1930s and early 1940s with the encouragement of the FBN.

Considering the mounting hysteria against marijuana smoking and cannabis use in general during this period, it is not surprising that the Marijuana Tax Act of 1937 had little difficulty gaining support in Congress. As with the Harrison Act of 1914, the regulation of marijuana was accomplished indirectly. The act did not ban marijuana; it merely required everyone connected with marijuana,

This advertising poster for the 1942 film Devil’s Harvest depicted the supposed evils of smoking marijuana.

172 ■ Part Two Legally Restricted Drugs in Our Society

from growers to buyers, to pay a tax. It was a deceptively simple procedure that, in effect, made it virtually impossi- ble to comply with the law. In the absence of compliance, a person was in violation of the act and therefore subject to arrest. It was the state’s responsibility to make possession of marijuana or any other product of Cannabis sativa illegal. Shortly after the tax act of 1937 was imposed, all of the states adopted a uniform law that did just that.

The official stance of the federal government contin- ued to be that marijuana smoking was tied to antisocial behavior. Harry Anslinger, FBN director, wrote in 1953:

Those who are accustomed to habitual use of the drug are said eventually to develop a delirious rage after its administration during which they are tem- porarily, at least, irresponsible and prone to com- mit violent crimes. . . . Much of the most irrational juvenile violence and killing that has written a new chapter of shame and tragedy is traceable directly to this hemp intoxication.10

Over time, the “pharmacological violence” theory (see Chapter 2) would fade into oblivion, in the absence of any evidence to support it. In its place, a new concep- tualization of marijuana smoking would be introduced by the FBN: the gateway theory. According to this idea, marijuana was dangerous because its abuse would lead to the abuse of heroin, cocaine, or other illicit drugs. This gateway hypothesis will be closely examined later in the chapter.

The severity of criminal penalties for involve- ment with marijuana steadily increased. State judges frequently had the option of sentencing a marijuana seller or user to life imprisonment. In Georgia, a second offense of selling marijuana to a minor could be punish- able by death.

Ironically, in 1969, more than three decades after its passage, the U.S. Supreme Court ruled the 1937 Mari- juana Tax Act unconstitutional precisely because mari- juana possession was illegal. The argument was made that requiring a person to pay a tax (and that was all that the 1937 act concerned) in order to possess an ille- gal substance amounted to a form of self-incrimination, which would violate that person’s rights under the Fifth Amendment to the Constitution. The case in question here was brought to the high court by none other than Timothy Leary (see the Portrait in Chapter 6), and the court’s decision succeeded in overturning a marijuana conviction judged against him.11

Challenging Old Ideas about Marijuana Prior to 1960, arrests and seizures for possession of mari- juana were relatively rare and attracted little or no pub- lic attention. The social consensus was that marijuana was a drug that could be comfortably associated with, and isolated to, ethnic and racial minorities. It was rela- tively easy for most Americans to avoid the drug entirely. In any event, involvement with marijuana during the 1950s was a deviant act, in an era when there was little tolerance for personal deviance.

By the mid-1960s, this consensus began to dissolve. Marijuana smoking suddenly was an attraction on the campuses of U.S. colleges and universities, affecting a wide cross section of the nation. Strangely enough, the bizarre effects depicted in the anti-marijuana movies failed to occur! At the same time, the experimental use of drugs, particularly marijuana, by young people set the stage for a wholesale questioning of what it meant to respect authority, on an individual as well as a gov- ernmental level. We will turn to the more recent issues of medical marijuana and marijuana decriminalization later in the chapter.

Acute Effects of Marijuana

In the United States, THC is usually ingested by smok- ing a hand-rolled marijuana cigarette referred to as a reefer, or, more commonly, a joint. Exactly how much THC is administered depends on the specific THC concentration level in the marijuana (often referred to as its quality), how deeply the smoke is inhaled into the lungs, and how long it is held in the lungs before being exhaled. In general, an experienced smoker will consume more THC than a novice smoker by virtue of being able to inhale more deeply and hold the mari- juana smoke in his or her lungs longer, for twenty-five seconds or more, thus maximizing THC absorption into the bloodstream.

The inhalation of any drug into the lungs produces extremely rapid absorption, as noted in earlier chapters, and marijuana is no exception. In the case of THC, effects are felt within seconds. Peak levels are reached in the blood within ten minutes and start to decline shortly afterward. Behavioral and psychological effects generally last from two to three hours. At this point, low levels of THC linger for several days because they are absorbed into fatty tissue, and excretion from fatty tissue is notoriously slow.12

reefer: A marijuana cigarette.

joint: A marijuana cigarette.

Chapter 7 Marijuana ■ 173

One implication arising from a slow elimination rate is that the residual THC, left over from a previous administration, can intensify the effect of marijuana on a subsequent occasion. In this way, regular marijuana smokers often report a quicker and more easily obtained high, achieved with a smaller quantity of drug, than more intermittent smokers.13

It is also important to see the implication of slow marijuana elimination with regard to drug testing. Urine tests for possible marijuana abuse typically mea- sure levels of THC metabolites (broken-down remnants of THC); because of the slow biotransformation of mar- ijuana, these metabolites are detectable in the urine even when the smoker no longer feels high or shows any behavioral effects. Metabolites can remain in the body for several days after the smoking of a single joint and for several weeks later if there has been chronic marijuana smoking. Some tests are so sensitive that a positive level for marijuana can result from passive inhalation of marijuana smoke–filled air in a closed environment, even though the THC levels in these cases are substantially below levels that result from active smoking. The bottom line is that marijuana test- ing procedures generally are unable to indicate when marijuana has been smoked (if it has been smoked at all), only that exposure to marijuana has occurred (see Chapter 12).14

Acute Physiological Effects Immediate physiological effects after smoking mari- juana are relatively minor. It has been estimated that a human would need to ingest a dose of marijuana that was from twenty thousand to forty thousand times the effective dose before death would occur.15 Nonetheless, there is a dose-related increase in heart rate during early stages of marijuana ingestion, up to 160 beats per minute when dose levels are high. Blood pressure either increases, remains the same, or decreases, depending primarily on whether the individual is standing, sitting, or lying down.16 A dilation of blood vessels on the cornea resulting in bloodshot eyes peaks about an hour after smoking a joint. Frequently there is a drying of the mouth and an urge to drink.

Other physiological reactions are inconsistent, and at least part of the inconsistency can be attributed to cultural and interpersonal influences. For example, the observation that marijuana smoking makes you feel extremely hungry and crave especially sweet things to eat (often referred to as “having the munchies”) gener- ally holds true in studies of North Americans but not

for Jamaicans, who consider marijuana an appetite suppressant.

Likewise, North Americans often report enhanced sexual responses following marijuana use, whereas in India marijuana is considered a sexual depressant. These reactions, being subjective in nature, can very well be influenced in one direction or the other by the mind-set (expectations) of the marijuana smoker going into the experience. A good example is the effect on sexual responses. If you believe that marijuana turns you on sexually, the chances are that it will.

Although expectations undoubtedly play a promi- nent role here, we should be aware of the possibility that varying effects also may be due to differences in the THC concentration of the marijuana being smoked. In the case of sexual reactivity, studies of male marijuana smokers have shown that low-dose marijuana tends to enhance sexual desire, whereas high-dose marijuana tends to depress it, even to the point of impotence. It is quite possible that the enhancement results from a brief rise in the male sex hormone testosterone and that the depression results from a rebound effect that lowers testosterone below normal levels. Typically, the THC concentration in India is higher than that in North America. As a result, we would expect different effects on sexual reactivity. The same argument could be made with respect to the differences in marijuana’s effect on appetite.17

In 2011, approximately 456,000 drug-related emer- gency department (ED) visits in the DAWN statistics (see Chapter 2) involved marijuana, making it the sec- ond highest category, behind cocaine. In one fourth of these cases, marijuana was the only drug present in the patient’s system at the time. Marijuana-related emer- gency department incidents had increased by about 21 percent from 2009 and about 62 percent from 2004. most likely due to the higher THC concentrations in marijuana and greater numbers of marijuana smokers.18

Acute Psychological and Behavioral Effects In Chapter 5, it was noted that a first-time heroin abuser frequently finds the experience more aversive than plea- surable. With marijuana, it is common for a first-time smoker to feel no discernible effects at all. It takes some practice to be able to inhale deeply and keep the smoke in the lungs long enough (up to forty seconds) for a minimal level of THC to take effect, particularly when smoking low-quality marijuana. Novices often have to be “instructed” to focus on some aspect of the intoxicated

174 ■ Part Two Legally Restricted Drugs in Our Society

state to start to feel intoxicated, but the psychological reactions, once they do occur, are fairly predictable.

The marijuana high, as the name implies, is a feeling of euphoria and well-being. Marijuana smokers typically report an increased awareness of their surroundings, as well as a sharpened sense of sight and sound. They often feel that everything is suddenly very funny, and even the most innocent comments or events can set off uproarious laugh- ter. Usually mundane ideas can seem filled with profound implications, and the individual may believe that her or his creativity has been increased. As with LSD, however, no objective evidence shows that creativity is enhanced by marijuana. Commonly, time seems to pass more slowly while a person is under the influence of marijuana, and events appear to be elongated in duration. Finally, mari- juana smokers frequently report that they feel sleepy and sometimes dreamy. Relatively low THC concentrations in a marijuana joint are not sufficient to be particularly sleep-inducing, though stronger cannabis preparations with higher THC can have strong sleep-inducing effects, particularly when combined with alcohol.19

At the same time, marijuana produces significant def- icits in behavior. The major deficit is a decline in the abil- ity to carry out tasks that involve attention and memory. Speech becomes increasingly fragmented and disjointed; individuals often forget what they, or others, have just said. The problem is that marijuana typically causes such a rush of distracting ideas to come to mind that it is difficult to concentrate on new information coming in. By virtue of a diminished focus of concentration, the performance of both short-term and long-term memory tasks is impaired. In general, these difficulties increase in magnitude as a direct function of the level of THC in the marijuana.20

Not surprisingly, complex motor tasks such as driv- ing a car are more poorly performed while a person is under the influence of marijuana. It is not necessarily a matter of reaction time; studies of marijuana smokers in automobile simulators indicate that they are as quick to respond as control subjects. The problem arises from a difficulty in attending to peripheral information and making an appropriate response while driving.21 One researcher has put it this way:

Marijuana-intoxicated drivers might be able to stop a car as fast as they normally could, but they may not be as quick to notice things that they should stop for. This is probably because they are attending to internal events rather than what is happening on the road.22

Given these observations in the laboratory and on the road, marijuana use is a significant risk factor for an automobile accident. Surveys that have examined ac- cident rates among drivers testing positive for THC in

their bloodstreams have shown them to be about three to seven times more likely to be involved in an accident than drivers testing negative for THC or alcohol.23

An additional problem is that the decline in sen- sorimotor performance can persist well past the point at which the marijuana smoker no longer feels high, particularly in cases of chronic heavy marijuana use. Significant impairments in attention and memory tasks have been demonstrated among heavy marijuana users (daily smokers) twenty-four hours after they last used the drug. Therefore, the possibility exists that some impor- tant aspects of behavior can be impaired following mari- juana smoking, even when an individual is not aware of it. This effect is likely to be result of the very slow rate at which marijuana is eliminated from the body.24

Acute psychological reactions such as paranoia and increased anxiety can occur with marijuana use. However, more severe schizophrenia-like symptoms such as delusions, hallucinations, depersonalization, confusion, and disorientation are far less frequently observed (see Drugs . . . in Focus). If these symptoms

Quick Concept Check 7.1

Understanding the Effects of Marijuana Check your understanding of the effects of marijuana by checking off the response (on the right) that you think is appropriate to each circumstance related to marijuana or other cannabis products (on the left).

circumstance

increases the effect

decreases the effect

1. The resin content in the cannabis is low.

__________

__________

2. You have decided to inhale more deeply.

__________

__________

3. You are smoking hashish instead of marijuana.

__________

__________

4. This is the first time you have ever smoked marijuana.

__________

__________

5. The THC concentration level is relatively high.

__________

__________

Answers: 1. decreases the effect 2. increases the effect 3. increases the effect 4. decreases the effect 5. increases the effect

Chapter 7 Marijuana ■ 175

do occur, they are generally short-lasting and more likely to occur among individuals with preexisting personality disorders. Reports of a substantially higher incidence of psychiatric problems arising from THC exposure in India and North Africa indicate that there is a significant “dose-dependent” effect in the associa- tion between emotional problems and cannabis use in its various forms.25

Effects of Marijuana on the Brain

When THC was isolated in 1964 as the primary agent for the intoxicating properties of marijuana, the next step was to find out specifically how THC affected the brain to produce these effects. In 1990, the mechanism was discovered. Just as with morphine, special receptors in the brain are stimulated specifically by THC. They are concentrated in areas of the brain that are impor- tant for short-term memory and motor control. Unlike

morphine-sensitive receptors, however, THC-sensitive receptors are not found in the lower portions of the brain that control breathing. As a result, no matter how high the THC concentration in the brain, there is no danger of accidental death by asphyxiation.

Once we have identified a specific receptor for a drug, the question inevitably becomes, “Why is it there?” As noted in Chapter 5, when the morphine- sensitive receptor was discovered, it made sense to speculate about a natural morphine-like (opioid) sub- stance that would fit into that receptor. The same spec- ulation surrounded the discovery of the THC-sensitive receptor until 1992, when researchers isolated a natu- ral substance, dubbed anandamide, that activates this receptor and appears to produce the same effects as THC in the brain.

anandamide (a-NAN-duh-mide): A naturally occur- ring chemical in the brain that fits into THC-sensitive receptor sites, producing many of the same effects as marijuana.

Drugs . . . in Focus

The Neurochemical “Yin and Yang” of Cannabis Considering the large number of cannabinoids in the cannabis plant, it should not be surprising that indi- vidually they might have different neurochemical and behavioral effects. Recent studies indicate that two of the cannabinoids have diametrically opposite effects. The first and best known cannabinoid, THC, is the principal psychoactive component, resulting in the marijuana high. It is also considered to be associated with acute symptoms of paranoia and increased anxiety, as well as occasional schizophrenia-like reactions, although these reactions tend to occur only when THC-concentrations are high. On the other hand, cannabidiol (CBD) is associated with opposite effects, producing a reduction in anxiety and fewer instances of severe emotional problems. In effect, CBD can be understood as having a “neuroprotective” effect, making it less likely that adverse emotional reac- tions will occur. Because of the opposing properties of these cannabinoids, different strains of marijuana may

have various psychological effects, depending upon the ratio of THC and CBD.

A 2008 study analyzed hair samples of individuals in three groups: nonusers of cannabis, users testing positive for both CBD and THC, and users testing positive for THC alone. There was a greater incidence of hallucina- tions and delusions in the THC-only group, relative to the other groups, with the THC+CBD group showing no greater incidence than nonusers.

It was not possible in this study to examine the be- haviors of individuals who tested positive for CBD alone, since there are no strains of natural cannabis that have this property. Nonetheless, it is possible that future research will result in the creation of synthetic forms of cannabis containing CBD alone, with the potential for treating individuals suffering from schizophrenia and related disorders (see Chapter 15).

Source: Morgan, C. J., and Curran, H. V. (2008). Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. British Journal of Psychiatry, 192, 306–307.

176 ■ Part Two Legally Restricted Drugs in Our Society

The functions of anandamide and THC-sensitive receptors remain largely a mystery. One study has found that THC stimulates neurons in the nucleus accum- bens in rats, the same area that is affected by a host of other psychoactive drugs, including heroin, cocaine, and nicotine (Chapter 3). The effect, however, is much weaker than with drugs that produce strong signs of dependence. Animals will self-administer marijuana in laboratory studies and, in fact, are able to discriminate high-potency from low-potency marijuana, but their behavior is not as compulsive as that observed with her- oin, cocaine, or nicotine.26

Chronic Effects of Marijuana

Is chronic marijuana smoking harmful over a period of time? What is the extent of tolerance and dependence? Are there long-term consequences for organ systems in the body? Does marijuana lessen one’s potential as a productive human being in society? Does marijuana abuse lead to the abuse of other drugs? These are ques- tions to be considered next.

Tolerance It is frequently reported that experienced marijuana smokers become intoxicated more quickly and to a greater extent than inexperienced smokers when exposed to marijuana joints with equivalent THC concentrations. For many years, this observation sug- gested that repeated administrations of marijuana produced sensitization, or reverse tolerance (a greater sensitivity), rather than tolerance (a lesser sensitivity). If this were true, then we would have been faced with the troubling conclusion that marijuana operates in a way totally opposite to that of any other psychoactive drug considered so far. As it turns out, when animals or humans are studied in the laboratory, marijuana smoking shows tolerance effects that are consistent and clear-cut.

Why, then, is the experience of humans outside the laboratory different from that of animals? One impor- tant factor is the way we measure the quantity of THC consumed. Reaching an effective high from marijuana requires some degree of practice. For example, novice marijuana smokers may not have mastered the breath- ing technique necessary to allow the minimal level of THC to enter the lungs. They may have to smoke a rela- tively large number of marijuana joints initially before they achieve a high. Later, when they have acquired the technique, they may need fewer joints to accomplish

the same effect. In these circumstances, a calculation of the number of joints consumed does not reflect the amount of THC ingested. If you were to control the THC content entering the body, as is done in laboratory studies, you would find the predictable results of toler- ance over repeated administrations.

Another factor that complicates tolerance studies is the slow elimination rate of marijuana. Regular mari- juana smokers are likely to have a residual amount of THC still in the system. This buildup of THC would elevate the total quantity of THC consumed with every joint and induce a quicker high. Once again, the impression of sensitization is false; the enhanced effects result from an accumulation of THC in the body. When dosage levels are controlled, the results indicate a consistent pattern of tolerance rather than sensitization. In general, tolerance effects following repeated adminis- trations of THC are greater as the dosage level of THC increases.27

Withdrawal and Dependence Withdrawal symptoms after discontinuance of mari- juana smoking (that is, evidence of physical depen- dence) are observed in both short-term and long-term marijuana users, even when relatively low levels of THC are ingested. In one study, abstinence from smoking marijuana cigarettes with approximately 2 to 3 percent THC levels or equivalent oral doses of THC, administered four times a day over a four-day period, resulted in feelings of irritability, stomach pain, anxi- ety, and loss of appetite. These symptoms began within forty-eight hours and lasted at least two days.28 Chronic marijuana users who have ingested higher levels of THC show negative physical symptoms that are more severe and long lasting, resembling the withdrawal symptoms associated with the chronic use of tobacco. These symptoms, however, are substantially milder than those associated with the chronic use of heroin (Chapter 5) or alcohol (Chapter 9).29

There is also evidence of marijuana craving, indi- cating a degree of psychological dependence in some marijuana smokers, but it is difficult to measure the extent of these feelings or to determine whether these effects are due to circumstances in which marijuana is used in conjunction with other drugs. As was pointed out earlier, any definitive judgment about the possibil- ity of psychological dependence, or about the extent to which psychological dependence may occur in the average marijuana smoker, must be made on the basis of research studies involving THC concentrations that are typical of currently available marijuana.30

Chapter 7 Marijuana ■ 177

Cardiovascular Effects THC produces significant increases in heart rate, but there is no conclusive evidence of adverse effects in the cardiovascular functioning in young, healthy people. The reason why the emphasis is on a specific age group is that most of the studies looking at possible long-term cardiovascular effects have involved marijuana smok- ers under the age of thirty-five; little or no information has been compiled about older populations. For those people with preexisting disorders such as heart disease, high blood pressure, or arteriosclerosis (hardening of the arteries), it is known that the acute effects of mari- juana on heart rate and blood pressure can worsen their condition.

Respiratory Effects and the Risk of Cancer The technique of marijuana smoking involves the deep and maintained inhalation into the lungs of unfiltered smoke on a repetitive basis—probably the worst possible scenario for incurring chronic pulmo- nary problems. In addition, a marijuana joint (when compared with a tobacco cigarette) typically contains about the same levels of tars, 50 percent more hydro- carbons, and an unknown amount of possible con- taminants (Table 7.1). Joints are often smoked more

completely because the smoker tries to waste as little marijuana as possible.

Given all these factors, marijuana smoking pres- ents several risks. One of the immediate consequences affects the process of breathing. When marijuana is inhaled initially, the passageways for air entering and leaving the lungs widen, but after chronic exposure, an opposite reaction occurs. As a result, symptoms of asthma and other breathing difficulties are increased. Overall, even though the effects of a single inhalation of marijuana smoke present greater problems than a single inhalation of tobacco smoke, we need to remember that the patterns of consumption are far from comparable. All things considered, one joint is roughly equivalent to five cigarettes in terms of the amount of carbon monox- ide intake and to four cigarettes in terms of tar intake. The use of a water pipe reduces the harm somewhat, but the risks are still present.

In the respiratory tracts of heavy marijuana smok- ers, molecular abnormalities have been identified that resemble the changes in the respiratory tracts of ciga- rette smokers. The effect of a single marijuana joint is equivalent to that of up to five tobacco cigarettes in this regard. However, marijuana smoking does not increase the risk of developing emphysema, a chronic lung dis- ease associated with tobacco smoking (see Chapter 10). A recent study has indicated occasional and low cumu- lative marijuana use, even over a period of more than twenty years (1985–2006), does not produce adverse effects on lung capacity as indicated by standard pulmo- nary breathing tests.

Does smoking marijuana produce a higher inci- dence of cancer? Given the number of known car- cinogens in marijuana smoke, the potential for an increased risk of cancer exists. However, there is no definitive evidence of increases in lung cancer rates among marijuana smokers, after controlling for tobacco use. But it may still be too soon to answer the question of increased risk of cancer in general. Mari- juana smokers who were twenty years old in the late 1960s have only recently reached the peak ages when cancers appear, and they smoked marijuana contain- ing relatively low THC concentrations at the time. Those individuals more recently exposed to higher- potency marijuana, such as those whose marijuana experience began in the late 1990s, are substantially younger, and it will be decades before they reach an age at which the incidence of cancer becomes a signif- icant concern. Fortunately, there is the possibility, as is the case with cigarette smoking (see Chapter 10), that the risk of cancer declines after a person stops smoking marijuana.31

TABLE 7.1

A comparison of the components of marijuana and tobacco smoke

CoMpoNENT MArIjuANA ToBACCo Carbon monoxide (mg) 17.6 20.2

Carbon dioxide (mg) 57.3 65.0

Ammonia (micrograms) 228.0 178.0

Acetaldehyde (micrograms) 1,200.0 980.0

Acetone (micrograms)* 443.0 578.0

Benzene (micrograms)* 76.0 67.0

Toluene (micrograms)* 112.0 108.0

THC (tetrahydrocannabinol) (micrograms)

820.0 —

Nicotine (micrograms) — 2,850.0

Naphthalene (nanograms) 3,000.0 1,200.0

*See Chapter 13 for information about the health risks of inhaling some of these chemicals.

Source: Julien, R. M. (2001). A primer of drug action (9th ed.). New York: Worth, p. 317.

178 ■ Part Two Legally Restricted Drugs in Our Society

Effects on the Immune System It has been demonstrated that THC has a suppressant effect on the immune system, resulting in a reduction in the body’s defense reactions to infection and disease. Whether or not this effect results in an increased risk among chronic marijuana smokers of acquiring infec- tious diseases or other disorders related to a deficient immune system, however, remains unclear. Long-term epidemiological studies, in which marijuana-exposed and control populations are compared with regard to the frequency of various diseases, have not been con- ducted on a large-scale basis.32

Effects on Sexual Functioning and Reproduction The reproductive systems of both men and women are adversely affected by marijuana smoking. In men, mari- juana reduces the level of testosterone, reduces sperm count in the semen, and increases the percentage of abnormally formed sperm. In women, marijuana use results in a reduction in the level of luteinizing hormone (LH), a hormone necessary for the fertilized egg to be implanted in the uterus. As little as one marijuana joint, smoked immediately following ovulation, is evidently sufficient for this LH suppression to occur. Despite these hormonal changes in both males and females, however, little or no effect on fertility has been observed.33

The research is sparse on the question, but smok- ing marijuana during pregnancy does not appear to increase the incidence of birth defects. Studies indicate, however, a lower birth weight and shorter length among newborns, as well as a reduction in the mother’s milk. It may be unfair to associate these effects specifically with marijuana smoking, because other drugs (includ- ing alcohol and nicotine) are often consumed during the same period. Even so, the best advice remains that women should avoid marijuana during pregnancy.34

Long-Term Cognitive Effects and the Amotivational Syndrome In 1968, William McGlothlin, a psychologist, and Louis West, a psychiatrist, proposed that chronic mari- juana smoking among young people was responsible for a generalized sense of apathy in their lives and an indifference to any long-term plans or conventional

goals. These changes were called the amotivational syndrome. In their words,

Regular marijuana use may contribute to the devel- opment of more passive, inward-turning personality characteristics. For numerous middle-class students, the subtly progressive change from conforming, achievement-oriented behavior to a state of relaxed and careless drifting has followed their use of signifi- cant amounts of marijuana. . . . Such individuals exhibit greater introversion, become totally involved with the present at the expense of future goals, and demonstrate a strong tendency toward regressive, childlike magical thinking.35

Essentially, McGothlin and West—and probably a sizable proportion of the American public in the late 1960s—were saying, “These people don’t seem to care anymore about things that we think are important, and marijuana’s to blame for it!”

The credibility of the amotivational syndrome theory revolves around two basic questions that need to be examined separately. The first question deals with whether such a syndrome exists in the first place, and the second deals with whether chronic abuse of marijuana is a causal factor. As to the existence of the syndrome, the evidence does suggest that students who smoke mari- juana are at a disadvantage academically. Studies of high school students indicate that those who smoke marijuana on a regular basis (weekly or more frequently) earn lower grades in school (Figure 7.1), are less likely to continue

amotivational syndrome: A state of listlessness and personality change involving a generalized apathy and indifference to long-range plans.

Past month marijuana use

0 5 10 15 20 25

3.1%

6.4%

10.0%

17.9%

A Average B Average C Average D Average or lower

F I G u r E 7 . 1

Percentages of past month marijuana and blunt use among students aged twelve to seventeen and semester grade average.

Note: Blunts are hollowed-out cigars refilled with marijuana.

Source: Substance Abuse and Mental Health Services Administration (2007). Use of marijuana and blunts among adolescents: 2005. The NSDUH Report, p. 3.

Chapter 7 Marijuana ■ 179

on to college, are more likely to drop out, and miss more classes than those who do not smoke it.36 In a survey of high school students graduating in the early 1980s, those who smoked marijuana on a daily basis reported several problems in their lives that are related to motivation: a loss of energy (43 percent), negative effects on relation- ships (39 percent), interference with work and the ability to think clearly (37 percent), less interest in other activi- ties (37 percent), and inferior performance in school or on the job (34 percent).37 It is likely that these percent- ages would be roughly the same today.

These changes are genuine, but we cannot easily establish a direct causal link between marijuana and such global problems, other than to acknowledge that the pres- ence of THC in a student’s system during school hours would be reflected in relatively low levels of overall aca- demic performance. More broadly speaking, we cannot exclude the possibility that marijuana smoking may be, in the words of one expert in the field, “just one behavior in a constellation of related problem behaviors and personality and familial factors” that hamper an adolescent’s ability to do well in school and in life. Lifestyle decisions based upon unconventionality, nontraditionality, or nonconfor- mity are frequently observed among marijuana users.38

We also cannot exclude the possibility that involve- ment with marijuana may closely correlate with involve- ment in a deviant subculture—a group of friends and associates who feel alienated from traditional values such as school achievement and an aspiration toward a promising future (see Chapter 1). Either of these fac- tors, in combination with the regular ingestion of mari- juana, could account for the motivational changes that are observed. The point is that we cannot conclude that such life-style changes are purely pharmacological.

It is clear that acute marijuana intoxication produces significant cognitive deficits, as evidenced by reduced scores on tasks of attentiveness and memory, but the question remains whether these problems are increased, or perhaps may even become irreversible, as a result of long-term marijuana use. Large and well-controlled stud- ies have shown that cognitive deficits in heavy marijuana smokers, relative to nonusers, are observed after twelve to seventy-two hours of abstinence. In other words, the specific signs of cognitive impairment among long-term marijuana smokers may linger for as long as three days after active marijuana smoking. In one study, however, testing of subjects after twenty-eight days of abstinence revealed equivalent performance scores between non- users and heavy users of marijuana, even though the latter group had smoked marijuana several thousands of times over a period ranging from ten to thirty-three years. No correlation was seen between the test scores

after twenty-eight days of abstinence and the number of episodes of marijuana use over an individual’s lifetime. Therefore, it appears that behavioral problems related to attention and memory among heavy marijuana smokers can be reversed by stopping marijuana use.39

On the other hand, recent studies indicate that spe- cific brain abnormalities associated with long-term heavy marijuana use have a negative impact on successful information-processing abilities. Specifically, long-term studies of marijuana use from adolescence to adulthood show brain deficits that result in an increased difficulty in inhibiting impulsive behaviors. These neuroanatomi- cal changes may not be reversible, and are more pro- nounced when the age of onset of marijuana use is early (prior to age 16) than when it is later (age 16 or older).40

The Gateway Hypothesis

A widely publicized theory about marijuana smoking concerns the possibility of a relationship between mari- juana use and the subsequent abuse of illicit drugs such as amphetamines, cocaine, or heroin. The contention that marijuana leads to a greater incidence of drug abuse in general is referred to as the gateway hypothesis. Just as in our consideration of the amotivational syndrome, the evi- dence for this hypothesis must be studied very carefully.

With respect to the gateway hypothesis, we should address three separate issues: (1) whether a fixed sequential relationship exists between the initiation of marijuana use and other forms of drug-taking behavior, (2) whether marijuana use represents a significant risk fac- tor for future drug-taking behavior, specifically increasing the likelihood of using other illicit drugs, and (3) whether marijuana actually causes the use of other illicit drugs.

The Sequencing Question One of the best-replicated findings in the long-term study of drug use is a developmental sequence of involve- ment (stages of progression) in drug-taking behavior. In the United States as well as other Western societies, use of alcohol and cigarettes precedes marijuana use, and marijuana use precedes use of other illicit drugs. As pub- lic health researcher Denise Kandel has expressed it,

Very few individuals who have tried cocaine and her- oin have not already used marijuana; the majority have previously used alcohol or tobacco.41

gateway hypothesis: The idea that the abuse of a specific drug will inherently lead to the abuse of other, more harmful drugs.

180 ■ Part Two Legally Restricted Drugs in Our Society

Nonetheless, it is important to point out that an over- whelming proportion of young marijuana smokers do not go on to use other illicit drugs. As expressed in a 1999 newspaper editorial on this point, “millions of baby boomers . . . once did, indeed, inhale. They later went into business, not cocaine or heroin.”42

The Association Question From a statistical perspective, the association between marijuana use and subsequent use of other illicit drugs is not controversial. Generally speaking, marijuana smokers are several times more likely to consume illicit drugs such as cocaine and heroin during their lifetimes than are people who never smoked marijuana. The greater the frequency of marijuana smoking and the earlier an individual first engages in marijuana smok- ing, the greater the likelihood of his or her becoming involved with other illicit drugs in the future.

A precise determination of the magnitude of risk involved in marijuana use requires studies that take into account a range of genetic and environmental vari- ables that might act as risk factors or protective factors for drug-taking behavior (see Chapter 1). A 2003 study set out to control for these variables by investigating a specific subpopulation of twins; one member of each twin pair reported marijuana use by the age of seven- teen, and the other reported no marijuana use at all. Examining twins enabled the researchers to calculate the increased risk of future drug-taking behavior when environmental factors (in the case of fraternal twins) and both environmental and genetic factors (in the case of identical twins) were controlled. Results showed that early marijuana users were about two and one-half times more likely to use heroin later in life, four times more likely to use cocaine or other stimulants, and five times more likely to use hallucinogens. In general, they were twice as likely to become alcoholic and twice as likely to develop any form of illicit drug abuse or dependence.

The question of whether future twin studies using this approach will find the increased risk from mari- juana use to be higher than the increased risk from alco- hol or tobacco use remains unanswered. In any case, the fact that marijuana use is one of the risk factors for illicit drug use in other forms reinforces the need to develop intervention programs for marijuana users that might discourage subsequent drug use, as well as prevention programs for youths to reduce the incidence of mari- juana use in the first place.43

In the final analysis, however, the statistical rela- tionship between marijuana smoking and other forms of drug-taking behavior may simply reflect the sequential

pattern of drug use among multiple-drug (polydrug) users. Essentially, they begin using high-prevalence drugs (such as alcohol, tobacco, and/or marijuana) ear- lier than they begin using low-prevalence drugs (such as cocaine and/or heroin). This effect can be viewed as due not to the drugs themselves but, rather, to the rela- tive differences in prevalence rates. Numerous statistical relationships exist between other types of common and uncommon behaviors in our lives:

For example, most people who ride a motorcycle (a fairly rare activity) have ridden a bicycle (a fairly common activity). Indeed, the prevalence of motor- cycle riding among people who have never ridden a bicycle is probably extremely low. However, bicycle riding does not cause motorcycle riding, and in- creases in the former will not lead automatically to increases in the latter.44

The Causation Question The strongest form of the gateway hypothesis relates to the possibility of a causal link between marijuana smok- ing and the use of other illicit drugs. With respect to the causation issue, Erich Goode, a sociologist and drug- abuse researcher, has distinguished between two schools of thought, which he calls the intrinsic argument and the sociocultural argument.

The intrinsic argument asserts that some inherent property of marijuana exposure itself leads to physi- cal or psychological dependence on other illicit drugs. According to this viewpoint, the pleasurable sensations induced by marijuana create a biological urge to con- sume more potent substances, through a combination of drug tolerance and drug dependence.

In contrast, the sociocultural argument holds that the relationship exists not because of the pharmaco- logical effects of marijuana but because of the activi- ties, friends, and acquaintances that are associated with marijuana smoking. In other words, the sociocultural explanation asserts that those who smoke marijuana tend to have friends who not only smoke marijuana themselves but also abuse other drugs. These friends are likely to have positive attitudes toward substance abuse in general and to provide opportunities for drug experimentation.

Professionals in the drug-abuse field have con- cluded that if any such causal link exists, the result is socioculturally based rather than related to the pharma- cological properties of marijuana itself. The consensus is that any early exposure to psychoactive substances in general, and to illicit drugs such as marijuana in

Chapter 7 Marijuana ■ 181

particular, represents a “deviance-prone pattern of behavior” that will be reflected in a higher incidence of exposure to psychoactive drugs of many types later in life. It is interesting to note that early adolescent marijuana use among males also increases the risk in late adoles- cence of delinquency, having multiple sexual partners, not always using condoms during sex, perceiving drugs as not harmful, and having problems with cigarettes and alcohol. Generally speaking, marijuana smokers show a greater inclination toward risk-taking behavior and are more unconventional with regard to social norms.45

Patterns of Marijuana Smoking

From as early as their days in elementary school, most young Americans have had to come to terms with mari- juana as a pervasive element in their lives. Just as nearly all adolescents have had to decide whether to drink and whether to smoke cigarettes, they also have had to decide whether to smoke or not smoke marijuana.

Marijuana is undoubtedly the dominant illicit drug in U.S. society today, used by 80 percent of current illicit drug users (Figure 7.2). For more than six out of ten illicit drug users, marijuana is the only illicit drug being used. From the National Survey on Drug Use and Health conducted in 2011, it is estimated that an astounding 108 million Americans, about 42 percent of the U.S. population over the age of twelve, have smoked marijuana at least once during their lives. More than 18 million Americans are estimated to have smoked marijuana within the past thirty days. About 48 percent of individuals between 18 and 20 years old in 2011 had smoked marijuana at least once in their lives; about 22 percent had done so in the past month.46

Among high school seniors surveyed in 2011, 36 percent reported having smoked marijuana in the past year, 23 percent reported having done so in the past month, and 7 percent smoked on a daily basis. Among eighth graders, 13 percent reported smoking marijuana in the past year and 7 percent in the past month.47

Quick Concept Check 7.2

Understanding the Adverse Effects of Chronic Marijuana Abuse Check your understanding of the possible adverse ef- fects of either acute or chronic exposure to marijuana by checking off true or false next to each of the following assertions.

assertion true false

1. The immune system will be impaired.

__________

__________

2. The risk of lung cancer will increase.

__________

__________

3. Driving ability will be significantly impaired.

__________

__________

4. Birth defects will be more frequent.

__________

__________

5. It is likely that academic performance will decline when a person smokes marijuana regularly.

__________

__________

6. Marijuana smoking will cause the smoker to experiment with cocaine or heroin in the future.

__________

__________

7. Marijuana smoking in adolescence will generally be preceded by experimen- tation with tobacco or alcohol

__________

__________

Answers: 1. true 2. false 3. true 4. false 5. true 6. false 7. true Marijuana

only

Some illicit drug other than marijuana

Marijuana and some other illicit drug

20%

16%

64%

F I G u r E 7 . 2

Types of drugs used by illicit drug users aged twelve or older in the past month in 2011.

Source: Substance Abuse and Mental Health Services Admin- istration (2012). Results from the 2011 National Survey on Drug Use and Health: National findings. Rockville, MD: Substance Abuse and Mental Health Services Administration, p. 13.

182 ■ Part Two Legally Restricted Drugs in Our Society

Causes for Concern

Current prevalence rates among young people are sub- stantially lower than those in the 1970s. Nonetheless, there is some concern that marijuana smoking rates are increasing. In other words, the “roller-coaster ride” of marijuana use monitored over the decades (see Fig- ure 1.3) appears to be entering a new upward phase. In 2009, Lloyd Johnston of the University of Michigan survey cautioned that “a key belief about the degree of risk associated with marijuana use has been in decline among young people . . . and the degree to which teens disapprove of use of the drug has recently begun to decline.”48 In 2011, less than half of high school seniors judged “regular marijuana smoking” as representing “great risk,” whereas seniors in 1992 had judged it as representing “great risk” by a three-to-one margin.49

A second concern with regard to present-day mari- juana use has to do with an increased potency in the cannabis products that are available. As noted earlier,

a typical marijuana joint in the psychedelic era several decades ago contained approximately 1 to 2 percent THC; the average concentration has now risen above 6 percent to as high as 10 percent and, in the case of recent strains of sinsemilla, as high as 15 percent. It is reasonable to assume that the adverse effects of chronic marijuana smoking will be more intense than the rela- tively mild symptoms associated with marijuana use in the past. In addition, there are new synthetic forms of marijuana that can produce serious adverse side-effects (Health Alert). A third concern applies to any illicit street drug: the possibility for adulteration. As empha- sized in earlier chapters, what you think you are buying is not always what you get. Each year brings with it a new group of ingredients, some of them newly intro- duced drugs and others merely inventive creations from already available materials, ready to be combined with marijuana either to weaken its effects or to change the overall psychoactive result by some synergistic or other interactive effect.

H E A L T H A L E r T !

A Synthetic Marijuana called Spice In 2010, the Drug Enforcement Administration was alerted to a new leafy-herb product, marketed under the name “spice” (alternately, “K2”) that began to be available through smoke shops and other small retail outlets. Since spice has been sold officially as a “herbal incense” and therefore as a legal commodity, retailers were able to curt the law prohibiting sale of marijuana itself. In actuality, spice contains a powerful cannabinoid called JWH-018, which can bind with THC receptors at a rate four times greater than THC itself. As a consequence, administra- tion of spice results in a powerful marijuana-like high. Standard drug testing screening for THC metabolites (see Chapter 12) cannot be used for individuals smoking spice, though specialized tests to include detection of JWH-018 are presently being developed. An estimated 11,000 of the 4.9 million drug-related emergency department visits in 2010 were linked to spice.

In 2011, the DEA executed its emergency schedul- ing authority (under the Controlled Substance Act) to include JWH-018 and other similar cannabinoids as Schedule I controlled substances, as they have for THC in natural marijuana. Emergency physicians had reported individuals ingesting spice with serious side effects that

Where to go for assistance: http://www.drugabuse.gov/publications/drugfacts/ spice-synthetic-marijuana

This web site, issued by the National Institute on Drug Abuse, provides up-to-date information on the health effects and patterns of abuse of spice. Prevention and treatment strategies are also provided.

included convulsions, anxiety attacks, elevated heart rate and blood pressure, vomiting, and disorientation.

Recently, most U.S. states and many countries have recently made spice and similar products illegal within their jurisdiction. However, it is likely that spice has moved underground and will become still another option within the illicit drug community.

Sources: Substance Abuse and Mental Health Services Administration (2012, December 4). First-of-its-kind report find that street forms of “synthetic marijuana” products linked to thousands of hospital emergency department visits each year. SAMHSA News Release. Rockville, MD: Substance Abuse and Mental Health Services Administration. U.S. Drug Enforcement Administration (2011, March 1). Chemicals used in “spice” and “K2” type products now under federal control and regulation. DEA Office of Public Affairs, Washington, DC.

Chapter 7 Marijuana ■ 183

Medical Marijuana

Even though the medicinal benefits of marijuana have been noted for thousands of years, strong anti- marijuana sentiment in the United St ates made it difficult until the 1970s to conduct an objective appraisal of its clinical applications. Early research in the effectiveness of marijuana to reduce intraocu- lar (within the eye) pressure and dilate bronchioles in the lungs suggested uses as a possible therapy for glaucoma and asthma, respectively. However, new prescription medications have been shown to be as effective as marijuana in the treatment of these dis- orders. Today, the focus has turned toward the treat- ment of chronic pain, muscle spasticity, nausea, and weight loss.

Muscle Spasticity and Chronic Pain Evidence that marijuana is useful in the treatment of muscle spasticity and lack of mobility associated with neurological diseases such as multiple sclerosis (MS) comes largely from subjective reports. In a randomized placebo-controlled study of MS patients taking oral cap- sules of THC or whole cannabis extract, no significant improvements were observed through objective mea- sures of mobility but about two-thirds of the patients reported that they felt significant relief from muscle spas- ticity and associated chronic pain. In addition, patients frequently report relief from cancer-related pain as well as phantom limb pain (a phenomenon in which pain is experienced as coming from a limb that had been ampu- tated). In many cases, they cite the superiority of smoked marijuana to any other form of treatment (Portrait).50

p o r T r A I T Marcy Dolin—Marijuana Self-Medicator

In a New York Times Magazine article, photographer Steve LaBadessa vividly recalls meeting 71-year-old Marcy Dolin in her Rohnert Park, California, home in 2011. Unlike many people using medical marijuana who were reluc- tant to talk to him—much less allow a photographer to take a picture at such short range—Marcy wasn’t shy at all. But being in such close proxim- ity took its toll on the photographer. There was so much smoke in the room that LaBadessa had to sit in his car for a while afterward to recuperate before driving home.

Dolin had been a marijuana smoker for about 35 years to treat her multiple sclerosis symptoms. Today, she typically smokes eight joints a day and eats a marijuana cookie before bedtime. “It takes the pain and muscle spasms away,” she said. “Without it, I would be living on morphine and other horrible drugs. I couldn’t do that to my family. That’s no life, and I would have ended it. That’s the truth.”

She used to take Neurontin but she couldn’t stop crying, and it put her in a depressed fog. She had been warned

that she might be arrested but she couldn’t care less about that.

The medical marijuana issue as- sumed national importance in the 1990s after California voters in 1996 passed the Compassionate Use Act, legalizing marijuana for medical use within the state, the first U.S. state to have done so. After the Drug Enforce- ment Administration (DEA) seized doctor-prescribed marijuana from the home of a patient, advocates of medical marijuana sued the DEA and then–U.S. Attorney General John Ashcroft in federal district court and won. However, in the 2005 U.S. Su- preme Court case Raich v. Ashcroft, the legal status of medical marijuana within the state of California was overturned in favor of arguments that federal regu- lations prohibiting marijuana use under any circumstances were paramount.

The litigant was Angel McClary Raich who had become permanently disabled in 1995, with multiple diagno- ses that included an inoperable brain tumor, life-threatening wasting syn- drome, chronic pain disorders, seizure disorder, nausea, and scoliosis (a pain- ful back condition). After her physician

recommended cannabis use as a medication for her symptoms, Raich became one of the fourteen “medi- cal necessity” patients at the Oakland Cannabis Buyers’ Cooperative who were represented in the court cases that led up to the Supreme Court decision.

As of 2012, eighteen U.S. states and the District of Columbia have legalized medical marijuana, and two states have legalized its recreational use. In 2009, the federal government issued a “non-interference” policy with respect to medical marijuana use within states that allow it. Nonetheless, the legal challenges and drug enforce- ment conflicts between state’s rights and federal prerogatives regarding marijuana use continue.

Sources: LaBadessa, S. (2011, March 20). Self-medicator, Rohnert Park, Calif. New York Times Magazine, p. 23. Who Is Angel McClary Raich? Angel Wings Patient Outreach, Inc. Web Site, an- geljustice.org. Declaration of Frank Henry Lucido, M.D., In Support of the Plaintiff Angel McClary Raich, October 20, 2002, U.S. District Court for the Northern District of California.

184 ■ Part Two Legally Restricted Drugs in Our Society

Nausea and Weight Loss Chemotherapy in the course of cancer treatment pro- duces an extreme and debilitating nausea, lack of appe- tite, and loss of body weight, symptoms that are clearly counterproductive in helping an individual contend with an ongoing fight against cancer. AIDS patients suf- fer from similar symptoms, as do those diagnosed with the gastrointestinal ailment Crohn’s disease. Under these circumstances, standard antiemetic (antivomit- ing) drugs are frequently ineffective. The beneficial effect of marijuana, specifically THC, as an antiemetic drug when treatment by traditional antiemetic medi- cations have failed, is an important therapeutic application.51

At the same time, the use of marijuana per se as a therapeutic agent has distinct disadvantages. First, the typical administration through smoking presents a sig- nificant health risk to the lungs. Second, because mari- juana is insoluble in water, suspensions in an injectable form cannot be prepared. Since 1985, however, two legal prescription drugs containing THC or a variation of it have been made available in capsule form and clas- sified as Schedule II controlled substances. Dronabinol (brand name: Marinol) is essentially THC in a sesame oil suspension; nabilone (brand name: Cesamet) is a synthetic variation of THC. Both drugs have been shown to be clinically effective against nausea, although the personal reactions of patients taking these drugs vary considerably.52

The Medical Marijuana Controversy Even though Marinol and Cesamet are presently in use, U.S. federal authorities have resisted the reclas- sification of marijuana itself or of any other cannabis product from the Schedule I category of controlled substances (drugs that have no medical application) to the Schedule II category (which includes mor- phine and cocaine). Only a handful of “compassion- ate use” applications have been approved, and the entire program for reviewing new applications was curtailed in 1992.

Despite opposition from federal authorities, advo- cacy for the medical application of marijuana has grown

considerably. Unfortunately, the facts about medical marijuana sometimes have been lost in a thicket of poli- tics and opposing ideologies. A case in point is the inter- pretation of a major report on the possibility of using marijuana as a medical treatment, issued by the Insti- tute of Medicine, a branch of the National Academy of Sciences, in 1999. In its preface, the report began by acknowledging the problems involved:

Although marijuana smoke delivers THC and other cannabinoids to the body, it also delivers harmful substances, including most of those found in tobacco smoke. In addition, plants contain a variable mix- ture of biologically-active compounds and cannot be expected to provide a precisely defined drug effect. For these reasons, this report concludes that the fu- ture of cannabinoid drugs lies not in smoked mari- juana, but in chemically-defined drugs that act on the cannabinoid systems that are a natural compo- nent of human physiology.53

In focusing on the report’s preface, the federal Office of National Drug Control Strategy has emphasized the potential health risks of marijuana smoking and the im- precision of its administration as a justification for the continued prohibition of marijuana for medical pur- poses. Largely ignored has been one of the report’s main conclusions within the report itself.

Until a nonsmoked, rapid-onset cannabinoid drug delivery system becomes available, we acknowledge that there is no clear alternative for people suffering from chronic conditions that might be relieved by smoking marijuana, such as pain or AIDS wasting.54

In effect, the report concluded that, although smoked marijuana could not be recommended for long-term use, short-term use appeared to be suitable for treating specific conditions when patients failed to respond well to traditional medications.

As of 2012, eighteen U.S. st ates (Alaska, Ari- zona, California, Colorado, Connecticut, Delaware, Hawaii, Maine, Massachusetts, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont, and Washington) and the District of Columbia have authorized marijuana smoking for the relief of pain and discomfort or the control of nausea and weight loss, when prescribed by a physician. In New Jersey, tight restrictions on medical marijuana have been established: Patients must suffer from spe- cific diseases such as cancer and glaucoma and must demonstrate severe or chronic pain, nausea, seizures, muscle spasms, or wasting syndrome (loss of weight or body mass).

dronabinol (droh-NAB-ih-nol): A prescription drug containing delta-9-tetrahydrocannabinol (THC). Brand name is Marinol.

nabilone (NAB-ih-lone): A prescription drug con- taining a synthetic variation of delta-9-tetrahydro- cannabinol (THC). Brand name is Cesamet.

Chapter 7 Marijuana ■ 185

In addition, two U.S. states approved in 2012 the legalization of recreational marijuana use, with specific regulatory safeguards. In Colorado, adults over 21 can grow up to six marijuana plants in a private secure area and possess up to an ounce of marijuana, although pub- lic use is banned. In Washington, adults over 21 can buy and possess up to an ounce of marijuana from a state-licensed system of marijuana growers, processors, and stores. Standardized testing procedures for driving under the influence will be implemented.55

How would the contradictory positions in the stat- utes of states and the federal government regarding medical marijuana be reconciled? In a significant rever- sal of federal enforcement policy, the U.S. Department of Justice announced in 2009 that

It will not be a priority to use federal resources to prosecute patients with serious illnesses or their care- givers who are complying with state laws on medical marijuana, but we will not tolerate drug traffickers who hide behind claims of compliance with state law to mask activities that are clearly illegal.55

In effect, the Department of Justice has returned the question of medical marijuana to the jurisdic- tion of the states without altering its official stance on a federal level that marijuana is a controlled substance without medical use. At the same time, it has signaled the requirement that the states set up regulations that limit marijuana use to legitimate medical circum- stances. Recently, U.S. states with medical marijuana laws have had to contend with federal drug enforce- ment campaigns, when the lines have blurred between legal and illegal marijuana use. How the federal govern- ment will handle the newly established legalization of marijuana in Colorado and Washington remains to be seen.56 Meanwhile, public opinion in favor of medi- cal marijuana in general has increased steadily over the years, judging from the more than one-third of U.S. states authorizing the practice. In a national CBS News poll conducted in 2011, 77 percent of American adults favored legalizing the possession of small amounts of marijuana for medicinal purposes.57

Canada has officially approved the medicinal use of marijuana since 2001. It is legal for Canadian patients to grow and smoke marijuana if their symptoms have been certified by a physician as warranting this treatment. It is also permitted, under these circumstances, to request marijuana, free of charge, from government-operated cannabis farms in Manitoba. In 2005, the FDA-equiva- lent agency in Canada approved the prescription use of Sativex, a liquid spray derived from the cannabis plant. In 2006, the FDA approved clinical testing of Sativex

for potential sale in the United States. By providing a nonsmoking means of administration, this formulation circumvents arguments that medical marijuana smok- ing presents increased risks of smoking-related diseases (see Chapter 10).58

The Issues of Decriminalization and Legalization

What, then, should public policy be toward marijuana smoking in the United States today? To deal with this question, we need first to review how public policy with respect to marijuana regulation has evolved since the 1970s. As described earlier, the dramatic emergence dur- ing the 1960s of marijuana as a major psychoactive drug initiated a slow but steady reassessment of myths that had been attached to it for decades. By 1972, the American Medical Association and the American Bar Association had proposed a liberalization of laws regarding the posses- sion of marijuana. In 1972, the National Commission on

A DEA officer supervises the confiscation of a small-scale marijuana crop.

186 ■ Part Two Legally Restricted Drugs in Our Society

Marijuana and Drug Abuse, authorized by the Compre- hensive Drug Abuse Prevention and Control Act of 1970, encouraged state legislators around the country to con- sider changes in their particular regulatory statutes related to marijuana.59 Since that time, several states, including California, Oregon, Colorado, Minnesota, and North Carolina, have adopted some form of decriminalization laws with respect to the possession of marijuana in small amounts (usually less than an ounce or so). Essentially, decriminalization has meant that possession under these circumstances is considered a civil (noncriminal) offense, punishable by a fine rather than imprisonment.

You may find it surprising or not surprising (depend- ing on your personal views) that official decriminalization has not been demonstrated to result in an upturn in the incidence of marijuana smoking. Statistics drawn from states that either have or have not decriminalized show little or no difference.60 In addition, attitude surveys con- ducted in California before and after the enactment of

such statutes indicate that the acceptance of marijuana among college students actually declined following decriminalization.61

Marijuana legalization is different from decriminal- ization in that it allows anyone over the age of 21 to pur- chase marijuana for his or her own use, typically with regulations similar to the use of alcohol. As with recent voter referendum results regarding medical marijuana, public support for marijuana legalization tends to be mixed. In 2010, a California state referendum to legal- ize marijuana was defeated by a 54 to 46 percent vote. In 2012 elections, Colorado and Washington voters approved legalized marijuana use by adults, but Oregon voters rejected it. Nonetheless, support for such a policy is steadily growing. From the late 1970s to the mid- 1990s, acceptance of marijuana legalization had never exceeded 25 percent. According to a 2013 Pew Research Center national poll, 52 percent of Americans now favor legalizing marijuana, while 45 percent are opposed, marking the first time that those in favor have gained the majority. Legalization is favored by 70 percent of those who have ever tried marijuana and 89 percent of those who have tried it in the past year.62

Summary

A Matter of Terminology ● Marijuana is one of several products of Cannabis sa-

tiva, or the common hemp plant, grown abundantly throughout the world.

● Various cannabis products are distinguished in terms of the content of cannabis resin and, in turn, the con- centration of THC, the active psychoactive agent.

The History of Marijuana and Hashish ● The earliest records of marijuana come from Chi-

nese writings nearly five thousand years ago; the use of hashish originated in North Africa and Persia in the ninth or tenth century A.D.

● In the United States, marijuana was available in pat- ent medicines during the late 1800s, but its popularity did not become extensive until the 1920s.

● Federal and state regulation of marijuana began in the 1930s; penalties for possessing and selling mari- juana escalated during the 1940s and 1950s.

● The emergence of marijuana on American college campuses and among American youth in general dur- ing the late 1960s, however, forced a reexamination of public policy regarding this drug, leading to a more lenient approach in the 1970s.

Acute Effects of Marijuana ● Because marijuana is almost always consumed

through smoking, the acute effects are rapid, but be- cause it is absorbed into fatty tissue, its elimination is slow. It may require days or weeks (in the case of ex- tensive exposure to marijuana) for THC to leave the body completely.

● Acute physiological effects include cardiac accelera- tion and a reddening of the eyes. Acute psychological effects, with typical dosages, include euphoria, giddi- ness, a perception of time elongation, and increased hunger. There are impairments in attention and memory, which interfere with complex visual–motor skills such as driving an automobile.

● The acute effects of marijuana are now known to be due to the binding of THC at special receptors in the brain.

Chronic Effects of Marijuana ● Chronic marijuana use produces tolerance effects;

there is no physical dependence when doses are mod- erate, and only a mild psychological dependence.

● Carcinogenic effects are suspected because mari- juana smoke contains many of the same harmful

decriminalization: The policy of making the posses- sion of small amounts of a drug subject to a small fine but not criminal prosecution.

Chapter 7 Marijuana ■ 187

components that tobacco smoke does, and in the case of marijuana smoking, inhalation is deeper and more prolonged.

The Amotivational Syndrome and the Gateway Hypothesis ● The idea that there exists an “amotivational syn-

drome,” characterized by general apathy and an in- difference to long-range planning, as a result of the pharmacological effects of chronic marijuana use has been largely discredited. An alternative explanation for the behavioral changes is that chronic marijuana users are involved in a deviant subculture that tends to undermine traditional values of school achievement and long-term aspirations.

● Another idea that has been related to chronic mari- juana use is the gateway hypothesis, which asserts that marijuana inherently sets the stage for future pat- terns of drug abuse. Research studies have indicated that the use of alcohol and cigarettes precedes mari- juana use and that marijuana use precedes the use of other illicit drugs. In addition, marijuana use and the subsequent use of other illicit drugs are statisti- cally correlated. However, there is little evidence that some inherent property of marijuana exposure itself leads to physical or psychological dependence on other drugs.

patterns of Marijuana Smoking ● The current prevalence rate of marijuana smoking

among adolescents and young adults is lower than in

the late 1970s. However, in 2011, 36 percent of high school seniors reported smoking marijuana in the past year.

● Other areas of concern are the considerably greater potency of marijuana that is now available and the continuing potential risk of marijuana adulteration.

Medical Marijuana, Decriminalization, and Legalization ● Marijuana has been useful in the treatment of glau-

coma and asthma, but its most effective application to date has been in the treatment of symptoms of nau- sea and weight loss. As of 2012, eighteen U.S. states had approved medical marijuana. In 2009, a signifi- cant reversal of federal policy on medical marijuana occurred when the U.S. Department of Justice an- nounced that it would not be a national priority to use federal resources to prosecute patients with serious illnesses or their caregivers who are complying with state laws on medical marijuana. However, the federal government is still officially on record as classifying marijuana as a Schedule I controlled substance, indi- cating that it is considered to have no medical use.

● Present public policy in the United States toward marijuana smoking has evolved to the point of es- sentially decriminalizing the possession of marijuana in small amounts. A majority of Americans now support marijuana legalization, and two U.S. states (Coiorado and Washington) have enacted statutes to that effect.

Key Terms

amotivational syndrome, p. 178

anandamide, p. 175 bhang, p. 170 cannabinoids, p. 169

Cannabis sativa, p. 168 decriminalization, p. 186 delta-9-tetrahydrocannabinol

(THC), p. 169 dronabinol, p. 184

gateway hypothesis, p. 179

hashish, p. 169 hashish oil, p. 169 hashish oil crystals, p. 169

joint, p. 172 marijuana, p. 169 nabilone, p. 184 reefer, p. 172 sinsemilla, p. 169

Endnotes

1. Anslinger, H. J.; with Cooper, C. R. (1937, July). Marihuana: Assassin of youth. American Magazine, pp. 18–19, 150-153. Reprinted in Musto, D. F. (2002). Drugs in America: A documentary history. New York: New York University Press, pp. 433-440.

2. Abel, E. L. (1980). Marihuana, the first twelve thousand years. New York: Plenum Press, p. ix.

3. Bloomquist, E. R. (1968). Marijuana. Beverly Hills, CA: Glencoe Press, pp. 4–5.

4. Abel, Marihuana, p. 4. Palfai, T., and Jankiewicz, H. (1991). Drugs and human behavior. Dubuque, IA: W. C. Brown, p. 452.

5. Abel, Marihuana, pp. x–xi. 6. Goode, E. (2012). Drugs in American society (8th ed.).

New York: McGraw-Hill, p. 208. National Drug Intelligence Center (2009). Domestic cannabis cultivation assessment 2009. Washington, DC: U.S. Department of Justice, p. 4. National Drug

188 ■ Part Two Legally Restricted Drugs in Our Society

Intelligence Center (2008). National drug threat assessment: 2009. Washington, DC: U.S. Department of Justice, p. 18. Pulse check: Marijuana report. Washington, DC: White House Office of Drug Control Policy.

7. Abel, Marihuana, p. 12. 8. Bonnie, R. J., and Whitebread, C. H. (1974). The marihuana

conviction: A history of marihuana prohibition in the United States. Charlottesville, VA: University Press of Virginia, p. 3.

9. Abel, Marihuana, pp. 218–222. 10. Anslinger, H. J., and Tompkins, W. F. (1953). The traffic in

narcotics. New York: Funk & Wagnalls, pp. 37–38. Cited in Inciardi, J. A. (2002). The war on drugs III. Boston: Allyn and Bacon, p. 46.

11. Lee, M. A., and Shlain, B. (1985). Acid dreams: The com- plete social history of LSD. New York: Grove Weidenfeld.

12. Julien, R. M. (2005). A primer of drug action (10th ed.). New York: Worth, pp. 565–567.

13. Ibid., p. 566. 14. Allen and Hanbury’s athletic drug reference (1992).

Research Triangle Park, NC: Clean Data, p. 33. Wadler, G. I., and Hainline, B. (1989). Drugs and the athlete. Philadelphia: F. A. Davis, pp. 208–209.

15. Grinspoon, L., and Bakalar, J. B. (1997). Marihuana. In J. H. Lowinson, P. Ruiz, R. B. Millman, and J. G. Langrod (Eds.), Substance abuse: A comprehensive textbook (3rd ed.). Baltimore, MD: Williams and Wilkins, pp. 199–206.

16. Jones, R. T. (1980). Human effects: An overview. In R. C. Petersen (Ed.), Marijuana research findings: 1980 (NIDA Research Monograph 31). Rockville, MD: National Institute on Drug Abuse, p. 65.

17. Grilly, D. M. (2006). Drugs and human behavior (5th ed.). Boston: Allyn and Bacon, p. 268.

18. Substance Abuse and Mental Health Services Administration (2013). Drug Abuse Warning Network, National estimates of drug-related emergency department visits 2004–2011. Rockville, MD: Substance Abuse and Mental Health Services Administration, Excel files.

19. Winger, G.; Hofmann, F. G.; and Woods, J. H. (1992). A handbook on drug and alcohol abuse (3rd ed.). New York: Oxford University Press, pp. 123–125.

20. Budney, A. J.; Moore, B. A., and Vandrey, R. (2008). Health consequences of marijuana use. In J. Brick (Ed.), Handbook of the medical consequences of alcohol and drug abuse (2nd ed.). New York: Routledge, pp. 265–272. Hooker, W. D., and Jones, R. T. (1987). Increased susceptibility to memory intrusions and the Stroop in- terference effect during acute marijuana intoxication. Psychopharmacology, 91, 20–24. Ilan, A. B.; Gevins, A.; Coleman, M.; ElSohly, M. A.; and de Wit, H. (2005). Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids. Behavioural Pharmacology, 16, 487–496.

21. Delong, F. L., and Levy, B. I. (1974). A model of atten- tion describing the cognitive effects of marijuana. In

L. L. Miller (Ed.), Marijuana: Effects on human behavior. New York: Academic Press, pp. 103–117. Gieringer, D. H. (1988). Marijuana, driving, and accident safety. Journal of Psychoactive Drugs, 20, 93–101.

22. McKim, W. A., and Hancock, S. D. (2013). Drugs and behavior (7th ed.). Boston: Pearson, p. 323.

23. Ramaekers, J. G.; Berghaus, G.; van Laar, M.; and Drummer, O. H. (2004). Dose related risk of motor vehicle crashes after cannabis use. Drugs and Alcohol Dependence, 73, 109–119.

24. Block, R. I. (1997). Editorial: Does heavy marijuana use impair human cognition and brain function? Journal of the American Medical Association, 275, 560–561. Pope, H. G., Jr., and Yurgelun-Todd, D. (1996). The residual cognitive effects of heavy marijuana use in college stu- dents. Journal of the American Medical Association, 275, 521–527.

25. Budney, Moore, and Vandrey, Handbook, pp. 261–265. Hall, W.; Degenhardt, L.; and Teesson, M. (2004). Can- nabis use and psychotic disorders: An update. Drug and Alcohol Review, 23, 433–443. Julien, A primer of drug action, pp. 568–572. McKim and Hancock, Drugs and behavior, p. 328.

26. Ameri, A. (1999). The effects of cannabinoids on the brain. Progress in Neurobiology, 58, 315–348. Chait, L. D., and Burke, K. A. (1994). Preference for high- versus low-potency marijuana. Pharmacology, Biochemistry, and Behavior, 49, 643–647. Tanda, G.; Pontieri, F. E.; and Di Chiara, G. (1997). Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common μ1 opioid receptor mechanism. Science, 276, 2048–2049. Wickelgren, I. (1997). Research news: Marijuana: Harder than thought? Science, 276, 1967–1968.

27. Abood, M., and Martin, B. (1992). Neurobiology of marijuana abuse. Trends in Pharmacological Sciences, 13, 201–206.

28. Haney, M.; Ward, A. S.; Comer, S. D.; Foltin, R. W. and Fischman, M. W. (1999a). Abstinence symptoms follow- ing oral THC administration in humans. Psychopharma- cology, 141, 385–394. Haney, M.; Ward, A. S.; Comer, S.D.; Foltin, R. W. and Fischman, M. W. (1999b). Absti- nence symptoms following smoked marijuana in humans. Psychopharmacology, 141, 395–404.

29. Budney, A. J.; Hughes, J. R.; Moore, B. A.; and Vandrey, R. (2004). Review of the validity and significance of cannabis withdrawal syndrome. American Journal of Psychiatry, 161, 1967–1977.

30. Duffy, A., and Milin, R. (1996). Case study: Withdrawal syndrome in adolescent chronic cannabis users. Journal of the American Academy of Child and Adolescent Psy- chiatry, 35, 1618–1621. Julien, R. M. (2001). A primer of drug action (9th ed.). New York: Worth, pp. 320–322.

31. Mehra, R.; Moore, B. A.; Crothers, K.; Tetrault, J.; and Fiellin, D. A. (2006). The association between marijuana smoking and lung cancer: A systematic review. Archives of Internal Medicine, 166, 1359–1367. Pletcher, M. J.;

Chapter 7 Marijuana ■ 189

Vittinghoff, E.; Kalhan, R.; Richman, J.; Safford, M., et al. (2012). Association between marijuana exposure and pulmonary function over 20 years. Journal of the American Medical Association, 307, 173–181. Schuckit, M. (2006). Drug and alcohol abuse: A clinical guide to diagnosis and treatment (6th ed.) New York: Springer, pp. 197–205.

32. Committee on Substance Abuse, American Academy of Pediatrics (1999). Marijuana: A continuing concern for pediatricians. Pediatrics, 104, 982–985. Friedman, H.; Newton C.; and Klein, T. W. (2003). Microbial infec- tions, immunomodulation, and drugs of abuse. Clinical Biochemistry Reviews, 16, 209–219.

33. Brands, B.; Sproule, B.; and Marshman, J. (Eds.) (1998). Drugs and drug abuse: A reference text (3rd ed.). Toronto: Addiction Research Foundation. Budney, Moore, and Vandrey, Handbook, p. 258. Committee on Substance Abuse, Marijuana. Grinspoon and Bakalar, Marihuana, pp. 203–204. Male infertility: Sperm from marijuana smokers move too fast, too early (2003, November 3). Health and Medicine Week, pp. 459–460.

34. Grinspoon and Bakalar, Marihuana, p. 203. 35. McGothlin, W. H., and West, L. J. (1968). The marijuana

problem: An overview. American Journal of Psychiatry, 125, 372.

36. Goode, E. (1999). Drugs in American society (5th ed.). New York: McGraw-Hill College, pp. 232–233.

37. Brook, J. S.; Adams, R. E.; Balka, E. B.; and Johnson, E. (2002). Early adolescent marijuana use: Risks for the transition to young adulthood. Psychological Medicine, 32, 79–91. Goode, E. (2012). Drugs in American society (8th ed.). New York: McGraw-Hill, pp. 219–220. Roebuck, M. C.; French, M. T.; and Dennis, M. L. (2004). Adolescent mari- juana use and school attendance. Economics of Education Review, 23, 133–141.

38. Goode, E. (2012), Drugs in American society, pp. 219–220. 39. Fried, P. A.; Wilkinson, B.; and Gray, R. (2005). Neuro-

cognitive consequences of marihuana—A comparison with pre-drug performance. Neurotoxicology and Teratol- ogy, 27, 231–239. Pope, H. (2002). Cannabis, cognition, and residual confounding. Journal of the American Medi- cal Association, 287, 1172–1174. Solowij, N.; Stephens, R. S.; Roffman, R. A.; Babor, T.; Kadden, R.; et al. (2002). Cognitive functioning of long-term heavy can- nabis users seeking treatment. Journal of the American Medical Association, 287, 1123–1131.

40. Brook, J. S.; Zhang, C.; and Brook, D. W. (2011). Devel- opmental trajectories of marijuana use from adolescence to adulthood: Personal predictors. Archives of Pediatric and Adolescent Medicine, 165, 55–60i. Gruber, S. A.; Dahlgren, M. K.; Sagar, K. A.; Gonenc, A.; and Killogre, W. D. (2012). Age of onset of marijuana use impacts in- hibitory processing. Neuroscience Letters, 511, 89–94. Yücel, M.; Solowij, N.; Respondek, C.; Whittle, S.; Fornito, A.; et al. (2008). Regional brain abnormalities associated with long-term heavy cannabis use. Archives of General Psychiatry, 65, 694–701.

41. Kandel, D. B. (2003). Does marijuana use cause the use of other drugs? Journal of the American Medical Associa- tion, 289, 482–483. Quotation on p. 482. Kandel, D. B. (Ed.) (2002). Stages and pathways of drug involvement: Examining the gateway hypothesis. Cambridge: Cam- bridge University Press.

42. Cited in Medical marijuana: Editorials debate “gateway” effect (1999, April 12). American Health Line, http:// www.ahl.com.

43. Kandel, Does marijuana use cause the use of other drugs? Lynskey, M. T.; Hath, A. C.; Bucholz, K. K.; Slutske, W. S.; Madden, P. A. F.; et al. (2003). The esca- lation of drug use in early-onset cannabis users vs. co-twin controls. Journal of the American Medical Association, 289, 427–433. Martin, K. R. (2001). Adolescent treatment programs reduce drug abuse, produce other improve- ments. NIDA Notes, 16 (1), 11–12. Martin, K. R. (2001). Television public service announcements decrease mari- juana use in targeted teens. NIDA Notes, 16 (1), 14.

44. Zimmer, L., and Morgan, J. P. (1997). Marijuana myths, marijuana facts: A review of the scientific evidence. New York: Lindesmith Center, p. 37.

45. Goode (2012), Drugs in American society, pp. 220–225. 46. Substance Abuse and Mental Health Services Adminis-

tration (2012). Results from the 2011 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Adminis- tration, Tables 1.1A, 1.1B, and 1.5B.

47. Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2012). Monitoring the Future: National survey results on drug use, 1975–2011. Vol. I: Secondary school students 2011. Ann Arbor, MI: Institute for Social Research, The University of Michigan, Tables 2-2, 2-3, and 2-4.

48. Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2009, December 14). Teen mari- juana use tilts up, while some drugs decline in use. Uni- versity of Michigan News Service, Ann Arbor, p. 1.

49. Johnston, O’Malley, Bachman, and Schulenberg (2012). Monitoring the Future, Table 8-3.

50. Budney, Moore, and Vandrey, Handbook, pp. 278–282. Consroe, P.; Musty, R.; Rein, J.; Tillery, W.; and Pertwee, R. (1997). The perceived effects of smoked cannabis on patients with multiple sclerosis. European Neurology, 38, 44–48. Pertwee, R. (2001). Cannabinoid receptors and pain., Progress in Neurobiology, 63, 165–174. Pertwee, R. (2002). Cannabinoids and multiple sclerosis. Pharmacology and Therapeutics, 95, 165–174. Zajicek, J.; Fox, P.; Sand- ers, H.; Wright, D.; Vickery, J.; et al. (2003). Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomized placebo-controlled trial. Lancet, 362, 1517–1526.

51. Julien, A primer of drug action, pp. 577–579. Vestag, B. (2003). Medical marijuana center opens its doors. Journal of the American Medical Association, 290, 877–879.

190 ■ Part Two Legally Restricted Drugs in Our Society

52. Plasse, T. F.; Gorter, R. W.; Krasnow, S. H.; Lane, M.; Shepard, K. V.; et al. (1991). Recent clinical experience with dronabinol. International conference on cannabis and cannabinoids, Chania, Greece. Pharmacology, Biochemistry, and Behavior, 40, 695–700.

53. Institute of Medicine (1999). Marijuana as medicine: Assessing the science base. Washington, DC: National Academy Press, p. vii.

54. Updated from Inciardi, The war on drugs III, pp. 300–301. Institute of Medicine, Marijuana as medicine, p. 8.

55. Johnson, K. (2012, January 27). Marijuana push in Colorado likens it to alcohol. New York Times, p. A13. Kocieniewski, D. (2010, January 12). New Jersey vote backs marijuana for severely ill. New York Times, pp. A1, A18.

56. Attorney General E. H. Holder Jr. (2009, October 19). Attorney General announces formal medical marijuana guidelines. Washington DC: Office of Public Affairs, U.S. Department of Justice. Eckholm, E. (2011, November 5). California dispensaries moving to block U.S. marijuana crackdown. New York Times, p. A17. Johnson, K. (2009, October 26). States pressed into new role on marijuana. New York Times, pp. A1, A16. Quenqua, D. (2011, May 31). Putting a crimp in the hookah. New York Times, pp. A1, A16. Stout, D., and Moore, S. (2009, October 20). U.S. won’t prosecute

in states that allow medical marijuana. New York Times, pp. A1, A21.

57. AP-CNBC marijuana poll—Complete results and analy- sis. CNBC.com, accessed April 20, 2010. Responses to Question 3.

58. Rock announces medical marijuana regulation and progress report on research and domestic supply (2001, July 4). Health Canada news release.

59. National Commission on Marihuana and Drug Abuse (1972). Marihuana: A signal of misunderstanding. Washington, DC: Government Printing Office, pp. 151–167.

60. Johnston, L. D. (1980, January 16). Marijuana use and the effects of marijuana decriminalization. Unpublished testimony delivered at the hearings on the effects of mari- juana held by the Subcommittee on Criminal Justice, Judiciary Committee, U.S. Senate, Washington, DC, p. 5.

61. Melamede, R. J. (2005). Harm reduction—The cannabis paradox. Harm Reduction Journal, 2, 17. Sommer, R. (1988). Two decades of marijuana attitudes: The more it changes, the more it is the same. Journal of Psychoactive Drugs, 20, 67–70.

62. Majority now supports legalizing marijuana (2013, April 4). News release, Pew Research Center for the People and the Press, Washington, DC.

191

I was invited to address a convention of high school teachers

on the topic of drug abuse. When I arrived at the conven-

tion center to give my talk, I was escorted to a special suite,

where I was encouraged to join the executive committee in

a round of drug taking—the drug was a special high-proof

single-malt whiskey. Later, the irony of the situation had its

full impact. As I stepped to the podium under the influence

of a psychoactive drug (the whiskey), I looked out through

the haze of cigarette smoke at an audience of educators

who had invited me to speak to them because they were

concerned about the unhealthy impact of drugs on their

students. The welcoming applause gradually gave way

to the melodic tinkling of ice cubes in liquor glasses, and

I began. They did not like what I had to say.

—John P. J. Pinel, Biopsychology (2011)

After you have completed this chapter, you should have an understanding of

▶ How alcoholic beverages are produced

▶ Alcohol use through history

▶ The history of alcohol regulation from Prohibition to taxation

▶ Patterns of alcohol consumption

▶ The pharmacology of alcohol

▶ Acute physiological and behavioral effects of alcohol

▶ Alcohol and health benefits

▶ Strategies for responsible alcohol consumption

C h a p t e r

8

Part three

Legal Drugs in Our Society

Alcohol: Social Beverage/Social Drug

192 ■ Part three Legal Drugs in Our Society

Pinel’s experience in this opening vignette sums up the central problem facing American society in its dealings with alcohol use and abuse: the frequent fail- ure to acknowledge that alcohol is indeed a psychoac- tive drug.1 You may have heard someone remark, “He drinks a little too much, but at least he’s not doing drugs.” In the eyes of many people, an alcoholic drink is simply a social beverage. In actuality, it is a social drug.

We can see this problem reflected in a number of ways. College courses that cover drug abuse and its effect on society, perhaps the one you are taking right now, are often entitled “Drugs and Alcohol.” Would you personally have expected to cover the effects of alcohol in a course simply entitled “Drugs” in your college catalog? If you answered no, then alcohol had better stay in the course title.

Historically, the U.S. government has had two separate federal agencies under the National Insti- tutes of Health (NIH), one concerned with alcohol abuse (the National Institute on Alcohol Abuse and Alcoholism, NIAAA) and the other concerned with the abuse of other drugs (the National Institute on Drug Abuse, NIDA), a distinction that unfortunately has rein- forced the notion that alcohol is somehow a substance that stands apart from (or worse, is less serious than) other drugs of potential abuse. A recommendation to consoli- date the two agencies had been made in 2010, with an estimated effective date of 2013. However, in 2012, it was decided that NIAAA and NIDA would remain struc- turally separate but pursue a “functional integration” in future research and educational programs that deal with multiple forms of substance abuse.2

Recognizing the immense impact of alcohol use and alcohol abuse on us individually and on our soci- ety, two chapters are devoted to alcohol-related issues. This chapter considers alcohol specifically as a drug, with a unique history and tradition. The next chapter examines the long-term effects, specifically the prob- lems of chronic alcohol abuse and alcoholism. We begin by considering the nature of alcohol itself.

What Makes an Alcoholic Beverage?

Creating ethyl alcohol, through a process known as fermentation, is a remarkably easy thing to do. Almost every culture in the world, at one time or another, has stumbled on the basic recipe. All you need is organic mate- rial with a sugar content (honey, grapes, berries, molasses, rye, apples, corn, sugar cane, rice, pumpkins, to name some examples) left undisturbed in a warm container for a time, and nature does the work. Microscopic yeast cells, floating through the air, land on this material and liter- ally consume the sugar in it, and for every sugar molecule consumed, two molecules of alcohol and two molecules of carbon dioxide are left behind as waste. The carbon dioxide bubbles out, and what remains is an alcoholic bev- erage, less sweet than the substance that began it all but with a new, noticeable “kick.” Basic fermentation results in a beverage with an alcohol content of between 12 and 16 percent, best exemplified by standard grape wine.

The process of fermenting starchy grains such as bar- ley to produce beer, called brewing, is somewhat more complicated. The barley is first soaked in water until it sprouts, producing an enzyme that is capable of break- ing down the starch into sugar. It is then slowly dried, the sprouts are removed, and the remainder (now called barley malt) is crushed into a powder. The barley malt is combined with water, corn, and rice to form a mixture called a mash. The water activates the enzyme so that the

by the numbers . . .

14 Percentage in 2011 of U.S. college students (one in seven) reporting having 10 or more drinks in a row at least once in the past two weeks.

5 Percentage in 2011 of U.S. college students (one in twenty) reporting 15 or more drinks in a row at least once in the past two weeks.

85 Percentage of instances of alcohol-impaired driving reported in 2010 by persons who also reported binge drinking.

Sources: Centers for Disease Control and Prevention (2011). Alcohol-impaired driving among adults—United States, 2010. Morbidity and Mortality Weekly Report, 60, 1351–1356. Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2012). Monitoring the Future: Na- tional survey results on drug use, 1975–2011. Vol. II: College students and adults ages 19–50, 2011. Ann Arbor, MI: Insti- tute for Social Research, The University of Michigan, p. 260.

ethyl alcohol: The product of fermentation of natural sugars. It is generally referred to simply as alcohol, though several types of nonethyl alcohol exist.

fermentation: The process of converting natural sugars into ethyl alcohol by the action of yeasts.

brewing: The process of producing beer from barley grain.

barley malt: Barley after it has been soaked in water, sprouts have grown, sprouts have been removed, and the mixture has been dried and crushed to a powder.

mash: Fermented barley malt, following liquefaction and combination with yeasts.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 193

starches convert into sugars. The addition of yeast to the mash starts the fermentation process and produces an alco- hol content of approximately 4.5 percent. The dried blos- soms of the hop plant, called hops, are then added to the brew for the characteristic pungent flavoring and aroma.

Relying on fermentation alone gives an alcohol concentration of about 15 to 16 percent at best. (An alcohol content above this level starts to kill the yeast and, in doing so, stops the fermentation process.) To obtain a higher alcoholic content, another process, called distillation, must occur.

Distillation involves heating a container of some fermented mixture until it boils. Because alcohol has a lower boiling temperature than water, the vapor pro- duced has a higher alcohol-to-water ratio than the origi- nal mixture. This alcohol-laden vapor is then drawn off into a special coiled apparatus (often referred to as a still), cooled until it condenses back to a liquid, and poured drop by drop into a second container. This new

liquid, referred to as distilled spirits or simply liquor, has an alcohol content considerably higher than 16 per- cent, generally in the neighborhood of 40 to 50 percent.

It is possible, through further distillations, to achieve an alcohol content of up to 95 percent. At this point, however, the alcohol content of distilled spirits is commonly described not by percentage but rather by the designation “proof.” Any proof is twice the percent- age of alcohol: An 80-proof whiskey contains 40 percent alcohol; a 190-proof vodka contains 95 percent alcohol.

The three basic forms of alcoholic beverages are wine, beer, and distilled spirits. Table 8.1 shows the sources of some well-known examples.

distillation: A process by which fermented liquid is boiled and then cooled, so that the condensed product contains a higher concentration of alcohol than before.

distilled spirits: The liquid product of distillation, also known as liquor.

TAble 8.1

Prominent alcoholic beverages and their sources

beverAge Source

Distilled spirits

Brandy Distilled from grape wine, cherries, or peaches

Liqueur or cordial

Brandy or gin, flavored with blackberry, cherry, chocolate, peppermint, lico- rice, etc. Alcohol content ranges from 20% to 55%

Rum Distilled from the syrup of sugar cane or from molasses

Scotch whiskey Distilled from fermented corn and barley malt

Rye whiskey Distilled from rye and barley malt

Blended whiskey A mixture of two or more types of whiskey

Bourbon whiskey Distilled primarily from fermented corn

Gin Distilled from barley, potato, corn, wheat, or rye, and flavored with juniper berries

Vodka Approximately 95% pure alcohol, distilled from grains or potatoes and diluted by mixing with water

Tequila Distilled from the fermented juice of the maguey plant

Grain neutral spirits

Approximately 95% pure alcohol, used either for medicinal purposes or diluted and mixed in less- concentrated distilled spirits

beverAge Source

Wines

Red table wine Fermented red grapes with skins

White table wine Fermented skinless grapes

Champagne White wine bottled before all of the yeast is gone so that remaining carbon dioxide produces a carbonated effect

Sparkling wine Red wine prepared like champagne or with carbonation added

Fortified wines Wines whose alcohol content is raised, or fortified, to 20% by the addition of brandy—for example, sherry, port, Marsala, and Madeira

Wine-like variations

Hard cider Fermented apples

Sake Fermented rice

beers Types of beer vary, depending on brewing procedures.

Draft beer Contains 3–6% alcohol

Lager beer Contains 3–6% alcohol

Ale Contains 3–6% alcohol

Malt liquor Contains up to 8% alcohol

Source: Table compiled by the author.

194 ■ Part three Legal Drugs in Our Society

Alcohol Use through History

Historians point out that fermented honey, called mead, was probably the original alcoholic beverage, dating from approximately 8000 b.c. Beer, requiring more effort than simple fermentation, came on the scene much later; the Egyptians established the first official brewery about 3700 b.c. At that time, beer was quite different from the watery forms we know today. It more closely resembled a bread than a beverage, and the process of producing beer was closer to baking than to brewing.

Evidence of the development of wine comes from references to its sale in the Code of Hammurabi, King of Babylonia, recorded about 1700 b.c. Wine making itself, however, appears to have begun more than three thousand years before that. Excavations of an ancient village in modern-day Iran have revealed the remains of wine-stained pottery dating back to as early as 5400 b.c.3

The first documented distillation of alcohol was the conversion of wine into brandy during the Middle Ages, at a medical school in Salerno, Italy. With an emphasis on its medicinal applications, the new beverage became known in Latin as aqua vitae (“the water of life”), but people quickly caught on to its inebriating possibilities. Brandy became the primary distilled liquor in Europe until the middle of the seventeenth century. At that time the Dutch perfected the process of distilling liquor and flavoring it with juniper berries. A new alcoholic beverage was born: gin.

The enormous popularity of gin throughout Europe marked a crucial point in the history of the impact of alcohol on European society. Because it was easily produced, cheaper than brandy, and faster-acting than wine, gin became an immediate hit for all levels of society, particularly the poorer classes of people. By the mid-1700s, alcohol abuse was being condemned as a major societal problem, and concerns about drunken- ness had become a public issue.

The consequences of gin consumption was felt in many parts of Europe, but it was in English cities that the gin epidemic became a genuine crisis. By 1750, consumption in England had grown to twenty-two times the level in 1685, and the social devastation was obvi- ous. In London, infant mortality rose during this period, with only one of four baptized babies between 1730 and 1749 surviving to the age of five, despite the fact that mortality rates were falling in the countryside. In one

section of the city, as many as one in every five houses was a gin shop.

Consumption of other distilled spirits introduced during this period, such as rum and whiskey, added to the overall problem, but gin was undoubtedly the prime culprit. The social impact of gin drinking in England during the first half of the eighteenth century illustrates how destructive the introduction of a potent and eas- ily available psychoactive drug into an urban society already suffering from social dislocation and instability can be. The consequences in many ways mirrored the introduction of crack cocaine into the ghettos of the United States during the 1980s (Chapter 4).4

Alcohol in Nineteenth-Century America From its earliest days as a nation to the nineteenth century, alcohol use was a fact of life in America.5 Not surprisingly, therefore, the social focus of American communities was the tavern. Not only did taverns serve as public dispensers of alcoholic beverages, but they also served as centers for local business dealings and town politics. Mail was delivered there; travelers could

aqua vitae (AH-kwa veYe-tee): A brandy, the first distilled liquor in recorded history.

The social chaos of “Gin Lane” in London, as interpreted in this engraving by William Hogarth (1697–1764). Notice the falling baby in the foreground as a symbol of rampant child neglect during this time.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 195

stay the night; elections were held there. As an institu- tion, the tavern was as highly regarded, and as regularly attended as the local church.6

By today’s standards, it is difficult to imagine the extent of alcohol consumption that was going on dur- ing the early decades of American history. In 1830, the average per capita intake was an immoderate five drinks a day, more than three times the level of consump- tion today. It was common to take “whiskey breaks” at 11 a.m. and 4 p.m. each day (except Sunday), much as we take coffee breaks today. As far as types of liquor were concerned, rum was the favorite in New England and along the North Atlantic coast, but elsewhere whiskey was king. George Washington himself went into the whiskey business at Mount Vernon in 1797, eventually establishing the largest whiskey distillery of his time.7

The Rise of the Temperance Movement In the late 1700s, prominent physicians, writers, and sci- entists began to consider the adverse effects of alcohol consumption and tried to formulate some kind of social reform to mitigate them. The goal at that time was to reduce the consumption of distilled spirits (liquor) only. It was a temperate attitude toward drinking (hence the phrase temperance movement) rather than an insis- tence on the total prohibition of alcohol in all forms.

In the United States, where the temperance move- ment was to be stronger than anywhere else, its most influential spokesman was Benjamin Rush, a physician, Revolutionary War hero, and signer of the Declaration of Independence. In his 1785 pamphlet “An Inquiry into the Effects of Ardent Spirits on the Human Mind and Body,” Rush vividly described the range of mental and physical dangers associated with excessive alcohol consumption, focusing on the specific dangers of liquor to the citizens of a new democracy:

Strong liquor is more destructive than the sword. The destruction of war is periodic, whereas alcohol exerts its influence upon human life at all times and in all seasons. . . . A nation corrupted by alcohol can never be free.8

Rush’s efforts did not have a major influence on the drinking habits of American society during his lifetime, but they would serve as an inspiration to political and religious groups around the country who saw alcohol consumption in social and moral terms. In their view, drunkenness led to poverty, a disorderly society, and civil disobedience. In short, it was unpatriotic at best and sub- versive at worst. When we hear the phrase “demon rum,”

we have to recognize that many Americans during the nineteenth century took the phrase quite literally. Liquor was demonized as a direct source of evil in the world.

The temperance point of view toward liquor, like any other form of scapegoating, spread like wildfire. In 1831, the American Temperance Society reported that nearly 2 million Americans had renounced strong liquor and that more than eight hundred local societ- ies had been established. With a characteristic succinct- ness, Abraham Lincoln observed, in an 1842 address before a national temperance organization, that prior to the temperance era, the harm done by alcohol was con- sidered to be a result of the “abuse of a very good thing,” whereas his contemporaries now viewed the harm as coming “from the use of a bad thing.”9 By the 1850s, twelve U.S. states (about one-third of the nation at the time) and two Canadian provinces had introduced legis- lation forbidding the sale of “alcoholic” (distilled) drink.

temperance movement: The social movement in the United States, beginning in the nineteenth century, that advocated the renunciation of alcohol consumption.

Even though this 1874 Currier and Ives engraving shows a temperance crusader in full battle regalia, relatively few temperance activists resorted to physical violence.

196 ■ Part three Legal Drugs in Our Society

Whether or not justified in doing so, temperance groups took credit for a dramatic change that was occur- ring in the levels of alcohol consumption in the United States. From 1830 to 1850, consumption of all types of alcohol plummeted from an annual per capita level of roughly 7 gallons to roughly 2 gallons, approximately today’s consumption level. It is quite possible that this decline encouraged the temperance movement to for- mulate its ultimate goal: a prohibition of alcohol con- sumption in any form.

The Road to National Prohibition A major development in the temperance movement was the formation in 1880 of a women’s organization called the Woman’s Christian Temperance Union (WCTU). Almost from the beginning, its primary target was a highly visible fixture of late-nineteenth-century mascu- line American life: the saloon. These establishments were now vilified as the source of all the troubles alco- hol could bring. It is not difficult to imagine how the saloon would have been seen as a significant threat to American women in general.

Bars appeared to invite family catastrophe. They introduced children to drunkenness and vice and drove husbands to alcoholism; they also caused squandering of wages, wife beating, and child abuse; and, with the patron’s inhibitions lowered through drink, the saloon led many men into the arms of prostitutes (and, not incidentally, contributed to the alarming spread of syphilis).10

No wonder the WCTU hated the saloon, and no saloon in the country was safe from their “pray-in” dem- onstrations, vocal opposition, and in some cases violent interventions. Their influence eventually extended into every aspect of American culture. The WCTU and other anti-alcohol forces, such as the newly formed Anti- Saloon League and National Prohibition Party, were soon electing congressional candidates who pledged to enact national legislation banning alcohol consumption throughout the land.

The Beginning and Ending of a “Noble Experiment” In December 1917, Congress passed a resolution “prohibiting the manufacture, sale, transportation, or importation of intoxicating liquors,” the simple wording that would form the basis for the Eighteenth Amendment to the U.S. Constitution. (Note that it did not specifically forbid purchase or use of alcohol.)

The Volstead Act of 1919 set up the enforcement pro- cedures. By the end of the year, the necessary thirty-six states had ratified the amendment, and Prohibition took effect in January 1920.

Despite its lofty aims, Prohibition was doomed to failure. In the countryside, operators of illegal stills (called “moonshiners” because they worked largely at night) continued their production despite the efforts of an occasional half-hearted raid by Treasury agents (known as “revenooers”). The major cities became cen- ters of open defiance. Liquor, having been smuggled into the country, flowed abundantly as saloons turned into speakeasies and operated in violation of the law.

The early years of Prohibition did, however, show positive effects in the area of public health. Alcohol- related deaths, cirrhosis of the liver, mental disorders, and alcohol-related crime declined in 1920 and 1921, but in a few years, the figures began to creep up again, and the level of criminal activity associated with illegal drinking was clearly intolerable.11 By the end of the decade, it was obvious to the vast majority of Americans that the “noble experiment” (as it was called at the time) was not working.

In 1933 President Franklin D. Roosevelt, hav- ing campaigned on a platform to repeal the Volstead Act, signed the necessary legislation that became the Twenty-first Amendment; ratification was swift. Alco- hol was restored as a legal commodity, and its regula- tion was returned once more to local authorities. Over the years, the states gradually repealed their prohibition laws. Mississippi, in 1966, was the last state to do so.

Present-Day Alcohol Regulation by Taxation One immediate benefit of repealing Prohibition was the return of federal revenue from taxes on alcohol. Indeed, the impact on a struggling national economy hard hit by the Depression had been one of the arguments advanced by the repeal movement. In 1933 alone, excise taxes on alcohol sales brought in $500 million, which was used to finance social welfare programs dur- ing the Depression.

The concept of collecting taxes on the basis of alcohol consumption dates back to the very beginning of the United States as a nation. In 1794, the newly formed U.S. Congress passed a law imposing an excise tax on the sale of whiskey. After a short-lived Whiskey Rebellion in which President Washington had to order federal militia to subdue Appalachian farmers who had refused to pay the new tax, the practice of taxing alcohol was accepted and has continued to the present day as an appropriate way of raising tax money.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 197

Taxes on alcohol sales have been an indirect mechanism for regulating the consumption of alco- hol by increasing its price, not unlike taxes on tobacco products (see Chapter 10). More than $8 billion each year is collected from federal excise taxes on alcohol. Total annual revenues exceed $18 billion, when addi- tional excise taxes imposed by all U.S. states and some local communities are included. Today, alcoholic beverages are one of the most heavily taxed consumer products. Approximately 45 percent of the retail price of an average bottle of distilled spirits, for example, is earmarked for federal and state taxes.12

It has been proposed that alcohol taxes be set high enough to begin to offset the total societal costs resulting from alcohol abuse. This approach would place a type of “user fee” on the consumption of alcohol and reduce the prevalence of alcohol abuse. In general, studies inves- tigating the effects of price on drinking behavior have shown that increases in retail prices for alcoholic bever- ages have had a significant effect in reducing consump- tion both in the general population and high-risk groups such as heavy drinkers, adolescents, and young adults.13

Patterns of Alcohol Consumption Today

It has been theorized that the earliest systems of agricul- ture in human history were born of the desire to secure a dependable supply of beer.14 If this is so, then alcohol, commercialization, and economics have been linked from the very beginning. Today, of course, alcohol is not merely a big business but an enormous business. Ameri- cans spend more than $140 billion on the purchase of alcoholic beverages each year, and the alcohol industry spends about $1.7 billion advertising its products. In 2007, more than 40 percent of this advertising budget was devoted to television commercials for beer.15

Overall Patterns of Alcohol Consumption How much do Americans actually drink? The most recent estimate of the annual per capita consumption of pure alcohol for adults in the United States is approxi- mately 2.3 gallons (8.7 liters). This level of consumption amounts to about three-fourths of an ounce per day.16

How many alcoholic drinks does this estimated daily amount add up to? To answer this question, it is important first to consider the amount of pure alcohol that is contained in each of four basic types of alcoholic

beverages. A person consumes a half-ounce of alcohol when drinking any of the following alcoholic beverages:

■ One 5-ounce glass of wine ■ One 12-ounce bottle or can of beer ■ One 12-ounce bottle of wine cooler ■ One shot (1.5-ounce size) of 80-proof liquor

All these quantities are approximately equal to about one-half ounce in terms of pure alcohol, and they are often referred to as “standard drinks.”

Based on these equivalencies, the average alcohol consumption in the United States can be approximated as about 1.5 “standard drinks” per day. Bear in mind, however, that a “standard drink” may not be the drink you consume, so it is not necessarily the appropriate unit to use when computing your own personal level of alcohol consumption. Draft beer, for example, is typi- cally dispensed in large glasses that exceed 12 ounces in capacity. A mixed drink in a bar might contain a quantity of liquor that exceeds a standard amount, if the bartender is particularly generous. In either of these circumstances, an individual can be misled into believing that he or she is consuming an “average” amount (in terms of number of drinks) when, in fact, the quantity of alcohol being consumed is considerably larger (Health Line).

The stainless steel tanks of the world’s largest wine maker, the Ernest and Julio Gallo Winery, are located in Modesto, California. Nearly 900 million gallons of wine are produced by E. & J. Gallo each year, accounting for approximately one of every three bottles of wine sold annually in the United States.

198 ■ Part three Legal Drugs in Our Society

health Line Multiple Ways of Getting a Standard Drink

A standard alcoholic drink is any drink that contains about 14 grams of pure alcohol (about 0.5 fluid ounce). All of the following seven alcoholic drinks should be considered equivalently as a standard drink.

There are so many variations in the quantity of an alcoholic beverage being served that it can be confusing to deter- mine how many standard drinks are actually being consumed. Here are some examples of how the number of standard drinks can multiply when quantities increase:

■ For beer or wine cooler, the approximate number of standard drinks in • 12 oz = 1 • 16 oz = 1.3 • 22 oz = 2 • 40 oz = 3.3

■ For malt liquor, the approximate number of standard drinks in • 12 oz = 1.5 • 16 oz = 2 • 22 oz = 2.5 • 40 oz = 4.5

■ For table wine, the approximate number of standard drinks in • a standard 750 mL (25 oz) bottle = 5

■ For 80-proof spirits, or “hard liquor,” the approximate number of standard drinks in • a mixed drink = 1 or more† • a pint (16 oz) = 11 • a fifth (25 oz) = 17 • 1.75 L (59 oz) = 39

*In recent years it has been common for wines to contain an alcohol concentration of 16 percent. In these instances, 5 ounces of wine would be equivalent to 0.80 ounce of alcohol, which is 33 percent higher than when a 12 percent wine is considered. Another way of thinking about this is that for a drink of wine with 16 percent alcohol concentration to be equivalent to a 12-ounce can of beer or a typical shot of liquor, the quantity of wine consumed should be reduced to approximately 4 ounces. In this chapter, however, we will retain the concept of 5 ounces of wine as representing a standard drink, since it is traditional that alcohol equivalencies are calculated on this basis. †It can be difficult to estimate the number of standard drinks served in a single mixed drink made with hard liquor. Depending on factors such as the type of spirits and the recipe, one mixed drink can contain from one to three or more standard drinks.

Source: National Institute on Alcohol Abuse and Alcoholism (2005). Helping patients who drink too much: A clinician’s guide. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism, p. 12.

12 oz 8.5 oz 5 oz 3.5 oz 2.5 oz 1.5 oz 1.5 oz

1.5 oz of spirits

(a single jigger of 80-proof gin, vodka,

whiskey, etc.) Shown straight and in a highball glass with ice to show

level before adding mixer †

2–3 oz of cordial,

liqueur, or aperitif

2.5 oz shown

3–4 oz of forti�ed wine

(such as sherry or

port) 3.5 oz shown

5 oz of table wine*

8–9 oz of malt liquor 8.5 oz shown in

a 12 oz glass that, if full, would hold

about 1.5 standard drinks of

malt liquor

12 oz of beer or

wine cooler

1.5 oz of brandy

(a single jigger)

Chapter 8 alcohol: Social Beverage/Social Drug ■ 199

Another consideration when looking at statistics based on population averages is the obvious fact that not everyone is “average.” There is an enormous dispar- ity in terms of how much alcohol each person actually consumes during a given year. Some people drink no alcohol at all, whereas others drink heavily. In fact, 80 percent of the total amount of alcohol consumed in the United States each year is consumed by only the 30 per- cent of Americans who drink—and by only 20 percent

of the population (includes non-drinkers) in general. Drugs . . . in Focus, shown below, provides a concrete illustration of the extremely uneven pattern of alcohol consumption in the United States today.

Looking at the types of alcohol consumed in the United States, beer consumption represents about 67 percent of overall alcoholic consumption and a dis- proportionate share of heavy alcohol drinking. When five or more 12-ounce beers are consumed in a day,

Drugs . . . in Focus

Visualizing the Pattern of Alcohol Consumption in the United States To appreciate the uneven pattern of alcohol consumption in the population, try the following demonstration:

Assemble ten people and ten bottles of beer (preferably empty). Separate three people who hold nothing. They rep- resent the 30 percent of the population that does not drink alcohol at all. Separate five people; together they hold two bottles. They represent the 50 percent of the population that drinks 20 percent of the total alcohol supply. Separate the ninth person; this person holds two bottles. This individual represents the 10 percent of the popula- tion that drinks another 20 percent of the total alcohol supply. Separate the tenth person; this person holds a six-pack of bottles. This individual represents the 10 percent of the population that drinks 60 percent of the total alco- hol supply.

The Moral of the Story Twenty percent of the entire population (the ninth and tenth persons in this demonstration) drink 80 percent of the total alcohol consumed in the United States each year. Of those who drink some alcohol, two-sevenths (roughly 30 percent) of them drink 80 percent of the total alcohol consumed each year, while five-sevenths (roughly 70 percent) of them drink the remaining 20 percent. These figures correspond to those expressed in the text.

Figure, p. 30, “A Tale of 10 Beers and 10 People” from Loos- ening the Grip: A Handbook of Alcohol Information (8th ed.) by J. Kinney. Copyright © 2006. Reprinted by permission of The McGraw-Hill Companies.

200 ■ Part three Legal Drugs in Our Society

there is a stronger association with alcohol-related prob- lems than when there are comparable consumption lev- els of wine or liquor. We can conclude that beer is the most problematic form of alcohol consumption in the United States today.17

Problematic Alcohol Consumption among College Students Not surprisingly, the prevalence of moderate alcohol consumption in college (assessed in terms of those hav- ing a drink in the last thirty days) is substantially higher than levels encountered in high school (see Chapter 1), although the establishment of twenty-one as the man- dated legal drinking age in all U.S. states has delayed the occurrence of peak consumption levels to the junior or senior year. Among young adults, binge drinking— defined for men as having five or more alcoholic drinks and for women as having four or more alcoholic drinks over a period of two hours—rises sharply from age eigh- teen to a prevalence rate of about 28 percent (one in four) among those 18 to 35 years of age. For adults of all ages, the prevalence rate is about 17 percent (one in six).

An extensive series of surveys conducted from 1993 to 2005 on American college campuses have shown a fairly consistent picture of the problematic alcohol con- sumption of college students in the United States over this period of time. Here are the general findings:

■ Overall, approximately 44 percent of college students report having engaged in binge drinking during the two weeks prior to the administration of the survey— 41 percent of the women and 49 percent of the men. About one in five students abstains from alcohol, whereas one in four is a frequent binge drinker. About half of college students (48 percent) report that drink- ing to get drunk is an important reason for drinking. Three students in ten (29 percent) report being intoxi- cated three or more times in a month.

■ College students who drank alcohol at some time over the past year frequently report alcohol-related problems while at college. One in four students re- port that their drinking had a negative impact on their academic performance. Problems included missing a class, falling behind on course assignments, doing poorly on exams or papers, and receiving lower grades overall.

■ One in five students report that, while intoxicated, they engaged in unplanned sexual activity or engaged in unprotected sex. One in three students report that they had done something they regretted while intoxicated.

The surveys have also shed light on the adverse impact of alcohol consumption among college students on nondrinkers (defined as either abstainers or nonbinge drinkers). These situations, called secondhand effects (because the individuals themselves were not intoxi- cated but were affected by those who were), are analo- gous to the problems of secondhand smoking, which will be examined in Chapter 10. Three in 10 college students (29 percent) report that they were insulted or humiliated by another student who had been drinking. One in five students (19 percent) report having experi- enced an unwanted sexual advance.

It is estimated that approximately 700 college stu- dents between the ages of 18 and 24 die each year from alcohol-related unintentional injuries, principally as a consequence of motor vehicle accidents. The trend toward lower levels of high-risk drinking on college campuses will be reviewed in Chapter 16 in the context of overall substance-abuse prevention.18

Alcohol Consumption among Adolescents Among young people who report some alcohol con- sumption between the ages of twelve and twenty, the average age when drinking began is fourteen years. In the 2011 University of Michigan survey, 33 percent of eighth graders reported that they had consumed alcohol, and 15 percent reported that they had been drunk sometime in their lives. Fortunately, these fig- ures are down significantly when compared to earlier surveys. Approximately 6 percent of students at this age reported consuming more than five drinks on a single occasion in the previous two weeks, a pattern of

Binge drinking among college students and other young adults is a common social ritual as well as a continuing social concern.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 201

behavior that is about one-half the percentage reported in the late 1990s.

The major challenge in reducing underage alcohol use has been the continuing access that underage drink- ers have to alcoholic beverages, despite the present legal restrictions on alcohol sales. Studies show that more than 40 percent of the estimated 11 million underage drinkers, defined as persons aged twelve to twenty who drank in the past 30 days, were provided free alcohol by adults twenty-one or older. About 6 percent of under- age drinkers were given alcohol by their parents in the past month. A majority (54 percent) reported drinking alcohol in someone else’s home, and 30 percent drank in their own home.19

The Pharmacology of Alcohol

Alcohol is a very small molecule that is moderately soluble in fat and highly soluble in water—all charac- teristics that make it easily absorbed through the gas- trointestinal tract once it is ingested, without needing any digestion. About 20 percent of it is absorbed into the bloodstream directly from the stomach, whereas the remaining 80 percent is absorbed from the upper por- tion of the small intestine.

On entering the stomach, alcohol acts initially as an irritant, increasing the flow of hydrochloric acid and pepsin, chemicals that aid digestion. Therefore, in small amounts, alcohol can help digest a meal. In large amounts, however, alcohol irritates the stomach lining. This is a concern for those already having stomach prob- lems; preexisting ulcers are worsened by drinking alco- hol, and heavy alcohol drinking can produce ulcers.

The irritating effect on the stomach explains why the alcohol proceeds on to the small intestine more quickly when alcohol concentrations are high. The stomach is simply trying to get rid of its irritant. Over time, the chronic consumption of alcohol can produce an inflammation of the stomach (gastritis) or the pan- creas (pancreatitis).

Because the small intestine assumes the major share of the responsibilities and acts extremely rapidly (more rapidly than the stomach), the rate of total alcohol absorp- tion is based largely on the condition of the stomach when the alcohol arrives and the time required for the stomach to empty its contents into the small intestine. If the stomach is empty, an intoxicating effect (the “buzz”) will be felt very quickly. If the stomach is full, absorption will be delayed as the alcohol is retained by the stomach along with the food being digested, and the passage of alcohol into the small intestine will slow down.

Besides the condition of the stomach, there are other factors related to the alcohol itself and the behavior of the drinker that influence the rate of alcohol absorp- tion. The principal factor is the concentration of alcohol in the beverage being ingested. An ounce of 80-proof (40 percent) alcohol will be felt more quickly than an ounce of wine containing 12 percent alcohol, and of course the level of alcohol in the blood will be higher as well. Also, if the alcoholic beverage is carbonated, as are champagne and other sparkling wines, the stomach will empty its contents faster and effects will be felt sooner. Finally, if the alcohol enters the body at a rapid pace, such as when drinks are consumed in quick succession, the level of alcohol in the blood will be higher because the liver cannot eliminate it fast enough. All other factors being equal, a bigger person requires a larger quantity of alcohol to have equivalent levels accumulating in the blood, simply because there are more body fluids to absorb the alcohol, thus diluting the overall effect.20

The Breakdown and Elimination of Alcohol Its solubility in water helps alcohol to be distributed to all bodily tissues, with those tissues having greater water content receiving a relatively greater proportion

Quick Concept Check 8.1

Understanding Alcoholic Beverages Check your understanding of the alcohol content of various types of alcoholic beverages by rank ordering the alcohol content of the following five “bar orders,” with 1 representing the largest amount and 5 the smallest. Are there any ties?

_______ A. three 1-shot servings of liquor and one 5-oz glass of wine

_______ B. two 1-shot servings of liquor

_______ C. one 1-shot serving of liquor, one 5-oz glass of wine, and three 12-oz beers

_______ D. three 5-oz glasses of wine

_______ E. one 1-shot serving of liquor, one 5-oz glass of wine, and one 12-oz beer

Answers: 1 = C 2 = A 3 = D and E (tie) 5 = B

202 ■ Part three Legal Drugs in Our Society

of alcohol. The excretion of alcohol is accomplished in two basic ways. About 5 percent will be eliminated by the lungs through exhalation, causing the charac- teristic “alcohol breath” of heavy drinkers. Breathalyz- ers, designed to test for alcohol concentrations in the body and used frequently by law-enforcement officers to test for drunkenness, work on this principle. The remaining 95 percent is eliminated in the urine after the alcohol has been biotransformed into carbon diox- ide and water.21

The solubility of alcohol in fat facilitates its pas- sage across the blood–brain barrier (see Chapter 3). As a result, approximately 90 percent of the alcohol in the blood reaches the brain almost immediately. Unfortu- nately, alcohol passes the blood–placenta barrier with equal ease, so alcohol intake by women during preg- nancy affects the developing fetus. As a result, fetal alcohol levels are essentially identical to those of the mother who is drinking.22 This important matter will be discussed in the next chapter, when we consider a type of mental and physical retardation called fetal alcohol syndrome.

The body recognizes alcohol as a visitor with no real biological purpose. It contains calories but no vita- mins, minerals, or other components that have any nutritional value. Therefore, the primary bodily reac- tion is to break it down for eventual removal, through a process called oxidation. This biotransformation process consists of two basic steps. First, an enzyme, alcohol dehydrogenase breaks down alcohol into acetaldehyde. This enzyme is present in the stomach, where about 20 percent of alcohol is broken down prior to absorption into the bloodstream, and in the liver, where the remaining 80 percent is broken down from accumulations in the blood. Second, another enzyme, acetaldehyde dehydrogenase, breaks down acetalde- hyde in the liver into acetic acid. From there, further

oxidation results in oxygen, carbon dioxide, and calo- ries of energy.

The entire process is determined by the speed with which alcohol dehydrogenase does its work, and for a given individual, it works at a constant rate, no matter how much alcohol needs to be broken down. Imagine a bank at which only one teller window stays open, no matter how long the line of customers grows, and you will understand the limitations under which the body is operating.

The specific rate of oxidation is approximately 100 milligrams of alcohol per hour per kilogram of body weight. To put this in perspective, 8 grams of alcohol will be broken down in an hour if you weigh 176 pounds (80 kilograms), and 5 grams of alcohol will be broken down in an hour if you weigh 110 pounds (50 kilograms). Certain conditions and circumstances, however, can alter this basic biotransformation rate (Health Line).

In terms of alcoholic beverages, the oxidation rate for adults in general is approximately one-third to one- half ounce of pure alcohol an hour. If you sipped (not gulped) slightly less than the contents of one 12-ounce bottle of beer, one 5-ounce glass of wine, or any equiva- lent portion of alcohol very slowly over an hour’s time, the enzymes in the stomach and liver would keep up, and you would not feel intoxicated. Naturally, if you consume larger amounts of alcohol at faster rates of con- sumption, all bets are off.23

It is no secret that alcohol consumption is condu- cive to the accumulation of body fat, most noticeably in the form of the notorious beer belly. It turns out that alcohol does not have significant effects on the bio- transformation of dietary carbohydrates and proteins, so a drinking individual who consumes a healthy diet does not have to worry about getting enough nutri- ents. Alcohol does, however, reduce the breakdown of fat, so dietary fat has a greater chance of being stored rather than expended. Over time, the accumulation of fat in the liver is particularly serious because it eventu- ally interferes with normal liver function. The poten- tially life-threatening medical conditions involving the liver will be examined in the next chapter as a prime example of the adverse effects of chronic alcohol consumption.24

Measuring Alcohol in the Blood Alcohol levels in the blood, like levels of any drug, vary considerably not only by virtue of how much is ingested and how long ago, but also as a result of differences in an individual’s body size and relative

oxidation: A chemical process in alcohol metabolism. alcohol dehydrogenase (Al-co-haul Dee-high- DrAW-juh-nays): An enzyme in the stomach and liver that converts alcohol into acetaldehyde.

acetaldehyde (ASS-ee-TAl-duh-hide): A by-product of alcohol metabolism, produced through the action of alcohol dehydrogenase.

acetaldehyde dehydrogenase (ASS-ee-TAl-duh- hide Dee-high-DrAW-juh-nays): An enzyme in the liver that converts acetaldehyde to acetic acid in alcohol metabolism.

acetic acid (a-See-tik ASS-id): A by-product of alcohol metabolism, produced through the action of acetaldehyde dehydrogenase.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 203

proportions of body fat. Consequently, we have to con- sider a specific ratio referred to as the blood-alcohol concentration (BAC) when assessing physiological and psychological effects (an alternative term is blood- alcohol level).

The BAC refers to the number of grams of alco- hol in the blood relative to 100 milliliters of blood, expressed as a percentage. For example, 0.1 gram (100 milligrams) of alcohol in 100 milliliters of blood is represented by a BAC of 0.10 percent. Table 8.2 (page 204) shows the BAC levels that can be esti- mated from one’s body weight, number of standard drinks consumed, and hours elapsed since starting the first drink.

From these figures, BAC levels typically are con- sidered in terms of three broad categories of behavior: caution (0.01 to 0.05 percent), driving impaired (0.05 to 0.08 percent), and legally drunk (in all U.S. states, 0.08 percent and higher). In effect, you need to compute the accumulated BAC levels for your specific body weight after having a specific number of drinks, and then sub- tract 0.015 percent BAC for each hour since the drink- ing occurred.25

blood-alcohol concentration (bAc): The number of grams of alcohol in the blood relative to 100 milliliters of blood, expressed as a percentage.

health Line Gender, Race, and Medication: Factors in Alcohol Metabolism

Since enzymes play such a critical role in alcohol break- down, it is important to consider factors that alter the lev- els of these enzymes. As mentioned in Chapter 3, two of these factors are gender and ethnicity. In general, women have about 60 percent less alcohol dehydrogenase in the stomach than men; thus their oxidation of alcohol is rela- tively slower, even when different body weights have been taken into account.

In addition, about 50 percent of all people of Asian descent have a genetically imposed lower level of acet- aldehyde dehydrogenase in the liver. As a consequence, acetaldehyde builds up, causing nausea, itching, facial flushing, and cardiac acceleration. The combination of these symptoms, often referred to as fast-flushing, makes alcohol consumption very unpleasant for many Asians.

It would be reasonable to expect, then, that those who experienced fast-flushing would drink less alcohol than those who do not. This is true when you look at the population at large. For Japanese American college students who have to contend with peer pressure to drink, however, the relationship between the physiological response and the quantity of alcohol consumed is not nearly as strong. For them, environmental factors encour- age alcohol consumption, despite their genetically deter- mined predisposition to get sick. In a similar way, the social life of Japanese businessmen has promoted alcohol consumption, even though many get sick as a result. Unfortunately, accepting an offer from one’s boss to go out drinking is part of the social networking required for corporate advancement.

Medications also can influence alcohol break- down by altering levels of alcohol dehydrogenase in the

stomach. Aspirin, for example, when taken on a full stom- ach, reduces enzyme levels by one-half, causing more alcohol to accumulate in the blood. Among women, aspirin has a greater inhibiting effect than among men, so it is possible that enzyme levels may be reduced to nearly zero if a woman is taking aspirin prior to drinking alco- holic beverages. Gastric ulcer medications also inhibit alcohol dehydrogenase and thus increase the physiologi- cal impact of alcohol. Any combination of these factors appears to produce additive effects. (See Table 8.3 on page 207 for other examples of alcohol-medication interactions.)

Sources: Edenberg, H. J. (2007, Winter). The genetics of alcohol metabolism: Role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Research and Health, 5–37. Frezza, M.; DiPadova, C.; Pozzato, G.; Terpin, M.; Baraona, E.; and Lieber, C. S. (1990). High blood alcohol levels in women: The role of decreased gastric alcohol dehydrogenase activ- ity and first-pass metabolism. New England Journal of Medicine, 322, 95–99. Nakawatase, T. V., and Sasao, T. (1993). The association between fast-flushing response and alcohol use among Japanese Americans. Journal of Studies on Alcohol, 54, 48–53. Roine, R.; Gentry, T.; Hernandez-Muñoz, R.; Baraona, E.; and Lieber, C. S. (1990). Aspirin increases blood alcohol concentrations in humans after ingestion of ethanol. Journal of the American Medical Association, 264, 2406–2408. Scott, D. M., and Taylor, R. E. (2007, Winter). Health-related effects of genetic variations of alcohol-metabolizing enzymes in African Americans. Alcohol Research and Health, 18–21.

204 ■ Part three Legal Drugs in Our Society

Effects of Alcohol on the Brain

Alcohol is clearly a CNS depressant drug, though it is often misidentified as a stimulant. The reason for this confusion is that alcohol, at low doses, first releases the cerebral cortex from its inhibitory control over subcor- tical systems in the brain, a kind of double-negative effect. In other words, alcohol is depressing an area of the brain that normally would be an inhibitor, and the result of this “disinhibition” is the illusion of stimula- tion. The impairment in judgment and thinking (the classic features of being drunk) stems from a loosening of social inhibitions that enable us, under nonalcoholic circumstances, to be relatively thoughtful about the consequences of our actions, as well as relatively civil and well behaved.26

As the BAC level increases, the depressive action of alcohol extends downward to lower regions of the brain. Eventually, an inhibition of the respiratory centers in the medulla becomes a distinct possibility, leading to asphyxi- ation (a loss of breathing). In general, neuronal inhibition is linked to the effect of alcohol on the GABA receptor in the brain. Imagine this receptor as having three com- ponents: one sensitive specifically to the neurotransmitter

GABA, one sensitive to barbiturates, and one sensitive to a type of antianxiety medication (see Chapter 13). The last component is also sensitive to alcohol, and the research suggests that alcohol acts at this site, making it more difficult for the neuron to be stimulated.27

More worrisome than alcohol’s depressive effects on the brain, however, is its ability to set up a pattern of psy- chological dependence. Since the late 1980s, evidence has accumulated that the reinforcing action of alcohol is a result of its influence on dopamine-releasing neurons in the nucleus accumbens of the brain (see Chapter 3). The fact that alcohol shares this effect with other abused drugs, including heroin, cocaine, and nicotine, suggests that treatments for one form of drug abuse can be effec- tive for others. Chapter 9 describes the recent research concerning the use of naltrexone, an opioid antagonist, in the treatment of chronic alcohol abuse.28

Acute Physiological Effects

Alcohol can produce a number of acute physiological effects; they will be examined here. The physiological effects resulting from chronic alcohol consumption will be covered in the next chapter.

TAble 8.2

When are you drunk? Calculating your blood-alcohol concentration (BAC) level

Standard Drinks

1 2 3 4 5 6 7 8 9 10

100 .029 .058 .088 .117 .146 .175 .204 .233 .262 .290

W eI

g H

T (l

b )

120 .024 .048 .073 .097 .121 .145 .170 .194 .219 .243

140 .021 .042 .063 .083 .104 .125 .146 .166 .187 .208

160 .019 .037 .055 .073 .091 .109 .128 .146 .164 .182

180 .017 .033 .049 .065 .081 .097 .113 .130 .146 .162

200 .015 .029 .044 .058 .073 .087 .102 .117 .131 .146

220 .014 .027 .040 .053 .067 .080 .093 .106 .119 .133

240 .012 .024 .037 .048 .061 .073 .085 .097 .109 .122

CAUTION DRIVING IMPAIRED LEGALLy DRUNK

Alcohol is “burned up” by your body at .015% per hour, as follows:

Hours since starting first drink 1 2 3 4 5 6 Percent alcohol burned up .015 .030 .045 .060 .075 .090

To calculate your BAC level correctly, you must consider the number of standard drinks you have consumed, your body weight, and how much time has passed since the first drink. Note that a BAC level of .10% or higher has been, until recently, the standard for drunk driving in most U.S. states. All U.S. states have now adopted the .08% standard.

Source: Updated from A primer of drug action, 8th ed., by R. M. Julien, M.D. © 2001 Worth Publishers. Used with permission.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 205

Toxic Reactions First and foremost, we need to be aware of the risk of death by asphyxiation if BAC levels are elevated, gen- erally when they reach 0.50 percent. The therapeutic index for alcohol, as measured by the LD50/ED50 ratio (see Chapter 2), is approximately 6, which is not a very high number. Therefore, caution is strongly advised; the risks of being the “big winner” in a drinking contest should be weighed very carefully. On the one hand, to achieve a lethal BAC level of 0.50 percent, a 165-pound man needs to have consumed approximately twenty- three drinks over a four-hour period.29 On the other hand, consuming “merely” ten drinks in one hour, a drinking schedule that achieves a BAC level of 0.35 per- cent, puts a person in extremely dangerous territory. It is important to remember that LD50 is the average level for a lethal effect; there is no way to predict where a par- ticular person might be located on the normal curve.

Fortunately, two physiological mechanisms are designed to protect us to a certain degree. First, alco- hol acts as a gastric irritant, so the drinker often feels nauseated and vomits. Second, the drinker may simply

pass out, and the risk potential from further drinking becomes irrelevant. Nonetheless, there are residual dan- gers in becoming unconscious; vomiting while in this state can prevent breathing, and death can occur from asphyxiation (Health Alert).

Heat Loss and the Saint Bernard Myth Alcohol is a peripheral vasodilator, which means that blood vessels near the skin surface enlarge, leading to a greater amount of blood shunted to the skin. The effect gives you the feeling that your skin is warm, which is probably the basis for the myth that alcohol can keep you warm in freezing weather. In truth, however, peripheral dilation causes core body temperature to decrease. In other words, alcohol produces a greater loss in body heat than would occur without it. So if you are marooned in the snow and you see an approaching Saint Bernard with a cask of brandy strapped to its neck, refuse the offer. It will not help and could very well do you harm. (But feel free to hug the dog—that will certainly help.)

H e A l T H A l e r T !

emergency Signs and Procedures in Acute Alcohol Intoxication Emergency Signs • Stupor or unconsciousness • Cool or damp skin • Weak, rapid pulse (more than 100 beats per minute) • Shallow and irregular breathing rate, averaging around

one breath every three or four seconds • Pale or bluish skin

Note: Among African Americans, color changes will be apparent in the fingernail beds, mucous membranes inside the mouth, or underneath the eyelids.

Emergency Procedures • Seek medical help immediately. • Drinker should lie on his or her side, with the head

slightly lower than the rest of the body. This will prevent blockage of the airway and possible asphyxia- tion if the drinker starts to vomit.

• If drinker is put to bed, maintain some system of moni- toring until he or she regains consciousness.

Note: There is no evidence that home remedies for “sobering up,” such as cold showers, strong coffee, forced activity, or induction of vomiting, have any effect in reducing the level of intoxication. The only factors that help are the passage of time, rest, and perhaps an analgesic if there is a headache.

Where to go for assistance: www.emedicinehealth.com/alcohol_intoxication/ article_em.htm.

This web site provides consumer health information on a variety of issues related to acute alcohol intoxica- tion. It is owned and operated by WebMD and is part of the WebMD network.

Source: Victor, M. (1976). Treatment of alcohol intoxication and the withdrawal syndrome: A critical analysis of the use of drugs and other forms of therapy. In P. G. Bourne (Ed.), Acute drug abuse emergencies: A treatment manual. New york: Academic Press, pp. 197–228.

206 ■ Part three Legal Drugs in Our Society

Diuretic Effects As concentration levels rise in the blood, alcohol begins to inhibit antidiuretic hormone (ADH), a hormone that normally acts to reabsorb water in the kidneys prior to elimination in the urine. As a result, urine is more diluted and, because large amounts of liquid are typi- cally being consumed at the time, more copious. Once blood-alcohol concentrations have peaked, however, the reverse occurs. Water is now retained in a condition called antidiuresis, resulting in swollen fingers, hands, and feet. This effect is more pronounced if salty foods (peanuts or pretzels, for example) were eaten along with the alcohol.

The inhibition of ADH during the drinking of alco- holic beverages can be a serious concern, particularly following vigorous exercise when the body is already suffering from a loss of water and fluid levels are low. Therefore, the advice to the marathoner, whose body may lose more than a gallon of water over the course of a warm three-hour run, is to celebrate the end of the race not with a beer but with nonintoxicating liquids such as Gatorade or similar mineral-rich drinks.30

Effects on Sleep It might seem tempting to induce sleep with a relaxing “nightcap,” but in fact the resulting sleep patterns are adversely affected. Alcohol reduces the duration of a phase of sleep called rapid eye movement (REM) sleep (see Chapter 13). Depending on the dose, REM sleep can be either partially or completely suppressed dur- ing the night. When alcohol is withdrawn, REM sleep rebounds and represents a higher percentage of total sleep time than before alcohol consumption began. As a result, individuals sleep poorly and experience nightmares.31

Effects on Pregnancy The consumption of alcohol during pregnancy, even in moderation, greatly increases the risk of retardation in the development of the fetus (a serious condition called fetal alcohol syndrome, see Chapter 9), and reducing the incidence of this behavior has been a major pub- lic health objective since the mid-1990s. From data

averaged over 2010 and 2011, it has been estimated that about 9 percent of pregnant women consume alcohol during the past month at some time during their preg- nancy, exposing approximately one in eleven fetuses to alcohol in utero. National public health goals for the United States (see Chapter 17) have included a reduc- tion of this percentage to 6 percent, an objective that may be achieved in the next decade, given the steady progress being made in this regard. It is fortunate that even relatively brief interventions are effective in help- ing pregnant women achieve abstinence from alcohol. In one program of this kind, women were five times more likely to have abstained by the third trimester of pregnancy, relative to controls, after a brief (10 to 15 minute) counseling session in a walk-in center.32

Interactions with Other Drugs A major concern in alcohol drinking is the complex interaction of alcohol with a wide range of drugs. As noted in Chapter 2, the DAWN reports of emergency department admissions and deaths show a significant incidence of medical crises arising from the combina- tion of alcohol not only with prescribed medications but also with virtually all the illicit drugs on the street. Opi- oid drugs, marijuana, and many prescription medicines interact with alcohol such that the resulting combina- tion produces effects that are either the sum of the parts or greater than the sum of the parts. In other cases, the ingestion of medication with alcohol significantly less- ens the medication’s benefits. Anticoagulants, anticon- vulsants, and monoamine oxidase inhibitors (used as antidepressants) fit into this second category. Table 8.3 shows a partial listing of major therapeutic drugs that interact with alcohol and have undesirable, if not dan- gerous, outcomes. Given the length of a complete listing, it is fair to say that, whenever any medication is taken, the individual should inquire about possible interactions with alcohol.

Hangovers About four to twelve hours after heavy consumption of alcohol, usually the next day, unpleasant symptoms of headache, nausea, fatigue, and thirst may occur; these are collectively known as a hangover. At least one such experience has been undergone by 40 percent of all men and 27 percent of all women over the age of eigh- teen.33 Why these symptoms occur is not at all clear. The probable explanations at present focus on individ- ual aspects of a hangover, though it is likely that several factors contribute to the total phenomenon.

antidiuretic hormone (ADH): A hormone that acts to reabsorb water in the kidneys prior to excretion from the body.

antidiuresis: A condition resulting from excessive reabsorption of water in the kidneys.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 207

One factor, beyond the simple fact of drinking too much, is the type of alcohol that has been consumed. Among distilled spirits, for example, vodka has a lower probability of inducing hangovers than whiskey. A pos- sible reason is the relatively lower amount of congeners. These substances in alcoholic beverages, including trace amounts of nonethyl alcohol, oils, and other organic matter, are by-products of the fermentation and distillation processes and give the drinks their distinctive smell, taste, and color. A common congener is the tan- nin found in red wines. Although no harm is caused by congeners in minute concentrations, they are still toxic substances, and they probably contribute to hangover symptoms.34

Other possible factors include traces of nonoxi- dized acetaldehyde in the blood, residual irritation in the stomach, and a low blood sugar level rebounding from the high levels induced by the previous ingestion

of alcohol. The feeling of swollenness from the anti- diuresis, discussed earlier, may contribute to the head- ache pain. The thirst may be due to the dehydration that occurred the night before.

Acute Behavioral Effects

The consumption of alcoholic beverages is so perva- sive in the world that it seems almost unnecessary to comment on how it feels to be intoxicated by alcohol. The behavioral effects of consuming alcohol in more than very moderate quantities range from the relatively

TAble 8.3

A partial listing of possible drug-alcohol interactions

generIc Drug (brAnD nAMe or TYPe)

conDITIon beIng TreATeD

eFFecT oF InTerAcTIon

chloral hydrate (Noctec) Insomnia Excessive sedation that can be fatal; irregular heartbeat; flushing

glutethimide (Doriden) Insomnia Excessive sedation; reduced driving and machine-operating skills

antihypertensives (Apresoline, Diuril)

High blood pressure Exaggeration of blood pressure-lowering effect; dizziness on rising

diuretics (Aldactone) High blood pressure Exaggeration of blood pressure-lowering effect; dizziness on rising

antibiotics (penicillin) Bacterial infections Reduced therapeutic effectiveness

nitroglycerin (Nitro-bid) Angina pain Severe decrease in blood pressure; intense flushing; headache; dizziness on rising

warfarin (Coumadin) Blood clot Changes in the anti-blood clotting effect*

insulin Diabetes Excessive low blood sugar; nausea; flushing

disulfiram (Antabuse) Alcoholic drinking Intense flushing; severe headache; vomiting; heart palpitations; could be fatal

methotrexate Various cancers Increased risk of liver damage

phenytoin (Dilantin) Epileptic seizures Changes in drug effectiveness in preventing seizures*

prednisone (Deltasone) Inflammatory conditions (arthritis, bursitis)

Stomach irritation

various antihistamines Nasal congestion Excessive sedation that could be fatal

acetaminophen (Tylenol) Pain Increased risk of liver damage

Note: Warfarin effects and phenytoin effectiveness will be decreased among individuals who are regular alcohol drinkers, while warfarin effects and phenytoin effectiveness will be enhanced (with greater incidence of side effects) among individuals who ingest a few drinks or more immediately prior to taking the drug.

Sources: Brick, J.; Wallen, M. C.; and Lorman, W. J. (2008). Interaction of alcohol with medications and other drugs. In J. Brick (Ed.), Handbook of the medical consequences of drug and alcohol abuse (2nd ed.). New york, Routledge, pp. 527–563. National Institute on Alcohol Abuse and Alcoholism (1995, January). Alcohol alert: Alcohol–medication interactions. No. 27, PH355. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism.

congeners (Kon-jen-ers): Nonethyl alcohols, oils, and other organic substances found in trace amounts in some distilled spirits.

208 ■ Part three Legal Drugs in Our Society

harmless effects of exhilaration and excitement, talk- ativeness, slurred speech, and irritability to behaviors that have the potential for causing great harm: uncoor- dinated movement, drowsiness, sensorimotor difficul- ties, and stupor.35 Some of the prominent behavioral problems associated with acute alcohol intoxication will be examined in this section.

Blackouts A blackout is an inability to remember events that occurred during the period of intoxication, even though the individual was conscious at the time. For example, a drinker having too much to drink at a party drives home, parks the car on a nearby street, and goes to bed. The next morning, he or she has no memory of having driven home and cannot locate the car. This phenom- enon is different from “passing out,” which is a loss of consciousness from alcoholic intoxication. In the case of blackouts, consciousness is never lost. Essentially, the alcohol is suppressing specific areas of the brain that are normally responsible for the formation of long-term memory.

Owing to the possibility of blackouts, drinkers can be easily misled into thinking that because they can understand some information given to them dur- ing drinking, they will remember it later. The risk of blackouts is greatest when alcohol is consumed very quickly, forcing the BAC to rise rapidly. In a recent e-mail survey of college students to learn more about their experiences with blackouts, approximately half of those who had ever consumed alcohol reported having experienced a blackout at some point in their lives, and 40 percent reported having had at least one experience in the twelve months prior to the survey.36

Driving Skills There is no question that alcohol consumption sig- nificantly impairs the ability to drive or deal with auto- mobile traffic, particularly among young people. In 2011, of the 32,367 traffic fatalities that occurred in the United States, 9,878 of them (about 31 percent) were alcohol-related. To put this statistic in perspective, there were approximately 27 alcohol-impaired driving fatalities every day during that year (one instance every 53 minutes).37

Officially, statistics about alcohol-related fatalities are based on conditions in which drivers had a BAC of 0.08 percent or higher, the minimum standard for legal intoxication in all U.S. states, but there were also a number of fatalities resulting from a BAC below that level. It is important to recognize that driving can be impaired and an accident can occur with BAC levels as low as 0.20 to 0.40 percent—well below the “driving while intoxicated” (DWI) threshold.

All these statistics could be viewed as correla- tional, and not necessarily as proof of a causal rela- tionship between alcohol and automobile accidents, were it not for the data from laboratory-based experi- ments showing a clear deterioration of sensorimotor skills following the ingestion of alcohol. Reaction times are slower, the coordination necessary to steer a car steadily is hampered, and the ability to stay awake when fatigued is impaired, but the major way that alcohol impairs driving ability is by reducing the drinker’s awareness of peripheral events and stimuli.38 One researcher in this area has expressed the deficit in this way:

The overwhelming majority of accidents involving alcohol are not accidents in which tracking is the prime error. Contrary to what most people think, it isn’t that people are weaving down the road, which is a sign of very high blood alcohol levels; it’s that they have failed to see something. They go through a red light, they fail to see a pedestrian or a motor- cyclist, they fail to see that the road is curving. Their perceptual and attentive mechanisms are affected very early, after just one drink. These are the things that are the prime causes of accidents.39

blackout: Amnesia concerning events occurring during the period of alcoholic intoxication, even though con- sciousness had been maintained at that time.

Every community has its tragic stories of preventable deaths due to drunk driving. Alcohol is also recognized as a major factor in more than 800 boating fatalities in the United States each year.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 209

Unfortunately, it is the weaving behavior, or other extreme examples of driving impairments, that most often signals the police to stop a car for a possible DWI violation; other alcohol-based impairments frequently go unnoticed until it is too late.

Preventing Alcohol-Related Traffic Fatalities among Young People

Increasing the minimum age for alcohol sales and standardizing the minimal BAC level for intoxicated driving have had a major impact on the likelihood of traffic fatalities among young people.40 Now that the minimum legal drinking age is set at twenty-one years and the minimum BAC level for intoxication lowered to 0.08 percent nationwide, there is reason to be cautiously optimistic. According to estimates made by the National

Highway Traffic Safety Administration, the reduction of the minimum BAC level to 0.08 percent has saved five hundred lives each year on the nation’s highways. More than 700 lives of persons aged eighteen, nineteen, or twenty have been saved each year as a result of laws setting twenty-one as the minimum drinking age. Since 1998, a nationwide minimum level of intoxication for drivers younger than twenty-one years of age has been set at a BAC level of 0.02 percent.41

Educational programs in schools and communities emphasizing the advantages of using “designated driv- ers,” as well as public education and lobbying groups such as Mothers Against Drunk Driving (MADD) and Students Against Drunk Driving (SADD), have had positive effects. This chapter’s Portrait feature highlights the origins and current aspirations of MADD.

A major goal in reducing alcohol-related fatalities on the road is to prevent an intoxicated individual from getting behind the wheel in the first place. We cannot prevent any intoxicated individual from driving a car,

P o r T r A I T Candace Lightner—Founder of MADD

In 1980, Candace Lightner’s thirteen-year-old daughter, Cari, was killed by a hit-and-run intoxicated driver in California. The driver had been out of jail on bail for only two days, a consequence of another hit- and-run drunk-driving crash, and he had three previous drunk-driving arrests and two previous convictions. He was allowed to plea bargain to vehicular manslaughter. Although the sentence was to serve two years in prison, the judge allowed him to serve time in a work camp and later a half- way house.

It was appalling to Lightner that drunk drivers, similar to the one who had killed her daughter, were receiv- ing such lenient treatment, with many of them never going to jail for a single day. Lightner quit her job and started an organization that has become a household name: Mothers Against Drunk Driving (MADD).

Since then, MADD has cam- paigned for stricter laws against drunk driving, and most of the present DWI

legislation around the country is a result of its intense efforts. In

addition, MADD acts as a voice for victims of drunk-driving injuries and the families of those who have been killed. From a single act of courage, despite enormous grief, Lightner cre- ated an organization that currently boasts more than 3 million members in the United States, with groups in virtually every state and more than four hundred local chapters.

Over the years, MADD has sought to reduce the number of alcohol- related traffic fatalities in a number of directions:

1. More effective enforcement of the minimum-drinking-age law.

2. A “0.00 percent BAC” criterion for drivers under twenty-one, making it illegal to drive with any measurable level of blood alcohol in any state.

3. Driver’s license suspensions for underage persons convicted of

purchasing or possessing alco- holic beverages.

4. Alcohol-free zones for youth gatherings.

5. Criminal sanctions against adults who provide or allow alcoholic beverages at events for underage participants.

6. Mandatory alcohol and drug testing for all drivers in all traffic crashes resulting in fatalities or serious bodily injury.

7. Sobriety checkpoints to detect and apprehend alcohol-impaired drivers and to serve as a visible deterrent to drinking and driving.

Its most recent success has been in the establishment of laws mandating the installation of ignition interlock systems in vehicles driven by individu- als convicted of drunk driving in all 50 U.S. states (see page 210).

Sources: Information courtesy of Mothers Against Drunk Driving, Dallas, Texas, 2012. Interview with Candace Lightner.

210 ■ Part three Legal Drugs in Our Society

but we can at least try to prevent an individual who has had a previous DUI arrest from driving while intoxicated. The most widely used technology for preventing such a situation is known as an ignition interlock device. When activated by the detection of a minimum BAC level in the breath of the driver, the ignition interlock will prevent the car from starting. When New Mexico became the first state to require ignition interlocks to be installed after a first DWI offense; alcohol-related fatalities decreased 11 percent in the first year. When Maryland mandated that the system be installed after several DWI arrests, fatalities were reduced by 18 percent. All 50 U.S. states have now enacted some form of ignition interlock law, typically during the period of license suspension and/or a specified time before fully relicensing DWI offenders. Several states mandate the installation of ignition inter- lock devices even after a first-time DWI offense.42

In general, even though we have reason to be some- what hopeful about reducing alcohol-related traffic fatalities, it is clear that much work remains to be done. The United States presently has one of the most lenient standards for driving while intoxicated among nations in the world (Table 8.4). The number of alcohol-related accidents, particularly among male drivers, whose involvement exceeds that of female drivers by about 2:1, is far too high. Meanwhile, the drinking-and-driving phenomenon is widespread throughout the population. In 2011, approximately 29 million drivers (one in nine drivers in the United States) admitted to driving a motor vehicle over the past year when they thought they were over the legal limit for alcohol and driving. The peak age among males reporting that they were drinking and driving was between 21 and 25, during which approxi- mately at least one in five reported being intoxicated on the road in the past year. Not surprisingly, automobile insurance premiums are considerably elevated for this demographic group.43

Alcohol, Violence, and Aggression It is difficult to avoid sweeping generalizations when confronted with statistics about alcohol and violent behavior both in the United States and around the world (see Chapter 2). In a major study conducted in a community in northwestern Ontario, Canada, and reported in 1991, more than 50 percent of the most recent occasions of physical violence were found to be preceded by alcohol use on the part of the assailant and/ or the victims themselves.44 Other studies show from 50 to 60 percent of all murders being committed when the killer had been drinking. About 40 percent of all acts of male sexual aggression against adult women and from 60 to 70 percent of male-instigated domestic vio- lence occur when the offender has been drunk; more than 60 percent of all acts of child molestation involve drunkenness.45

Researchers have advanced three principal ways of accounting for the link between alcohol intoxication and violent behavior. The disinhibition theory holds that ingesting alcohol on a pharmacological level impairs normal cortical mechanisms responsible for inhibiting the expression of innate or suppressed aggressive inclina- tions. The cognitive-expectation theory holds that learned beliefs or expectations about alcohol’s effects can facili- tate aggressive behaviors. The implication is that vio- lence is induced by the act of drinking in combination with one’s personal view of how a person is “supposed to respond,” rather than by the pharmacological effects of alcohol itself (Drugs . . . in Focus). The alcohol myo- pia theory holds that intoxicated individuals are limited in their capacity to process information, so that they focus only on the most salient cues in their environment. According to this viewpoint, alcohol reduces the ability to attend to all of the subtle social cues that would have normally led to more appropriate behavior.46

TAble 8.4

Blood-alcohol concentration at which drivers in different nations are legally drunk

0.00+ 0.02 0.03 0.05 0.08

Czech Republic, Norway, Japan, Argentina, Australia, Costa Rica, Brazil, Britain, Canada,

Slovakia, Poland, China Denmark, Finland, France, Italy, Chile, Ecuador, Ireland,

Hungary Sweden Germany, Greece, Netherlands,

Jamaica, New Zealand,

Peru, Russia, South Africa,

Spain, Thailand

Hungary

Singapore,

United States

Source: National Highway Traffic Safety Administration (2000, March). On DWI laws in other countries. Washington DC: National Highway Traffic Safety Administration, U.S. Department of Transportation.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 211

Expectations about the consequences of drug- taking behavior or of any behavior at all, as noted in Chapter 3, are studied experimentally through the placebo research design. Given the prominence of cog- nitive expectations in alcohol research (based on what people know about alcoholic intoxication), it is neces- sary to use a variation of this design, called the balanced placebo design. Subjects are randomly divided into four groups. Two groups are given an alcoholic drink, with one group being told that they are ingesting alco- hol and the other that they are ingesting a nonalcohol substitute that tastes and smells like alcohol. Two other groups are given the nonalcohol substitute, with one group being told that they are ingesting this substitute and the other that they are ingesting alcohol.

Studies using the balanced placebo design have shown clearly that beliefs (mind-sets) concerning the

effects of drinking are more influential in determining a subject’s behavior than the more direct physiological effects of the alcohol. In other words, what they are told they are consuming is more important than what they consume (Health Line). Unfortunately, for a true test of the cognitive-expectation theory, a balanced placebo design cannot be used with BAC levels above 0.035 per- cent, because subjects who drink larger quantities are no longer fooled by the deception, and most alcohol- associated acts of violence occur with BAC levels at least six times higher.47

Drugs . . . in Focus

Alcohol, Security, and Spectator Sports In 2005, the National Basketball Association (NBA) issued a new set of security guidelines for all thirty teams, including a “Fan Code of Conduct” specifying that “guests will enjoy the basketball experience free from disruptive behavior, including foul or abusive language or obscene gestures.” Acknowledging the connection between disruptive behav- ior and alcohol, the NBA now bans alcohol sales during the fourth quarter of every game and imposes a 24-ounce limit on the size of alcoholic drinks sold in an arena, with a maximum of two alcoholic drinks per customer. Increased security measures and restrictions on alcohol sales came about after basketball players and fans brawled in the stands and on the court at the end of a game in November 2004 between the Indiana Pacers and the Detroit Pistons. Indi- ana’s Ron Artest went into the seats after being hit by a full cup of beer that had been tossed by a spectator. Alcohol consumption has also come under scrutiny during college and professional football games, where binge drinking at tailgating parties and after-game celebrations frequently results in property damage and sometimes leads to injuries or deaths. At the University of Virginia, a tradition that began in the 1980s has seniors individually drinking a fifth of liquor by kick-off time at the final game of the football season (the so-called “Fourth-Year Fifth”). This practice

was been associated with the deaths of eighteen students between 1990 and 2002. Since 1999, a university organiza- tion, Fourth-years Acting Responsibly (FAR), has coordi- nated an annual campaign to reduce abusive drinking at the final home game, emphasizing that alcohol intoxication is not needed for intense school spirit. A recent YouTube video features the slogan “Be at your best. Responsible. Respectful. Rowdy.”

At the same time, more than 20 major colleges have initiated beer sales to legal-age drinkers at football games, acknowledging increased revenue that can be realized to athletic programs in their respective institutions. Presently, the National Collegiate Athletic Association (NCAA) does not have any rules preventing alcohol sales at regular-season events, barring sales only during champi- onship games.

Sources: Eskenazi, G. (2005, December 21). For Patriots and Jets, a sobering experience. New York Times, p. D3. Football, tailgating parties, and alcohol safety (2005, October 1). The NCADI Reporter. Bethesda, MD: National Clearinghouse for Drug Information. Join Together (2011, August 8). Beer sales becoming more popular at college football games. New york: The Partnership at DrugFree.org. NBA issuing sterner security, beer guidelines. USA Today. com, accessed May 8, 2005. University of Virginia video (2008, January 31). Be at your best. Responsible. Respectful. Rowdy. University of Virginia, Charlottesville, VA.

balanced placebo design: An experimental design that can distinguish psychological effects (due to sub- jective expectations) from physiological effects (due to the pharmacology of the drug).

212 ■ Part three Legal Drugs in Our Society

Sex and Sexual Desire If they were asked, most people would say that alcohol has an enhancing, or aphrodisiac, effect on sexual desire and performance. The actual effect of alcohol, however, is more complex than what we commonly believe. In fact, it is because of these beliefs that people are fre- quently more susceptible to the expectations of what alcohol should do for them than they are to the actual physiological effects of alcohol.

To examine the complex relationship between alco- hol and sex, we need to turn again to studies using the balanced placebo design. The general results from such studies are quite different for men and women. Among men, those who expected to be receiving low levels of alcohol had greater penile responses, reported greater subjective arousal, and spent more time watching erotic pictures, regardless of whether they did indeed receive alco- hol. When alcohol concentrations rise to levels that reflect genuine intoxication, however, the pharmacological actions outweigh the expectations, and the overall effect is

definitely inhibitory. Men who are drunk have less sexual desire and a decreased capacity to perform sexually.

In contrast, expectations among women play a lesser role. They are more inclined to react to the phar- macological properties of alcohol itself, but the direc- tion of their response depends on whether we are talking about subjective or physiological measures. For women receiving increasing alcohol concentrations, measures of subjective arousal increase but measures of vaginal arousal decrease. The pattern of their responses mirrors Shakespeare’s observation in Macbeth that alcohol “pro- vokes the desire, but it takes away the performance,” a comment originally intended to reflect only the male point of view.48

Alcohol and Health Benefits

The documented health benefits of moderate lev- els of alcohol consumption over the last thirty years of research have presented a major dilemma among

Drugs . . . in Focus

Caffeine, Alcohol, and the Dangers of Caffeinated Alcoholic Drinks Despite the popular notion that caffeine has a “sobering” effect on an alcohol-intoxicated state of mind, the truth is often quite the opposite. It appears to be a factor of one’s expectations. In one study, subjects were told either that caffeine would have a significant “sobering” effect when they were intoxicated with alcohol or that caffeine would have no effect. The participants who were led to expect counteracting effects of alcohol-induced impairments in behavior actually displayed a greater level of impairment than those who were led to expect no such counteraction.

Misconceptions about the effect of caffeine on alcohol- impaired behavior have serious ramifications, particularly in light of the short-lived popularity of caffeinated alco- holic drinks. The malt-liquor-based beverage Four Loko combining caffeine with an alcohol content of between 6 and 12 percent appeared on the scene around 2007. The premise of the public outcry against Four Loko was that the caffeine would mask (but not counteract) the

effects of alcohol, fooling the drinker into thinking that more alcohol could be consumed. In subsequent years, a number of ED-visits among drinkers of caffeinated alco- holic products occurred, and in some cases elevated BAC levels approached the lethal dose range with respect to alcohol toxicity. As noted above, the expectation that the caffeine in a caffeinated alcohol drink would make you less impaired will tend to exacerbate an already dangerous situation. Under intense pressure from the FDA in late 2010, the manufacturers agreed to remove caffeine and other stimulants from the drink. The beverages were rein- troduced in 2011 as a purely alcoholic drink.

Sources: Fillmore, M. T.; Roach, E. L.; and Rice, J. T. (2002). Does caffeine counteract alcohol-induced impairment? The ironic effects of expectancy. Journal of Studies on Alcohol, 63, 745–754. Goodnough, A. (2010, October 27). Doctors point to caffeinated alcoholic drinks’ dangers. New York Times, pp. A12, A14. Tumolillo, M. A. (2010, November 17). Company to drop caffeine from alcoholic drinks. New York Times, p. A22.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 213

medical and public health professionals. The crux of the dilemma is that moderate amounts of alcohol can possibly save your life, while immoderate amounts can possibly destroy it. As one writer has expressed it, “Alco- hol has become the sharpest double-edged sword in medicine.”

It started as an observation that did not seem to make sense. Epidemiological studies of French and other European populations who consumed large amounts of butter, cheese, liver, and other animal fats—a diet associated with elevated cholesterol and an elevated risk for coronary failure—found that these populations had a remarkably low incidence of coronary heart disease. The answer seemed to be that relatively more alcohol was consumed along with their dietary food. The “French paradox” was resolved when later research showed that alcohol increases high-density lipoprotein (HDL) cholesterol (the so- called good cholesterol) levels in the blood, with HDL acting as a protective mechanism against a pos- sible restriction of blood flow through arteries. The greatest benefit was seen in those individuals who had high concentrations of low-density lipoprotein (LDL)

cholesterol (the so-called bad cholesterol) and there- fore had the greatest risk for coronary heart disease. It was estimated that consumption of approximately 8 ounces of wine (a bit less than two standard drinks) per day resulted in a 25 percent reduction in the risk of coronary heart disease.

A natural substance in red wine known as res- veratrol has been identified as a possible factor in explaining the health benefits of drinking red wine. Mice administered resveratrol in very large quanti- ties were higher in endurance levels, relative to con- trols, and were less susceptible to the elevations in glucose and insulin that normally result from eating a high-fat diet. However, these animals received a daily dosage of resveratrol far larger than a human would ingest from drinking wine, so the question of whether this substance is a key factor remains unset- tled. Human intake of resveratrol at comparable dosages would have a significant potential for acute toxicity (Chapter 2).49

Whether these health benefits can be attributed specifically to moderate wine (or red wine) con- sumption or to moderate alcohol consumption in general, remains a controversial issue. The difficulty lies in the fact that wine drinkers tend to have higher socioeconomic status than average alcohol drinkers and typically these people follow healthier lifestyles that reduce the incidence of disease. Yet the evi- dence for moderate alcohol consumption and health benefits is considerable, extending beyond the risk of coronary heart disease. Moderate alcohol intake reduces the risk of diabetes mellitus, reduces the risk of stroke, and reduces the risk of dementia (pos- sibly by reducing the incidence of mini-strokes or by boosting concentrations of vitamin B6, which is essential for the formation of essential brain chemi- cals). Moderate alcohol consumption can also lower the risk of rheumatoid arthritis by up to 50 percent. Of course, the key to the health benefits of alcohol consumption lies in moderation. Moderate drinking has been defined as taking no more than one drink per day for women and no more than two drinks per day for men.50

Despite the weight of evidence tilting toward the potential health benefits of alcohol, the medical field remains divided on the question of whether to encour- age patients who do not drink alcohol to start at a moderate level of consumption. In some cases, mod- erate intake is not advisable. Even one drink per day slightly increases the risk for breast cancer in women,

Quick Concept Check 8.2

Understanding the Data from Balanced Placebo Designs Check your understanding of the balanced placebo design by indicating whether the following experimental results reflect (a) psychological effects, (b) physiological effects, or (c) a combination of psychological and physi- ological effects.

• Scenario 1: Subjects felt sexy after receiving low doses of drug X, regardless of whether they knew what they were receiving.

• Scenario 2: Subjects felt sexy if they received low doses of drug X but were told that they did not receive it and also felt sexy if they did not receive low doses of drug X but were told that they did.

• Scenario 3: Subjects felt sexy after being told they would receive low doses of drug X, regardless of whether they actually received it.

Answers: Scenario 1. b Scenario 2. c Scenario 3. a

214 ■ Part three Legal Drugs in Our Society

and in no circumstances should alcohol be consumed during pregnancy. Some public health researchers are concerned that an endorsement of moderate alco- hol drinking may open up a range of possible risks, in effect giving alcohol a kind of “halo effect” that might be confusing to the public. Besides, an argument can be made that moderate alcohol drinking is simply a behavior that coincides with a healthful lifestyle in the first place, rather than a behavior that actually makes

you healthy. The official word is found in the newest Dietary Guidelines for Americans, released in 2011 by the U.S. Department of Agriculture and the U.S. Department of Health and Human Services, acknowl- edging the effect of alcohol in reducing the risk of cardiovascular disease and helping to keep cognitive function intact with age but not recommending that “anyone begin drinking or drink more frequently on the basis of potential health benefits because moderate

H e A l T H A l e r T !

guidelines for responsible Drinking • Know how much you are drinking. Measure your

drinks. Beer is often premeasured (unless you are drinking draft beer from a keg), but wine and liquor drinks frequently are not. Learn what a 5-ounce quan- tity of wine or a 1½-ounce shot of liquor looks like, and use these measures to guide your drinking.

• Choose beer or wine over liquor. Beer especially will make you feel fuller more quickly, with a smaller intake of alcohol. But be careful. A 12-ounce beer is equivalent in alcohol content to a 5-ounce glass of wine or a 1-shot drink of liquor.

• Drink slowly. One drink an hour stays relatively even with your body’s metabolism of the alcohol you con- sume. Sipping your drinks is a good strategy for slow- ing down your consumption. If you are a man, you’ll look cool; if you are a woman, you’ll look refined.

• Don’t cluster your drinking. If you are going to have seven drinks during a week, don’t drink them all on the weekend.

• Eat something substantial while you are drinking. Protein is an excellent accompaniment to alcohol. Avoid salty foods because they will make you thirstier and more inclined to have another drink.

• Drink only when you are already relaxed. Chronic alcohol abuse occurs more easily when alcohol is viewed as a way to relax. If you have a problem, seek some nondrug alternative.

• When you drink, savor the experience. If you focus on the quality of what you drink rather than the quantity you are drinking, you will avoid drinking too much.

• Never drink alone. Drinking is never an appropriate answer to social isolation. Besides, when there are people around, there is someone to look out for you.

• Beware of unfamiliar drinks. Some drinks, such as zombies and other fruit and rum drinks, are decep- tively high in the kinds of alcohol that are not easily detected by taste.

• Never drive a car after having had a drink. Driving impairment begins after consumption of very low quantities of alcohol.

• Be a good host or hostess. If you are serving alcohol at a party, do not make drinking the focus of activity. Do not refill your guests’ glasses. Discourage intoxication and do not condone drunkenness. Provide transporta- tion options for those who drink at your party. Present nonalcoholic beverages as prominently as alcoholic ones. Prior to the end of the party, stop serving alcohol and offer coffee or other warm nonalcoholic beverages and a substantial snack, providing an interval of non- drinking time before people leave.

• Support organizations that encourage responsible drinking. If you are on a college campus, get involved with the local chapter of BACCHUS (Boost Alcohol Consciousness Concerning the Health of University Students). If there is no chapter, start one.

Sources: Gross, L. (1983). How much is too much? The effects of social drinking. New york: Random House, pp. 149–152. Hanson, D. J., and Engs, R. C. (1994). Drinking behavior: Tak- ing personal responsibility. In P. J. Venturelli (Ed.), Drug use in America: Social, cultural, and political perspectives. Boston: Jones and Bartlett, pp. 175–181. Managing alcohol in your life. Mansfield, MA: Steele Publishing and Consulting.

Where to go for assistance: www.indiana.edu/~engs/hints/holiday.html

This web site on sensible, moderate, and responsible alcohol consumption and party hosting is adapted from Engs, R. C. (1987). Alcohol and other drugs: Self responsibility. Bloomington, IN: Tichenor.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 215

alcohol intake also is associated with increased risk of breast cancer, violence, drowning, and injuries from falls and motor vehicle crashes.”51

Strategies for Responsible Drinking

This chapter has focused on the various negative con- sequences of alcohol consumption on physiological responses and behavior. Yet we need to remember that there are very large numbers of people who drink alcoholic beverages and avoid the adverse effects that have been detailed here. An overwhelming propor- tion of the population, for example, drink on occa- sion, enjoy the experience, and have never engaged

in any violent or aggressive acts. They drink in mod- erate amounts, according to the federal guidelines for diet and nutrition. In addition, they avoid situa- tions (such as driving) in which alcohol consumption would impair their performance and endanger their lives. The issue of responsible drinking is an impor- tant one; it may not be easy for us to accomplish, but fortunately, guidelines exist that make it easier (Health Alert).52

At the same time, it is important to remember that, regardless of how it is consumed, alcohol remains a drug with a significant potential for dependence. It is easy to get hooked. As it has been said, people may plan to get drunk, but no one plans to be an alcoholic. The problems surrounding chronic alcohol abuse and alco- holism are examined in the next chapter.

Summary

What Makes an Alcoholic beverage? ● Drinkable alcohol is obtained from the fermenta-

tion of sugar in some natural products such as grapes, apples, honey, or molasses. The result is some form of wine.

● Beer is obtained from barley, after the starch has first been converted into sugar, fermented along with other grains and hops, and aged.

● To obtain very strong alcoholic beverages, it is neces- sary to boil the fermented liquid and condense it later by cooling. This process, called distillation, results in alcohol concentrations of up to 95 percent, and the products are known as distilled spirits or liquors.

Alcohol use through History ● The history of alcohol use dates back many thousands

of years; the process of fermentation is very simple, and its discovery was probably accidental.

● Distillation techniques were perfected during the Middle Ages, with brandy being the first distilled spirit. In later centuries, gin gained popularity in Europe, as did whiskey in the United States.

● Serious concern about the adverse consequences of alcohol consumption arose in the late 1700s and took root in the United States as a temperance movement. This movement addressed primarily the drinking of distilled spirits.

● The differentiation among forms of alcohol drinking became blurred during the nineteenth century, as

temperance advocates began to promote a total ban on alcohol consumption. National Prohibition was the law in the United States from 1920 to 1933.

● Since the end of Prohibition, government regulation has been carried out chiefly through education and the taxation of alcohol.

Patterns of Alcohol consumption Today ● The demographics of alcohol consumption reveal a

large disparity in the drinking habits of the popula- tion. About a third do not drink at all, and only about 30 percent of those who drink account for 80 percent of all the alcoholic beverages consumed in the United States.

● Peak alcohol consumption occurs at ages twenty-one to twenty-two.

The Pharmacology of Alcohol ● Alcohol is a very small molecule, easily soluble in

both water and fat. Its absorption into the bloodstream is extremely rapid. The breakdown of alcohol is han- dled by two special enzymes in the stomach and liver.

● The rate of alcohol biodegradation is constant, so alcohol can leave the body only at a specific pace, no matter what the quantity taken in.

● The effective level of alcohol in the body is measured by the blood-alcohol concentration (BAC) level, which adjusts for differences in body weight and the time since ingestion of the last alcoholic beverage.

216 ■ Part three Legal Drugs in Our Society

effects of Alcohol on the brain ● Although alcohol affects several neurotransmitters in

the brain, it is presently agreed that the principal ef- fect is stimulation of the GABA receptor.

● Generally, the neural effect of alcohol proceeds down- ward, beginning with inhibition of the cerebral cortex, then that of lower brain regions. Inhibition of respira- tory systems in the medulla, usually accomplished at BAC levels in the neighborhood of 0.50 percent, re- sults in asphyxiation and death.

Acute Physiological effects ● Alcohol at very high levels produces life-threatening

consequences and at moderate levels produces a loss of body heat, increased excretion of water, an increase in heart rate and constriction of coronary arteries, dis- turbed patterns of sleep, and serious interactions with other drugs.

Acute behavioral effects ● On a behavioral level, serious adverse effects include

blackouts, significant impairment in sensorimotor skills such as driving an automobile, and an increased potential for aggressive or violent acts. Particular

attention has been directed toward these problems within a college student population.

● The relationship between alcohol consumption and sexual desire and performance is a complex one, with differences being observed for men and women.

Alcohol and Health benefits ● The accumulated evidence of medical research has

indicated that there is a reduced risk for coronary heart disease and stroke with moderate consumption of alcohol. Possible health benefits include a reduc- tion of risk for diabetes, dementia, and rheumatoid arthritis.

● Moderate alcohol consumption has been defined as no more than one drink per day for women and no more than two drinks per day for men. There should be zero tolerance for alcohol consumption among pregnant women.

Strategies for responsible Drinking ● Despite the potential for alcohol consumption to pro-

duce adverse effects, most people can drink alcohol in a responsible way that avoids these harmful conse- quences. However, the risk of alcohol dependence is always present.

Key terms

acetaldehyde, p. 202 acetaldehyde

dehydrogenase, p. 202 acetic acid, p. 202 alcohol dehydrogenase,

p. 202 antidiuresis, p. 206

antidiuretic hormone (ADH), p. 206

aqua vitae, p. 194 balanced placebo design,

p. 211 barley malt, p. 192 blackout, p. 208

blood-alcohol concentration (BAC), p. 203

brewing, p. 192 congeners, p. 207 distillation, p. 193 distilled spirits, p. 193 ethyl alcohol, p. 192

fermentation, p. 192 mash, p. 192 oxidation, p. 202 temperance

movement, p. 195

endnotes

1. Pinel, J. P. J. (2011). Biopsychology (8th ed.). Boston: Allyn and Bacon, p. 384.

2. Statement of NIH Director Dr. Francis Collins on the future of substance use, abuse, and addiction-related research at NIH. News release, National Institutes of Health. Bethesda, MD, November 1i6, 2012.

3. Gibbons, B. (1992, February). Alcohol: The legal drug. National Geographic Magazine, pp. 2–35. McGovern, P. E.; Glusker, D. L.; Exner, L. J.; and Voigt, M. M. (1996). Neolithic resinated wine. Nature, 381, 480–481. Roueché, B. (1963). Alcohol in human culture. In S. P. Lucia (Ed.), Alcohol and civilization. New York: McGraw-Hill, pp. 167–182. Vallee, B. L. (1998, June).

Alcohol in the western world. Scientific American, pp. 80–85.

4. Sournia, J. C. (1990). A history of alcoholism. Cambridge, MA: Basil Blackwell, pp. 14–50. U.S. Department of Health, Education, and Welfare (1978). Perspectives on the history of psychoactive substance use, pp. 67–75.

5. Grimes, W. (1993). Straight up or on the rocks: A cultural history of American drink. New York: Simon and Schuster, p. 36. Musto, D. F. (1996, April). Alcohol in American history. Scientific American, pp. 78–83.

6. Lender, M. E., and Martin, J. K. (1982). Drinking in America: A history. New York: Free Press, pp. 13–14.

Chapter 8 Alcohol: Social Beverage/Social Drug ■ 217

7. First in war, peace—and hooch, by George! (2000, December 7). Newsday, p. A86. Grimes, Straight up, p. 51.

8. Quoted in Sournia, J. C. (1990). A history of alcoholism. Cambridge, MA: Basil Blackwell, p. 29.

9. Lincoln, A. (1842/1989). Address to the Washingtonian Temperance Society of Springfield, Illinois. Speeches and writings, 1832–1858. New York: Library of America, p. 84.

10. Lender, M. E., and Martin, J. R. (1982). Drinking in America: A history. New York: Free Press, p. 107. Okrent, D. (2010). Last call: The rise and fall of Prohibi- tion. New York: Scribner.

11. Blocker, J. S. (2006, February). Did Prohibition really work? Alcohol prohibition as a public health innovation. American Journal of Public Health, pp. 233–243. Lerner, M. A. (2007). Dry Manhattan. Cambridge, MA: Harvard University Press. Musto, D. F. (1996, April). Alcohol in American history. Scientific American, pp. 78–83. Sournia, History of alcoholism, p. 122.

12. Americans for Tax Reform Center for Fiscal Accountabil- ity, Washington, DC, 2012. U.S. Department of Health and Human Services (2000). Alcohol and health (Tenth Special Report to the U.S. Congress). Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism, p. 370. Industry Surveys (1997, September 11). Alcoholic beverages and tobacco, p. 16.

13. Gruenewald, P. J. (2011). Regulating availability: How access to alcohol affects drinking and problems of youth and adults. Alcohol Research and Health, 34, 248–256. Xu, X., and Chaloupka, F. J. (2011). The effects of prices on alcohol use and its consequences. Alcohol Research and Health, 34, 236–245.

14. Gibbons, Alcohol, p. 7. 15. Alcohol Policies Project, Center for Science in the Pub-

lic Interest Fact Sheet, Washington, DC, 2012. Hanson, G. R., and Li, T. K. (2003). Public health implications of excessive alcohol consumption. Journal of the American Medical Association, 289, 1031–1032. National Associa- tion of Convenience Stores (2008). That’s the spirit— U.S. alcohol sales growing. www.nacsonline.com.

16. Statistics on 2009 consumption levels from the National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD.

17. Center for Science in the Public Interest (2008, August 8). Press release: CSPI blasts NCAA decision to keep beer ad. Center for Science in the Public Interest, Wash- ington, DC. Rogers, J. D., and Greenfield, T. K. (1999). Beer drinking accounts for most of the hazardous alcohol consumption reported in the United States. Journal of Studies on Alcohol, 60, 732–739.

18. Centers for Disease Control and Prevention (2012, January 13). Vital signs: Binge drinking prevalence, frequency, and intensity among adults—United States, 2010. Morbidity and Mortality Weekly, 61, 14–19. Hingson, R. W.; Zha, W.; and Weitzman, E. R. (2009). Magnitude of and trends in alcohol-related mortality

and morbidity among U.S. college students ages 18–24, 1998–2005. Journal of Studies on Alcohol and Drugs, Supplement No. 16, 12–20. National Institute on Alcohol and Alcohol Abuse (2007). What colleges need to know now: An update on college drinking research. Bethesda, MD: National Institute on Alcohol and Alcohol Abuse. National Institute on Alcohol and Alcohol Abuse (2010). Statistical snapshot of college drinking. Bethesda, MD: National Institute on Alcohol and Alcohol Abuse. Wechsler, H., and Nelson, T. F. (2008). What we have learned from the Harvard School of Public Health College Alcohol Study: Focusing attention on college student alcohol consumption and the environmental conditions that promote it. Journal of Studies on Alcohol and Drugs, 69, 1–10. ; Wechsler, H.; Lee, J. E.; Kuo, M.; Seibring, M.; Nelson, T. F.; et al. (2002). Trends in college binge drinking during a period of increased prevention efforts: Findings from four Harvard School of Public Health College Alcohol Study Surveys: 1993– 2001. Journal of American College Health, 50, 203–217.

19. Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2012). Monitoring the Future: National survey results on drug use, 1975–2011. Vol. I: Secondary school students 2011. Ann Arbor, MI: Insti- tute for Social Research, The University of Michigan, Table 2-1. Substance Abuse and Mental Health Services Administration (2008, August 28). Underage alcohol use: Where do young people drink? The NSDUH Report. Rockville, MD: Substance Abuse and Mental Health Services Administration. Windle, M., and Zucker, R. A. (2010). Reducing underage and young adult drinking: How to address critical drinking problems during this developmental period. Alcohol Research and Health, 33, 29–44.

20. U.S. Department of Health and Human Services (1990). Alcohol and health. (The Seventh Special Report to the U.S. Congress). Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism.

21. Julien, R. M. (2005), A primer of drug action (10th ed.). New York: Worth, pp. 91–126.

22. Julien, R. M. (2000). A primer of drug action (9th ed.). New York: Worth, p. 95.

23. National Institute on Alcohol Abuse and Alcoholism (2007, April). Alcohol alert: Alcohol metabolism: An update. No. 72. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism. Julien, A primer of drug action, pp. 91–97.

24. Suter, P. M.; Schutz, Y.; and Jequier, E. (1992). The effect of ethanol on fat storage in healthy subjects. New England Journal of Medicine, 326, 983–987.

25. Hawks, R. L., and Chiang, C. N. (1986). Examples of specific drug assays. In R. L. Hawks and C. N. Chiang (Eds.), Urine testing for drugs of abuse (NIDA Research Monograph 73). Rockville, MD: National Institute on Drug Abuse, p. 103. Julien (2000), A primer of drug action, pp. 91–97.

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26. Levinthal, C. F. (1990). Introduction to physiological psy- chology (3rd ed.). Englewood Cliffs, NJ, Prentice-Hall, pp. 181–184.

27. U.S. Department of Health and Human Services (1994). Alcohol and health. (The Eighth Special Report to the U.S. Congress). Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism, pp. 4–6, 4–7.

28. Koob, G. F.; Rassnick, S.; Heinrichs, S.; and Weiss, F. (1994). Alcohol, the reward system and dependence. In B. Jansson, H. Jörnvall, U. Rydberg, L. Terenius, and B. L. Vallee (Eds.), Toward a molecular basis of alcohol use and abuse. Basel: Birkhäuser-Verlag, pp. 103–114. Rosenbloom, M. J., and Pfefferbaum, A. (2008). Mag- netic resonance imaging of the living brain. Evidence for brain degeneration among alcoholics and recovery with abstinence. Alcohol Research and Health, 31, 362–376.

29. Grilly, D. M., and Salamone, J. D. (2012). Drugs and human behavior (6th ed.). Boston: Pearson, p. 238.

30. Luks, A., and Barbato, J. (1989). You are what you drink. New York: Villiard, pp. 42–43.

31. National Institute on Alcohol Abuse and Alcoholism (1998, July). Alcohol alert: Alcohol and sleep. No. 41. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism.

32. O’Connor, M. J., and Wahley, S. E. (2007). Brief inter- vention for alcohol use by pregnant women. American Journal of Public Health, 97, 252–258. Substance Abuse and Mental Health Services Administration (2012). Drug Abuse Warning Network, National estimates of drug- related emergency department visits 2004–2010. Rock- ville, MD: Substance Abuse and Mental Health Services Administration, Excel files. Substance Abuse and Mental Health Services Administration (2012). Results from the 2011 National Survey on Drug Use and Health: National findings. Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Administration, Table 6-76B.

33. Schuckit, M. A. (2006). Drug and alcohol abuse: A clini- cal guide to diagnosis and treatment (6th ed.). New York: Springer, p. 88.

34. Wiese, J. G.; Shlipak, M. G.; and Browner, W. S. (2000). The alcohol hangover. Annals of Internal Medicine, 232, 897–902.

35. Brick, J. (2008). Characteristics of alcohol: Definitions, chemistry, measurement, use, and abuse. In J. Brick (Ed.), Handbook of the medical consequences of alcohol and drug abuse (2nd ed.). New York: Routledge, pp. 9–19.

36. White, A. M.; Jamieson-Drake, D. W.; and Swartzwelder, H. S. (2002). Prevalence and correlates of alcohol- induced blackouts among college students: Results of an e-mail survey. Journal of American College Health, 51, 117–131. White, A. M. (2003). What happened? Alcohol, memory blackouts, and the brain. Alcohol Research and Health, 23, 186–196.

37. National Highway Traffic Safety Administration (2012, December). 2011 motor vehicle crashes: Overview. Traffic Safety Facts: Research Note, p. 2.

38. Hoyer, W. J.; Semenec, S. C.; and Buchler, N. E. G. (2007). Acute alcohol intoxication impairs controlled search across the visual field. Journal of Studies on Alcohol and Drugs, 68, 748–758. National Institute on Alcohol Abuse and Alcoholism (1996, January). Alcohol Alert: Drinking and driving. No. 31, PH362. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism.

39. Gross, L. (1983). How much is too much? The effects of social drinking. New York: Random House, p. 29. Quotation of Dr. H. Moskowitz.

40. National Institute on Alcohol Abuse and Alcoholism (2001, April). Alcohol alert: Alcohol and transportation safety. No. 52. Bethesda, MD: National Institute on Alco- hol Abuse and Alcoholism. Wagenaar, A. C.; O’Malley, P. M.; and LaFond, C. (2001). Lowered legal blood alcohol limits for young drivers: Effects on drinking, driving, and driving-after-drinking behaviors in 30 states. American Journal of Public Health, 91, 801–803.

41. Substance Abuse and Mental Health Services Administra- tion (2012, November). Report to Congress on the preven- tion and reduction of underage drinking. Rockville, MD: Substance Abuse and Mental Health Services Adminis- tration. National Highway Traffic Safety Administration (2009, June). Lives saved in 2008 by restraint use and minimum drinking age laws. Traffic Safety Facts. Washington, DC: National Center for Statistics and Analysis, National Highway Traffic Safety Administration. Wald, M. L. (2006, November 20). A new strategy to discourage driving drunk. New York Times, pp. A1, A20.

42. National Conference of State Legislatures (2012). State ignition interlock laws. National Conference of State Legislatures, Washington, DC.

43. Hingson, R.; Heeren, T.; Zakocs, R.; Winter, M.; and Wechsler, H. (2003). Age of first intoxication, heavy drinking, driving after drinking and risk of unintentional injury among U.S. college students. Journal of Studies on Alcohol, 64, 23–31. National Highway Traffic Safety Ad- ministration (2010, August). National survey of drinking and driving attitudes and behaviors. Washington, DC: U.S. Department of Transportation. National Highway Traffic Administration (1999, March). The relationship of alcohol safety laws to drinking drivers in fatal crashes. Washington, DC: U.S. Department of Transportation. Substance Abuse and Mental Health Services Adminis- tration, Results from the 2011 National Survey on Drug Use and Health: Detailed tables.

44. Abbey, A.; Zawacki, T.; Buck, P. O.; Clinton, A. M.; and McAuslan, P. (2004). Sexual assault and alcohol consumption: What do we know about their relationship and what types of research are still needed? Aggression and Violent Behavior, 9, 271–303. Haggård-Grann, U.; Hallqvist, J.; Långström, N.; and Möller, J. (2006). The role of alcohol and drugs in triggering criminal violence: A case-crossover study. Addiction, 101, 100–108. Per- nanen, K. (1991). Alcohol in human violence. New York: Guilford Press, pp. 192–193.

Chapter 8 alcohol: Social Beverage/Social Drug ■ 219

45. Collins, J. J., and Messerschmidt, P. M. (1993). Epide- miology of alcohol-related violence. Alcohol Health and Research World, 17, 93–100. Goode, E. (2008). Drugs in American society (7th ed.). New York: McGraw-Hill, pp. 343–346. National Institute on Alcohol Abuse and Alcoholism (1997, October). Alcohol alert: Alcohol, vio- lence, and aggression. No. 38. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism.

46. Giancola, P. R. (2000). Executive functioning: A con- ceptual framework for alcohol-related aggression. Experi- mental and Clinical Psychopharmacology, 8, 576–597. Giancola, P. R. (2002). Alcohol-related aggression in men and women: The influence of dispositional aggres- sivity. Journal of Studies on Alcohol, 63, 696–708. Grant, N. K., and MacDonald, T. K. (2005). Can alcohol lead to inhibition or disinhibition? Applying alcohol myopia to animal experimentation. Alcohol and Alcoholism, 40, 2005. Norris, J.; David, K. C.; George, W. H.; Martell, J.; and Heiman, J. R. (2002). Alcohol’s direct and indirect effects on men’s self-reported sexual aggression likeli- hood. Journal of Studies on Alcohol, 63, 688–695.

47. Foran, H. M., and O’Leary, K. D. (2008). Alcohol and intimate partner violence: A meta-analytic review. Clinical Psychology Review, 28, 1222–1234. Pernanen, K. (1993). Research approaches in the study of alcohol-related vio- lence. Alcohol Health and Research World, 17, 101–107.

48. Cooper, M. L. (2006). Does drinking promote risky sexual behavior? A complex answer to a simple ques- tion. Current Directions in Psychological Science, 15, 19–23. Enyeart Smith, T. M., and Wessel, M. T. (2011). Alcohol, drugs, and links to sexual risk behaviors among a sample of Virginia college students. Journal of Drug Education, 41, 1–16. Testa, M.; Vanzile-Tamsen, C.; and Livingston, J. A. (2004). The role of victim and perpetra- tor intoxication on sexual assault outcomes. Journal of Studies on Alcohol, 65, 320–329.

49. Mochly-Rosen, D., and Zakhari, S. (2010). The cardio- vascular system: What did we learn from the French (par- adox)? Alcohol Research and Health, 33, 76–86. Rimm, E. B. (2000). Moderate alcohol intake and lower risk of coronary heart disease: Meta-analysis of effects on lipids and haemostatic factors. Journal of the American Medical

Association, 283, 1269. Wade, N. (2006, November 2). Yes, red wine holds answer. Check dosage. Zuger, A. (2002, December 31). The case for drinking (all together now: in moderation). New York Times, pp. F1, F6. Quotation on p. F1.

50. Holahan, C. J.; Schutte, K. K.; Brennan, P. L.; North, R. J., Holahan, C. K., et al. (2012). Wine consumption and 20-year mortality among late-life moderate drink- ers. Journal of Studies of Alcohol and Drugs, 73, 80–88. Howard, A. A.; Arnsten, J. H.; and Gourevitch, M. N. (2004). Effect of alcohol consumption on diabetes mel- litus: A systematic review. Annals of Internal Medicine, 140, 211–219. Källberg, H.; Jacobsen, S.; Bengtsson, C.; Pdersen, M.; Padyukov, L.; et al. (2009). Alcohol con- sumption is associated with decreased risk of rheumatoid arthritis: Results from two Scandinavian case-control studies. Annals of the Rheumatic Diseases. 68, 222–227. Mukamal, K. J.; Conigrave, K. M.; Mittleman, M. A.; Carmargo, C. A., Jr.; Stampfer, M. J.; et al. (2003). Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men. New England Journal of Medicine, 348, 109–118. Mukamal, K. J.; Kuller, L. H.; Longstreth, W. T.; Mittleman, M. A.; and Siscovick, D. S. (2003). Prospective study of alcohol consump- tion and risk of dementia in older adults. Journal of the American Medical Association, 289, 1405–1413. Reynold, K.; Lewis, L. B.; Nolen, J. D. L.; Kinney, G. L.; Sathya, B.; et al. (2003). Alcohol consumption and risk of stroke: A meta-analysis. Journal of the American Medical Associa- tion, 289, 579–588.

51. Goldberg, I. (2003). To drink or not to drink? New England Journal of Medicine, 348, 163–164. Klatsky, A. (2003, February). Drink to your health? Scientific American, pp. 75–81. Rabin, R. C. (2009, June 19). Alcohol’s good for you? Some scientists doubt it. New York Times, pp. D1, D6. U.S. Department of Agriculture and U.S. Department of Health and Human Services (2010). Dietary guidelines for Americans, 2010 (7th ed.). Washington DC: U.S. Government Printing Office, p. 31.

52. Darby, W., and Heinz, A. (1991). The responsible use of alcohol: Defining the parameters of moderation. New York: American Council on Science and Health, pp. 1–26.

220

C h a p t e r

9 Chronic Alcohol Abuse and AlcoholismAfter you have completed this chapter, you should

have an understanding of

▶ Problems surrounding the definition of alcoholism

▶ Physiological effects of chronic alcohol abuse

▶ Patterns of chronic alcohol abuse

▶ Special problems among the elderly

▶ Family dynamics in alcoholism

▶ Genetic and environmental influences in alcoholism

▶ Approaches to treatment for alcoholism

▶ Chronic alcohol abuse and alcoholism in the workplace

When you live in an alcoholic family, you lie in bed some-

times and imagine how things could be different. You

dream that you could actually invite your friends over to

hang out at your house. You dream that the family car

wouldn’t get its fenders bashed in on a regular basis. You

dream that the money you made mowing lawns didn’t end

up missing from your room. You dream that someone had

been there at the athletic awards banquet. You dream

that you didn’t have to plead with them to quit drinking—

time after time. You dream that enlisting in the military isn’t

just a way of getting out of the house. You dream that your

life is normal, except that you have no idea what normal is.

—Thoughts of a teenager in an alcoholic family

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 221

For chronic abusers of alcohol, there is no need to get out on the street and find a drug dealer. Alcohol con- sumption is so tightly woven into the social fabric of our lives that it is easy to drink too much too often. Currently, an estimated 18.2 million Americans have a serious long- term problem with alcohol. Considering that for each one of these individuals, it is estimated that four family members are directly affected, the consequences extend to approximately 80 million people in the United States. This chapter will continue the examination of the impact of alcohol in America and specifically deal with the very serious problems associated with chronic alcohol abuse.1

Alcoholism: Stereotypes, Definitions, and Life Problems

If you were asked to imagine what an alcoholic looks like, it is likely that you would not form an image of a person employed in a highly responsible position or a teenager. You might be thinking of someone, probably male, homeless and alone, living from day to day in a continual state of inebriation and deteriorating health. Chances are that the characteristics of the person who came to mind would match up with fewer than 5 percent of all alco- holics. It turns out that the demographics of alcoholism include every possible category. Alcoholics can be four- teen or eighty-four years of age, male or female, profes- sional or blue-collar, employed or unemployed. They can be urbanites, suburbanites, or rural residents in any com- munity. Typically, they have jobs, a home, and a family.

What aspects of their behavior tie them all together, allowing us to describe their condition with a single

label? In order to arrive at a general sense of what we mean by an individual being an alcoholic, we need to examine the signs, symptoms, and behaviors that consti- tute problematic drinking. However, health profession- als have abandoned the specific term, alcoholism, as a diagnosis in favor of criterion-based diagnoses, such as alcohol abuse and alcohol dependence or alcohol use disorder (see pages 225–226).

Four basic life problems are tied to the con- sumption of alcohol: (1) problems associated with a preoccupation with drinking, (2) emotional prob- lems, (3) vocational, social, and family problems, and (4) problems associated with physical health. In short, we are recognizing that alcoholism is a complex phe- nomenon with psychological-behavioral components (problems 1 and 2), social components (problem 3), and physical components (problem 4).

Problems Associated with a Preoccupation with Drinking The dominant characteristic of alcoholics is their preoc- cupation with the act of drinking and their incorporation of drinking into their everyday lives. An alcoholic may need a drink prior to a social occasion to feel “fortified.” With increasing frequency, such a person sees alcohol as a way of dealing with stress and anxiety. Drinking itself becomes routine, no longer a social affair. The habit of taking a few drinks upon arriving home from work each day is an example of symptomatic drinking, in which alcohol is viewed specifically as a way of relieving ten- sion, depression, or some other negative mood state. Also increasing is the incidence of unintentional occasions of severe intoxication and blackouts of events surrounding the time of drinking, a condition quite different from “passing out” from a high BAC level (see Chapter 8).2

Traditionally, alcoholism is associated with con- sumption of a large quantity of alcohol. This sounds pretty obvious and is true of most alcoholics, but not all alcoholics consume alcohol in the same way. Not all of them begin every day with a drink. Many of them drink on a daily basis, but others are spree or binge alcoholics who might become grossly intoxicated at intervals dur- ing a given week and totally abstain from drinking the rest of the time. Given these differences in the pattern of

by the numbers . . .

6.3 Estimated percentage of U.S. college students (one in sixteen) who meet the criteria for alcohol dependence.

2.1 million Estimated number of Americans who report that they have worked under the influence of alcohol in the past twelve months, from a national sample of employed adults

Sources: Frone, M. R. (2006). Prevalence and distribu- tion of alcohol use and impairment in the workplace: A U.S. survey. Journal of Studies on Alcohol and Drugs, 67, 147–156. Knight, J. R.; Wechsler, H.; Kuo, M.; Seibring, M.; Weitzman, E. R.; and Schuckit, M. A. (2002). Alcohol abuse and dependence among U.S. college students. Journal of Studies on Alcohol, 63, 263-270.

alcoholism: A condition in which the consumption of alcohol has produced major psychological, physical, social, or occupational problems.

symptomatic drinking: A pattern of alcohol consumption aimed at reducing stress and anxiety.

222 ■ Part Three Legal Drugs in Our Society

This poster conveys a powerful message: Alcoholism affects such a diverse group of people that it is virtually impossible to make generalizations about the typical profile of an alcoholic. Here are sixteen examples of indi- viduals with whom many people might not have immediately associated the term “alcoholic.”

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 223

alcohol consumption, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has recently established guidelines for “at-risk” or “heavy” drinking based on both a single-day level and a weekly level of consumption. Just as binge drinking was defined separately for men and women (Chapter 8), there are two different thresholds for being in the “at-risk” or “heavy” drinking category, depending on gender. These thresholds are:

■ More than four drinks on any day and more than 14 drinks per week (for men).

■ More than three drinks on any day and more than seven drinks per week (for women).

Individuals drinking more than both the single-day and weekly limits (about nine percent of the adult U.S. population) carry the highest risk for alcoholism-related problems; individuals drinking more than either the single-day or weekly limits (about 19 percent) carry an increased risk.3

Another feature often attributed to alcoholics is a loss of control over their drinking. The alcoholic typi- cally craves a drink and frequently engages in compul- sive behavior related to alcohol, much in the same way as we have seen in stimulant dependence (Chapter 4) or opioid dependence (Chapter 5), except that in the case of alcoholism, the behavior is often embedded in a social context. There may be a stockpiling of liquor, taking a drink or two before going to a party, or feeling uncomfortable unless alcohol is present. The alcoholic may be sneaking drinks or having drinks that others do not know about, such as surreptitiously having an extra drink or two in the kitchen out of the sight of the party guests.4 Particularly when the alcoholic is trying to abstain from alcohol or to reduce the quantity of alco- hol consumed, his or her thoughts become focused on the possibility of drinking or on ways to rationalize it.5

Nonetheless, health professionals disagree about whether all alcoholics are necessarily out of control with respect to alcohol consumption. As discussed later in the chapter, this controversy has major implications for choosing the treatment approach in cases of alcohol abuse. If it is true that even a small amount of alcohol will propel a recovering alcoholic back to alcohol abuse, then a primary focus of treatment should be on “no drinking at all”—better known as absolute abstinence. If it is not true, then there is the possibility of controlled drinking without the fear of “falling off the wagon.” The well-known alcohol treatment program Alcoholics Anonymous, for example, functions under the assump- tion that an alcoholic must never drink again, even in minute quantities, if recovery is to be sustained over a long period of time.

Emotional Problems Given that alcohol is a depressant drug on the central nervous system, it should not be surprising that chronic alcohol intake produces depressive symptoms. Serious depressions and thoughts of suicide frequently occur in the midst of heavy drinking. It is estimated that about 40 percent of individuals who meet the criteria for alco- hol dependence (see page 225) will have one or more alcohol-induced depressive episodes. Nonetheless, the frequency of severe depressions lasting every day for weeks on end and observed outside of the context of heavy drinking may be no more prevalent in alcoholics than in the general population.6

Vocational, Social, and Family Problems No one questions the potential problems that chronic alcohol abuse can bring to the maintenance of a job or career, social relationships, and a stable family life. These three problem areas frequently intertwine, with trouble in one usually exacerbating trouble in another. A job loss puts stress on marital and family relationships, just as marital and family difficulties put stress on occu- pational performance.

Numerous clinical studies support the idea of increased domestic instability in the lives of alcoholics, but the true extent of these problems is difficult to assess. Family violence, for example, is frequently examined through cases seen in treatment or social service programs. As a result, these agencies may interpret the domestic behavior of a father not known to have a drinking problem differently from that of a father with a history of alcohol- ism. A man who drinks heavily and abuses his children may be more likely to be “counted” as an alcoholic than a nonabusive father who consumes just as much alcohol. It is much easier to assess the likelihood of domestic vio- lence or decline in job performance due to acute intoxica- tion than it is to evaluate the influence of chronic abuse of alcohol. Even so, there is no doubt that the cumulative effects of alcoholism on family dynamics are devastating.7

Physical Problems There is also no question that chronic alcohol consump- tion has a destructive effect on the body. Not surprisingly, a principal site of damage is the brain. Neuroimaging

abstinence: The avoidance of some consumable item or behavior.

224 ■ Part Three Legal Drugs in Our Society

procedures, such as CT and MRI brain scans, reveal a consistent link between heavy drinking and physical shrinkage of brain matter, particularly in the cerebral cor- tex, cerebellum, and regions associated with memory and other cognitive functions. These neurological changes are observed even in the absence of other alcohol-related medical conditions such as chronic liver disease.8

Hiding the Problems: Denial and Enabling The major life problems that serve as rough criteria for determining the condition of alcoholism are often not recognized by alcoholics themselves because of their ten- dency to deny that their drinking has any influence on their lives or the lives of people around them. When in denial, the alcoholic can be extremely sensitive to any mention

of problems associated with drinking. A hangover the next day, for example, is seldom discussed because it would draw attention to the fact that drinking has occurred.9

Denial also can be manifest among the people around the alcoholic. Members of an alcoholic’s fam- ily, for example, may try to function as if life were nor- mal. Through their excuse making and efforts to undo or cover up the frequent physical and psychological damage the alcoholic causes, they inadvertently prevent the alco- holic from seeking treatment or delay that treatment until the alcoholism is more severe. These people are referred to as enablers because they enable the alcoholic to func- tion as an alcoholic rather than as a sober person. Both processes of denial and enabling present major difficul- ties not only in establishing problem-oriented criteria for diagnosing alcoholism but also in introducing necessary interventions. Denial and enabling are clearly relevant processes in the area of alcoholism, but it is not difficult to see that they present problems with regard to treatment for any form of substance abuse (see Chapter 17).

Health Line provides a useful self-survey for identi- fying signs of potential alcoholism.

Health Line A Self-Administered Short Michigan Alcoholism Screening Test (SMAST)

The Michigan Alcoholism Screening Test (MAST), twenty- four questions to be answered in ten to fifteen minutes, is designed as a structured interview instrument to detect alco- holism. A shorter, thirteen-question version (SMAST-13), shown here, has approximately the same level of reliability and validity. Score one point for each response that matches the one in parentheses. According to the authors of the test, a total score of 0 or 1 indicates a nonalcoholic, 2 a possible alcoholic, and 3 or more an alcoholic.

1. Do you feel you are a normal drinker? (By normal we mean you drink less than or as much as most other people.) (NO)

2. Does your wife, husband, a parent, or other near rela- tive ever worry or complain about your drinking? (YES)

3. Do you ever feel guilty about your drinking? (YES) 4. Do friends or relatives think you are a normal

drinker? (NO) 5. Are you able to stop drinking when you want to? (NO) 6. Have you ever attended a meeting of Alcoholics

Anonymous? (YES) 7. Has drinking ever created problems between you and

your wife, husband, a parent, or other near relative? (YES)

8. Have you ever gotten into trouble at work because of drinking? (YES)

9. Have you ever neglected your obligations, your fam- ily, or your work for two or more days in a row be- cause you were drinking? (YES)

10. Have you ever gone to anyone for help about your drinking? (YES)

11. Have you ever been in a hospital because of drink- ing? (YES)

12. Have you ever been arrested for drunken driving, driving while intoxicated, or driving under the influ- ence of alcoholic beverages? (YES)

13. Have you ever been arrested, even for a few hours, because of other drunken behavior? (YES)

Sources: Barry, K. L., and Fleming, M. F. (1993). The Alcohol Use Disorders Identification Test (AUDIT) and the SMAST-13: Predictive validity in a rural primary care sample. Alcohol and Alcoholism, 28, 33–42. Selzer, M. L.; Vinokur, A.; and van Rooijen, L. (1975). A self-administered Short Michigan Alcoholism Screening Test (SMAST). Journal of Studies on Alcohol, 36, 117–126.

enablers: Individuals whose behavior consciously or unconsciously encourages another person’s continuation in a pattern of alcohol or other drug abuse.

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 225

Alcohol Abuse and Alcohol Dependence: The Health Professional’s Perspective

As you can see, the problem areas commonly employed in determining the presence of alcoholism are at times quite murky, and often there are nearly as many coun- terexamples as there are examples. The American Psychiatric Association, through its Diagnostic and Statistical Manual, Text Revision, fourth edition (DSM- IV-TR), has attempted to put together as many common features as possible and has established two basic syn- dromes. It is important to understand these technical definitions, because professionals in the field of alco- holism commonly use the DSM-IV-TR either in their research or in clinical practice.10

The first syndrome, referred to as alcohol abuse, is characterized as either (1) the continued use of alcohol for at least one month despite the knowledge of having a persistent or recurring physical problem or some dif- ficulty in social or occupational functioning, or (2) the recurring use of alcohol in situations (such as driving) when alcohol consumption is physically hazardous.

The second syndrome, referred to as alcohol dependence, is characterized as alcohol abuse that involves any three of the following seven circumstances:

■ Consuming alcohol in greater amounts or over a longer period than the person intends

■ A persistent desire, or one or more unsuccessful attempts, to cut down or control drinking

■ A great deal of time spent drinking or recovering from the effects of drinking

■ Alcohol consumption continuing despite knowledge that drinking either causes or exacerbates recurrent physical or psychological problems

■ Major social, occupational, or recreational activities given up or reduced because of alcohol

■ Marked tolerance or the need to drink more than before to achieve previous levels of intoxication

■ Symptoms of alcohol withdrawal or the consumption of alcohol to relieve or avoid withdrawal symptoms

Obviously, individuals who fit the second definition are considered more greatly impaired than those who fit the first. That distinction also was true with regard to the more general criteria for substance abuse and sub- stance dependence (see Chapter 2). At least 15 percent of men and about 10 percent of women in the U.S. have met the criteria for alcohol dependence at some time in their lives. An estimated 10 percent of adults overall and 6 percent of college students have met the criteria for alcohol dependence during the past year.11

As noted in Chapter 2, the new DSM-5 revision in 2013 combines the diagnoses of alcohol abuse and alco- hol dependence into one diagnosis: alcohol use disorder. Like the more general diagnosis of substance use disorder, the new diagnosis of alcohol use disorder is made on the basis of the same behavioral criteria previously identified

Quick Concept Check 9.1

Understanding the Psychology of Alcoholism Check your understanding of the psychological aspects of alcoholism by matching each quotation or behavioral description (on the left) with the appropriate term (on the right).

1. Brad tries to call his estranged wife on the telephone. She hangs up on him. Now angry and frustrated, Brad takes a drink.

2. Mary stays sober during the workweek, but on the weekend she downs at least two quarts of vodka.

3. “Despite what my family says, I am convinced I am not an alcoholic.”

4. “If I’m with her when she’s drink- ing, I can make sure she doesn’t overdo her drinking.”

5. “I’m going to the theater later. I don’t think there will be any liquor there, so I had better have a couple of drinks before I go.”

a. denial

b. enabling

c. out-of-control drinking

d. spree or binge drinking

e. symptomatic drinking

Answers: 1. e 2. d 3. a 4. b 5. c

alcohol abuse: A syndrome characterized primarily by the continued use of alcohol despite the drinker’s knowledge of having a persistent physical problem or some social or occupational difficulty.

alcohol dependence: A syndrome in which alcohol abuse involves a variety of significant physical, psychological, social, and behavioral problems.

226 ■ Part Three Legal Drugs in Our Society

with alcohol abuse and alcohol dependence, with the exception that the criterion of “legal problems” has been dropped and the criterion of “craving” has been added.12

Physiological Effects of Chronic Alcohol Use

We can now examine what we know about the conse- quences of long-term (chronic) consumption of alco- hol, over and above the acute effects that were discussed in the last chapter.

Tolerance and Withdrawal As with other CNS depressants, alcohol consumption over a period of time will result in a tolerance effect. On a metabolic level, alcohol dehydrogenase activity dur- ing tolerance becomes higher in the stomach and liver, allowing the alcohol to leave the body somewhat faster; on a neural level, the brain is less responsive to alcohol’s depressive effects. Therefore, if the level of alcohol con- sumption remains steady, individuals feel less of an effect.

As a result of tolerance and the tendency to com- pensate for it in terms of drinking a greater quantity, the chronic alcohol abuser is subject to increased physi- cal risks. There are serious behavioral risks as well; for example, an alcohol-tolerant drinker may consider driv- ing with a BAC level that exceeds the standard for drunk driving, thinking that he or she is not intoxicated and hence not impaired. A person’s driving ability, under these circumstances, will be substantially overestimated.

An alcohol-dependent person’s abrupt withdrawal from alcohol can result in a range of serious physical symptoms beginning from six to forty-eight hours after

the last drink, but estimates of how many people are typ- ically affected vary. Among hospitalized patients, only 5 percent appear to show withdrawal symptoms, whereas studies of alcoholics using outpatient facilities have esti- mated the percentage to be as high as 18. Although the exact incidence may be somewhat unclear, there is less disagreement about what takes place. Physical with- drawal effects are classified in two clusters of symptoms.

The first cluster, called the alcohol withdrawal syndrome, is the more common of the two. It begins with insomnia, vivid dreaming, and a severe hang- over; these discomforts are followed by tremors (the “shakes”), sweating, mild agitation, anxiety (the “jit- ters”), nausea, and vomiting, as well as increased heart rate and blood pressure. In some patients, there are also brief tonic-clonic (grand mal) seizures, as the nervous system rebounds from the chronic depression induced by alcohol. The alcohol withdrawal syndrome usually reaches a peak from twenty-four to thirty-six hours after the last drink and is over after forty-eight hours.

The second cluster, called delirium tremens (DTs), is much more dangerous and is fortunately less common. The symptoms include extreme disorientation and confu- sion, profuse sweating, fever, and disturbing nightmares. Typically, there are also periods of frightening hallucina- tions, when the individual might see snakes or insects on the walls, ceiling, or his or her skin. These effects gener- ally reach a peak three to four days after the last drink. During this time, there is the possibility of life-threatening events such as heart failure, dehydration, or suicide, so it is critical for the individual to be hospitalized and under medical supervision at all times. The current medical practice for treating individuals undergoing withdrawal is to administer antianxiety medication (see Chapter 13) to relieve the symptoms. After the withdrawal period has ended, the dose levels of the medication are gradually reduced and discontinued.13

Liver Disease Chronic consumption of alcohol produces three forms of liver disease. The first of these is a fatty liver, resulting from an abnormal concentration of fatty deposits inside liver cells. Normally, the liver breaks down fats ade- quately, but when alcohol is in the body, the liver breaks down the alcohol at the expense of fats. As a result, fats accumulate and ultimately interfere with the function- ing of the liver. The condition is fortunately reversible, if the drinker abstains. The accumulated fats are gradu- ally metabolized, and the liver returns to normal.

The second condition is alcoholic hepatitis, an inflammation of liver tissue causing fever, jaundice

alcohol withdrawal syndrome: The more common of two general reactions to the cessation of alcohol consumption in an alcoholic. It is characterized by physiological discomfort, seizures, and sleep disturbances.

delirium tremens (DTs): The less common of two general reactions to the cessation of drinking in an alcoholic. It is characterized by extreme disorientation and confusion, fever, hallucinations, and other symptoms.

fatty liver: A condition in which fat deposits accumulate in the liver as a result of chronic alcohol abuse.

alcoholic hepatitis (AL-co-HAUL-ik hep-ah-TIE-tus): A disease involving inflammation of the liver as a result of chronic alcohol abuse.

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 227

(a yellowing of the skin), and abdominal pain, result- ing at least in part from a lower functioning level of the immune system. It is also reversible with abstinence, though some residual scarring may remain.

The third and most serious liver condition is alco- holic cirrhosis, characterized by the progressive devel- opment of scar tissue that chokes off blood vessels in the liver and destroys liver cells by interfering with the cell’s utilization of oxygen. At an early stage, the liver is enlarged from the accumulation of fats, but at later stages it is shrunken as liver cells begin to degenerate (Figure 9.1). Although abstinence helps to prevent fur- ther liver degeneration when cirrhosis is diagnosed, the condition is not reversible except by liver transplanta- tion surgery.

Prior to the 1970s, alcoholic cirrhosis was attributed to nutritional deficiencies that are often associated with an alcoholic’s diet. We know now that, although nutri- tional problems play a role, alcohol itself is toxic to the liver. After a pattern of heavy alcohol consumption of many years, it is possible to develop cirrhosis, even when nutrition is adequate. A major cause of liver cell damage is the toxic accumulation of free radicals, molecule frag- ments that are by-products of acetaldehyde (Chapter 8).

Cirrhosis and other forms of chronic liver disease are collectively ranked as the twelfth leading cause of death in the United States, claiming more than 27,000 lives each year. Most deaths occur in people forty to sixty-five years old. Daily drinkers are at a higher risk of develop- ing cirrhosis than binge drinkers, though this risk may be the result of the relatively larger quantity of alcohol consumed over a long period of time. Generally, patients showing liver damage have been drinking for ten to twenty years. Only 10 to 20 percent of all heavy drinkers develop cirrhosis, however, in contrast to 90 to 100 per- cent who show evidence of either fatty liver or hepatitis. There may be a genetic predisposition to cirrhosis that puts a subgroup of alcoholics at increased risk.14

Cardiovascular Problems About one in every four alcoholics develops cardio- vascular problems owing to the chronic consumption of alcohol. The effects include inflammation and enlargement of the heart muscle, poor blood circula- tion to the heart, irregular heart contractions, fatty accumulations in the heart and arteries, high blood pressure, and stroke. In these cases, the quantity and frequency of drinking far exceeds the standard of “moderate alcohol consumption” which can be a pro- tective factor with regard to cardiovascular disease (see Chapter 8).15

Cancer Chronic alcohol abuse is associated with the increased risk of several types of cancers—in particular, cancers of the pharynx and larynx. Nearly 50 percent of all such cancers are associated with heavy drinking. If alcohol abusers also smoke cigarettes, the increased risk is even more dramatic. An increased risk of liver cancer is also linked to chronic alcoholic abuse, whether or not cir- rhosis is present as well. In addition, alcohol consump- tion is associated with breast cancer in women. There is either a weaker association or no association at all with cancers of the stomach, colon, pancreas, or rectum.

Alcohol is not technically considered a carcinogen (a direct producer of cancer), so why the risks are increased in certain cancer types is at present unknown. It is possi- ble that the increased risk is a combined result of alcohol enhancing the carcinogenic effects of other chemicals and, as is true with the development of hepatitis, alcohol depressing the immune system. With a reduced immune

F I g U r E 9 . 1

The dramatic difference between a healthy liver (top) and a cirrhotic liver (bottom).

alcoholic cirrhosis (AL-co-HAUL-ik seer-OH-sis): A disease involving scarring and deterioration of liver cells as a result of chronic alcohol abuse.

228 ■ Part Three Legal Drugs in Our Society

response, the alcoholic may have a lowered resistance to the development of cancerous tumors.16

Dementia and Wernicke-Korsakoff Syndrome Chronic alcohol consumption can produce longer- lasting deficits in the way an individual solves problems, remembers information, and organizes facts about his or her identity and surroundings. These cognitive defi- cits are commonly referred to collectively as alcoholic dementia and are associated with structural changes in brain tissue. Specifically, there is an enlargement of brain ventricles (the interior fluid-filled spaces within the brain), a widening of fissures separating sections of the cerebral cortex, and a loss of acetylcholine-sensitive receptors. The combination of these effects results in a net decrease in brain mass, as indicated in CT and MRI brain scans, and a decline in overall intelligence, verbal learning and retention, and short-term memory, particu- larly for middle-aged and elderly alcoholics.

Some 50 to 75 percent of all detoxified alcoholics and nearly 20 percent of all individuals admitted to state mental hospitals show signs of alcohol-related dementia. Through abstinence, it is possible to reverse some of the cognitive deficits and even some of the abnormalities in the brain, depending on the age of the alcoholic when treatment begins. As you might suspect, younger alco- holics respond better than older ones.17

A more severe form of cognitive impairment related to chronic alcohol consumption is a two-part disease referred to as Wernicke-Korsakoff syndrome. In Wernicke’s encephalopathy, or simply Wernicke’s dis- ease, the patient shows confusion and disorientation, abnormal eye movements, and difficulties in movement and body coordination. These neurological problems arise from a deficiency in vitamin B1 (thiamine), a nutrient required for neurons in the brain to consume

glucose. Extreme alcoholics may go days or weeks at a time eating practically nothing and receiving calories exclusively from drinking alcoholic beverages.

As a result of thiamine deficiency, large numbers of neurons die in areas of the brain specifically con- cerned with thinking and movement. About 15 percent of patients with Wernicke’s disease, however, respond favorably to large amounts of thiamine supplements in combination with abstinence from alcohol, restoring their previous level of orientation, eye movements, and coordination.

In some cases, Wernicke’s disease patients, whether or not they recover from confusion and motor impair- ments, also display a severe form of chronic amnesia and general apathy called Korsakoff’s psychosis. Such patients cannot remember information that has just been presented to them and have only a patchy mem- ory for distant events that occurred prior to their alco- holic state. They frequently attempt, through a behavior called confabulation, to compensate for their gaps in memory by telling elaborate stories of imagined past events, as if trying to fool others into thinking that they remember more than they actually do.

Thiamine deficiency is linked to Korsakoff’s psy- chosis as well. After being treated with thiamine supple- ments, about 20 percent of patients completely recover their memory and 60 percent partially recover it. Yet the remaining 20 percent, generally the most severely impaired patients and those with the longest history of alcohol consumption, show little or no improvement and require chronic institutionalization.18

Fetal Alcohol Syndrome (FAS) The disorders just reviewed generally have been asso- ciated with consumption of large quantities of alcohol over a long period of time. In the case of the adverse effects of alcohol during pregnancy on unborn children, we are dealing with a unique situation. First of all, we need to recognize the extreme susceptibility of a devel- oping fetus to conditions in the mother’s bloodstream. In short, if the mother takes a drink, the fetus takes one, too. And to make matters worse, the fetus does not have sufficient levels of alcohol dehydrogenase to break down the alcohol properly; thus the alcohol stays in the fetus’s system longer than in the mother’s. In addition, the presence of alcohol coincides with a period of time in prenatal development when critical processes are occur- ring that are essential for the development of a healthy, alert child.

Although it has long been suspected that alcohol abuse among pregnant women might present serious

alcoholic dementia (AL-co-HAUL-ik dih-MEN- chee-ah): A condition in which chronic alcohol abuse produces cognitive deficits such as difficulties in problem solving and memory.

Wernicke-Korsakoff syndrome (VErN-ih-kee KOr-sa- kof SIN-drohm): A condition resulting from chronic alcohol consumption, characterized by disorientation, cognitive deficits, amnesia, and motor difficulty.

thiamine (THY-ah-meen or THY-ah-min): Vitamin B1.

confabulation: The tendency to make up elaborate past histories to cover the fact that long-term memory has been impaired.

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 229

risks to the fetus, a specific syndrome was not estab- lished until 1973, when Kenneth L. Jones and David W. Smith described a cluster of characteristic features in children of alcoholic mothers that is now referred to as fetal alcohol syndrome (FAS). Their studies, and research conducted since then, have shown clearly that alcohol is teratogenic; that is, it produces specific birth defects in offspring by disrupting fetal development during pregnancy, even when differences in prenatal nutrition have been accounted for. Later in life, FAS children show deficits in short-term memory, problem solving, and attentiveness.

Present-day diagnoses of FAS are made on the basis of three groups of observations: (1) prenatal or postnatal growth retardation in which the child’s weight or length is below the 10th percentile, (2) evidence of CNS abnormalities or mental retardation, and (3) a character- istic skull and facial appearance that includes a smaller- than-normal head, small wide-set eyes, drooping eyelids, a flattening of the vertical groove between the mouth and nose, a thin upper lip, and a short upturned nose. If only some of these characteristics are observed, the condition is referred to as partial fetal alcohol syndrome (PFAS). Currently, FAS and PFAS cases are included in a range of diagnoses in which birth defects have been related to maternal alcohol consumption, collectively referred to as fetal alcohol spectrum disorders (FASD).19

The incidence of FAS has been estimated to be approxi- mately 0.2 to 1.5 cases per thousand live births in the general U.S. population, but the rates vary greatly within that population. Incidence is generally higher among Native Americans within the United States. In general, the incidence of FASD is estimated to be three times higher than FAS alone.20

We do not know at present how alcohol causes FASD, except that the greatest risk is in the first tri- mester of pregnancy, especially the third week of gestation when craniofacial formation and brain growth are prominent developmental milestones. Concentrated periods of drinking during this time appear to be very damaging to the fetus. For example, if two mothers consumed a similar overall quantity of alcohol during their pregnancies, but Mother A con- sumed one drink on each of seven days in a week and Mother B consumed all seven drinks on two weekend evenings, then Mother B would have incurred a far greater risk to her child than Mother A (Health Line, page 230).21

Although not all alcoholic mothers give birth to babies with FASD, the research findings are clear: Risks are greatly increased when excessive drinking is taking place. Although an occasional drink may have minimal effects, no one has determined a “safe” level of drinking during pregnancy that would make this behavior risk- free. The objective of prevention, therefore, is to edu- cate women to the dangers of drinking at any level and to encourage complete abstinence from alcohol (as well as other psychoactive drugs) during pregnancy. Since 1989, all containers of alcoholic beverages must contain two warning messages, one of which is that “according to the Surgeon General, women should not drink alco- holic beverages during pregnancy because of the risk of birth defects.”

Fortunately, it has been possible to reduce prena- tal exposure to alcohol through specific public health initiatives. An extensive prevention program, for exam- ple, begun in 1982 in a Pueblo tribe in New Mexico, where the incidence of FAS was 4.1 per 1,000 live births, resulted in the incidence decreased to between 1.3 and 1.6 per 1,000 live births for the years 1984 through 1995.22

The face of a child with fetal alcohol syndrome, showing the wide-set eyes and other features that are characteristic of this condition. The diagnoses of FAS and that of FAE have been subsumed under the more comprehensive term, fetal alcohol spectrum disorders (FASD).

fetal alcohol syndrome (FAS): A serious condition involving mental retardation and facial-cranial malformations in the offspring of an alcoholic mother.

teratogenic (TEr-ah-tuh-JEN-ik): Capable of producing specific birth defects.

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The bad news, however, is that the rates of alco- hol consumption among several other high-risk populations in the United States, such as pregnant smokers, unmarried women, women under the age of twenty-five, and women with the fewest years of edu- cation, remain substantial despite the fact that about 90 percent of women are aware of the potential harm. Nine percent of pregnant women nationwide con- tinue to consume alcohol (Chapter 8). Unfortunately, FASD continues to be the third leading cause of mental retardation not only in the United States but in the entire Western world, exceeded only by Down syndrome and spina bifida. The fact that the develop- ment of alcohol-related fetal defects is entirely pre- ventable makes the incidence of these conditions all the more tragic.23

Patterns of Chronic Alcohol Abuse

When we consider the range of direct and indirect costs to society that result from chronic abuse of alcohol, the price we pay is enormous. These costs include the expense of treatment for alcoholism and of medical intervention for alcohol-related diseases, lost productivity from absentee- ism and decreases in worker performance, treatment for alcohol-related injuries, and the lost value of future earnings of individuals who die prematurely because of alcoholism. The total costs in the United States are esti- mated to be about $224 billion annually, even without taking into consideration the incalculable costs of human suffering that are associated with more than estimated

Health Line Alcoholism Screening Instruments in Professional Use

One of the difficulties in getting information about possible chronic alcohol abuse or alcoholism is the tendency for the individual to deny that problem drinking is going on. It is especially important to find out whether pregnant women are engaging in this behavior, but it is helpful in getting this information from any segment of the population.

A widely used instrument called the CAGE question- naire has four simple questions about drinking: (1) whether the respondent ever felt the need to cut down on one’s drinking, (2) whether it was annoying that people criticized one’s drinking, (3) whether one ever felt guilty about drink- ing, and (4) whether a drink ever was needed first thing in the morning to steady the nerves or get rid of a hangover. The last question is usually referred to as the “Eye-Opener Question” because it identifies the respondent as going through some form of alcohol withdrawal in the morning. The CAGE title refers to the four questions: C for “cut- ting down, “ A for “annoying,” G for “guilty,” and E for “eye-opener.” CAGE test scores have been successful in differentiating problem drinkers from non-problem drink- ers, correctly identifying up to 93 percent of people who are problem drinkers (an indication of the sensitivity of the questionnaire) and up to 76 percent of people who are not (an indication of the specificity of the questionnaire).

Another instrument called the TWEAK question- naire has five basic questions about drinking and has been useful in screening for problem drinking specifically among pregnant women. The questions deal with (1) the number of drinks it takes before the effects of alcohol are felt (an indication of a low threshold for intoxica- tion) or the greatest number of drinks ever consumed

(an indication of alcohol tolerance), (2) whether friends or relatives worried or complained about one’s drinking (tapping into the adverse impact on others), (3) whether alcohol was consumed when first getting up in the morn- ing (indicating alcohol withdrawal similar to the fourth question of the CAGE), (4) whether episodes of drinking could not be later remembered (an indication of a black- out), and (5) whether there had been efforts to cut down on drinking. Again, the TWEAK title refers to letters that are associated with each of the five questions (except for K in “cutting-down”). Researchers have found that TWEAK scores can accurately identify up to 77 percent of women who are problem drinkers and up to 93 percent of women who are not (an indication of the specificity of the ques- tionnaire). While not perfect in predicting the potential for an FAS child, the TWEAK has been a major tool in helping to reduce the incidence of FAS.

Sources: Bernaldt, M. W.; Mumford, J.; Taylor, C.; Smith, B.; and Murry, R. M. (1982). Comparison of questionnaire and laboratory tests in the detection of excessive drinking and alcoholism. Lancet, 6, 325-328. Bradley, K. A.; Boyd-Wickizer, J.; Powell, S. H.; and Burman, M. L. (1998). Alcohol screening questionnaires in women: A critical review. Journal of the American Medical Association, 280, 166–171. Chan, W. K.; Pristach, E. A.; Welte, J. W.; and Russell, M. (1993). Use of the TWEAK test in screening for heavy drinking in three popu- lations. Alcoholism: Clinical and Experimental Research, 17, 1188–1192. . National Institute on Alcohol Abuse and Alcoholism (2002, April). Alcohol alert: Screening for alcohol problems—an update. No. 56. Rockville, MD: National Institute on Alcohol Abuse and Alcoholism.

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 231

80,000 alcohol-related deaths each year. More than three fourths of these costs and more than one half of these deaths are specific results of binge drinking.24

Gender Differences in Chronic Alcohol Abuse As mentioned earlier, chronic alcohol abuse can be found among both men and women. Nonetheless, there are significant gender differences. For example, among persons aged 18 or older, men outnumber women in the incidence of binge drinking by about two to one and heavy alcohol use by about three to one. Overall, women are more vulnerable to alcohol-related organ damage. Whether this higher risk results from differ- ences in the pattern of drinking or from differences in the way alcohol is processed in a woman’s body is at present unknown.25

Figure 9.2 shows a state-by-state analysis of alcohol- related problems as measured by the prevalence rate for binge drinking.26

Alcohol Abuse among the Elderly There is a widely held misconception that alcohol abuse is not much of a problem with the elderly. On the basis of careful studies addressing the problem of chronic alcohol abuse among the elderly, it has been estimated that approximately 9 percent of the elderly

population have alcohol problems, as indicated by con- suming four or more drinks in a single day or more than thirty per month. An analysis of Medicare records has indicated that more people over the age of sixty-five are hospitalized each year for alcohol-related problems than for heart attacks.27

One of the reasons for the underreporting of this problem is that we typically use the quantity of alco- hol consumed as a primary index of alcoholism, and alcohol consumption does indeed decline with age. Yet, because of the changes in alcohol biotransforma- tion over a lifetime, three drinks consumed at age sixty can be equivalent in their effects to four times as many drinks for someone at age twenty. In addition, the indications of social and occupational problems, tra- ditionally part of the criteria for alcoholism, are often irrelevant for an elderly drinker. There would be no incidence of drunk driving if the person is no longer driving, no job supervisor to notice a decline in work performance, and frequently no spouse to complain of social difficulties. Finally, the occurrence of blackouts or symptoms of Wernicke-Korsakoff syndrome may be misdiagnosed simply as an indication of senility or the onset of Alzheimer’s disease.

A number of problems particularly affect the elderly who chronically abuse alcohol. One problem is the risk of the alcohol interacting with the many medications that the elderly typically take. Another is the risk of com- plications for already existing medical conditions, such as gastrointestinal bleeding, hypertension and cardiac

F I g U r E 9 . 2

State-by-state prevalence rates for binge drinking among adults in 2010.

Source: Centers for Disease Con- trol and Prevention (2012). Vital signs: Binge drinking prevalence, frequency, and intensity among adults—United States, 2010. Morbidity and Mortality Weekly Report, 61, 14–19.

Prevalence (%) 18.7–25.6 16.8–18.6 10.9–16.7 Data unavailable

DC

232 ■ Part Three Legal Drugs in Our Society

arrhythmias, osteoporosis, depression, and cognitive impairment-related disorders.

There is growing recognition that treatment pro- grams for alcoholism ought to be tailored to the special needs of the elderly; frequently the traditional treatment programs that benefit much younger individuals do not work well with older people. Many seniors were brought up in an era when highly negative attitudes toward drink- ing prevailed, so if they are drinking themselves, they feel stigmatized and resist treatment. On a brighter note, however, it has been found that when treatment pro- grams are designed specifically with the elderly in mind, older alcoholics often respond well to treatment.28

The Family Dynamics of Alcoholism: A Systems Approach Alcoholism, like any form of drug abuse, is an especially traumatizing experience for the families involved. For every one person who has a problem with alcohol, there are, on average, at least four others who are directly affected on a day-to-day basis. It is therefore important to examine some of these effects on particular family members. Since the 1950s, a systems approach has advocated looking at how the alcoholic and other mem- bers of the family interact.29 We discussed one of these aspects earlier in the chapter in connection with the adverse effects of enabling behavior on the alcoholic. Another important aspect related to an alcoholic’s fam- ily is the possibility of codependency.

Since the early 1980s, the concept of codepen- dency has gained widespread attention as a way of understanding people who live on a day-to-day basis with an alcoholic or any individual with a drug depen- dence. Definitions vary but most identify four essential features. In members of the family of an alcoholic, ther- apists have observed (1) an over-involvement with the alcoholic, (2) obsessive attempts to control the alcohol- ic’s behavior, (3) a strong reliance on external sources of self-worth, through the approval of others, and (4) an

attempt to make personal sacrifices in an effort to improve the alcoholic’s condition.30

If people in a relationship with a codependent act badly, the codependent believes that he or she is respon- sible for their behavior. Because codependency is con- sidered to be a learned pattern of thinking rather than an innate trait, the goal of therapy is to teach the codepen- dent person to detach himself or herself from the alco- holic and begin to meet his or her own needs rather than being controlled by the value judgments of others.31

Some professionals, however, have questioned the validity of the codependency concept. They have argued that by labeling a person a codependent, the therapist is promoting feelings of helplessness or victimization in these individuals that might not have existed before. Indeed, the idea of codependency might diminish the person’s incen- tive to begin efforts to take control over his or her life by reinforcing the feeling that he or she is “doomed to suf- fer.” Critics also have pointed out that actual patterns of codependency may not be specific to particular indi- viduals but, rather, occur in practically everyone and that codependency may simply reflect the problems of living in modern society, only now we have found language to describe our tendency to explain our own failures by blam- ing other people. Nonetheless, despite the criticisms, co- dependency has become a central concept in therapies that consider family issues in the treatment of alcoholism.32

Children of an Alcoholic Parent or Parents Considering the immense impact that our parents have in our lives, it is understandable that an alcoholic family has distinct negative consequences on the psychological development of the children in that family. As a result, children of alcoholics (COAs) have a higher statistical risk of becoming alcoholics than do children of nonal- coholics. Whether this increased risk is genetically or environmentally based is a complex issue that will be reviewed in the next section.

An equally important and independent risk fac- tor may be the specific behavioral and physiological reactions a person has to alcohol itself. Men who at age twenty have a relatively low response to alcohol, in that they need to drink more than other people to feel intoxicated, carry a higher risk of becoming alcoholic by the time they are thirty, regardless of their pattern of drinking at an earlier age and regardless of their parents’ drinking. Sons of alcoholics having a low response to alcohol have a 60 percent chance of becoming alcohol- ics, compared with a 42 percent chance for sons of alco- holics in general. Sons of nonalcoholics having a low

systems approach: A way of understanding a phenomenon in terms of complex interacting relationships among individuals, family, friends, and community.

codependency: The concept that individuals who live with a person who has an alcohol (or other drug) dependence suffer themselves from difficulties of self- image and impaired social independence.

children of alcoholics (COAs): Individuals who grew up in a family with either one or two alcoholic parents.

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 233

response to alcohol have a 22 percent chance of becom- ing alcoholics, compared with an 8 to 9 percent chance for sons of nonalcoholics in general.

The combination of these two risk factors—family history and a low response to alcohol—is obviously the worst scenario for a development of alcoholism, at least in males. Nonetheless, we should remember that a large proportion of people still do not become alcoholics, even with both risk factors present. The question of what protective factors may account for the resilience of some high-risk individuals with regard to alcoholism contin- ues to be a major subject of alcoholism research.33

The Genetics of Alcoholism

For centuries, a common observation has been that alcoholism tends to run in families. Today, a more specific question can be addressed: To what extent is alcoholism genetically determined (through the genes of the parents) and to what extent is it environmentally determined (through the living conditions in which the offspring have been brought up)?

One approach is to examine the inheritance pattern in a family tree. It is impossible, however, to tease out the separate genetic (nature) and environmental (nurture) factors from information of this kind. For more precise answers, we can turn to cases of adopted children and compare the behavior of their lives with the behavior in the lives of either their biological or adoptive parents. In 1981, an extensive research study in Sweden examined the adoption records of approximately three thousand children who had alcoholic biological parents but lived with nonal- coholic adoptive parents. The results showed that a larger percentage of these children become alcoholics than would be seen in the general population. The greater inci- dence was present even when the children had been raised by their adoptive parents immediately after being born, indicating that a strong genetic component was operating.

There were, however, two subgroups among those children who eventually became alcoholics. One sub- group, called Type 1 alcoholics, developed problem drinking later in life and generally functioned well in society. In addition to a genetic predisposition toward alcoholism, there was for this subgroup a strong envi- ronmental factor as well. Whether the child was placed in a middle-class or a poor adoptive family influenced the final outcome. A second subgroup, called Type 2 alcoholics, developed alcoholism earlier in life and had significant antisocial patterns of behavior. A strong genetic component was operating in this subgroup, and because the socioeconomic status of the adoptive family

made no difference in the outcome, we can conclude that environmental factors played a negligible role. Table 9.1 gives a more complete picture of the charac- teristics associated with Type 1 and Type 2 alcoholics.34

The study of twins is another source of informa- tion about the genetic and environmental influences in alcoholism. Probably the most important piece of data is the concordance rate for alcoholism in pairs of identi- cal twins—that is, how likely one member of a pair is to be alcoholic if the other member is. The concordance rate has been found to be between 50 and 60 percent. If genetics were the whole story in determining the inci- dence of alcoholism, the concordance rate would have been 100 percent.

If we look closely at the type of alcoholic involved and whether the alcoholic is male or female, the data from twin studies are similar to those found in the

TAbLE 9.1

Two types of alcoholics

CHArACTErISTICS TYpE 1 TYpE 2

Usual age at onset (late onset) after 25

(early onset) before 25

Inability to abstain infrequent frequent

Fights and arrests when drinking

infrequent frequent

Psychological dependence (loss of control)

infrequent frequent

Guilt and fear about alcoholism

frequent infrequent

Novelty-seeking personality low high

Tendency to use alcohol to escape negative feelings

high low

Tendency to use alcohol to achieve positive feelings

low high

Gender male and female

male only

Extent of genetic influences moderate high

Extent of environmental influences

high low

Serotonin abnormalities in the brain

absent present

Source: Updated from Cloninger, C. R. (1987). Neurogenetic adaptive mechanisms in alcoholism. Science, 236, 410–416.

concordance rate: The likelihood that one member of a twin or family relation will have a condition if the other member has it.

234 ■ Part Three Legal Drugs in Our Society

adoption research. For example, the concordance rate for identical twins has been found to be signifi- cantly higher than the concordance rate for fraternal twins when one member of the pair is a male alco- holic whose drinking problems started in adolescence (in other words, a Type 2 alcoholic). For female and male alcoholics whose drinking problems started after adolescence (the Type 1 subgroup), a comparison of concordance rates shows that genetic factors played a lesser role.35

Recent studies of alcoholism have brought together genetic and environmental factors by identifying two neurochemical systems in the brain (see Chapter 3). The first system involves the release of corticotropin- releasing factor (CRF) in the hypothalamus. Increased CRF levels have been observed during stress-induced alcohol-drinking behavior and during alcohol with- drawal. The second system involves an increased glutamate activity during alcohol withdrawal, presum- ably causing behavior related to alcohol craving. In short, studies in both animals and humans have led to the idea that an increased risk of alcoholism may be a result of an interaction between these two systems (see Figure 9.3). It is possible that that abnormal glutamate- related activity may be responsible for increased levels of CRF (Figure 9.3).36

The Concept of Alcoholism as a Disease

In contrast to the days when alcoholism was considered a moral failure or worse, the opinion today is that alco- holism is best characterized as a disease, with the con- sequence being that the alcoholic individual should be treated rather than punished. This viewpoint, by the way, was advanced as early as the 1780s by Benjamin Rush (see Chapter 8). The modern-day concept of alcoholism as a disease can be credited principally to the writings of E. M. Jellinek in the late 1940s. Jellinek proposed that alcohol dependence progressed through a natural sequence of stages, much as a physical illness develops.37 In more recent interpretations, the disease concept has moved away from the idea that all alcoholics follow a common path (many of Jellinek’s ideas have not been confirmed) to a more general focus on the biological fac- tors that might differentiate alcoholics from nonalcohol- ics. In addition, the disease concept has led to the idea that alcoholics are fundamentally out of control and that abstinence is the only answer to their recovery.38

Since 1957, the American Medical Association has defined alcoholism as a disease, and other health orga- nizations have adopted a similar position. Nonetheless,

F I g U r E 9 . 3

The contributions of genetic and environmental factors to the development of alcohol abuse and neurochemical adaptations that lead to alcohol craving and the development of alcoholism.

Source: Stacy, D.; Clarke, T-K.; and Schumann, G. (2009). The genetics of alcoholism. Current Psychiatry Reports, 11, p. 366.

Chronic alcohol use

Hyperglutamatergic state

Genetic susceptibility

Alcoholism

Genetic susceptibility

Alcohol craving

Increased CRF activity

Genetic susceptibility

Environmental Factors (e.g., Stress)

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 235

as reasonable as this position might sound, the disease concept has created something of a dilemma among professionals concerned with the treatment of alco- hol abuse. It places the burden on physicians to deal with the alcoholic through medical interventions, and unfortunately the medical profession is frequently ill equipped to help. A study in 2000, for example, found that 94 percent of a group of primary care physicians failed to make a correct diagnosis of early-stage alcohol abuse when presented with symptoms typical of this condition. Only a small percentage, approximately one out of five, considered themselves “very prepared” to diagnose alcoholism in the first place.39

Important legal considerations also cloud this issue. Can we say, for example, that an alcoholic is legally absolved from a crime or a legal obligation because he or she is afflicted with this disease? These and related issues will be explored later in the chapter in Health Line (page 238) and in Point/Counterpoint III (pages 246–247).

Approaches to Treatment for Alcoholism

Alcoholism, as should be clear at this point, is a study in diversity, and it makes sense that there might be some advantage in matching alcoholics with certain charac- teristics to specific forms of treatment. One treatment program might be best suited for one subgroup, another for another subgroup. A major eight-year study spon- sored by NIAAA, known as Project MATCH, was com- pleted in 1997 to address the relative effectiveness of three psychosocial approaches to alcoholism treatment:

■ Cognitive Behavioral Coping Skills Therapy, oriented toward correcting poor self-esteem and distorted, self- defeating thinking.

■ Motivational Enhancement Therapy, helping to improve one’s readiness to quit drinking.

■ Twelve-step Facilitation Therapy, designed to educate clients with the philosophy of Alcoholics Anonymous and encourage their participation.

While improvements were noted for all three treat- ment approaches, none of the approaches were con- sidered superior to the others in most measures of effectiveness. However, in terms of the percentage maintaining complete abstinence, the Twelve-step facilitation group showed greater improvement than the two other groups, a difference that continued across three years.40

Since then, approaches in treatment have gone beyond an exclusive focus on psychosocial issues in alco- holism, taking advantage of an increased understanding of neurochemical changes that occur in the develop- ment of alcoholism. Today, both biologically-based and psychosocial-oriented treatments are available, often in conjunction with each other. In this section, we will examine alcoholism treatment in terms of these two broad areas: biological interventions, which involve medications, and psychosocial interventions, such as Alcoholics Anonymous and other self-help programs.

Biologically Based Treatments The earliest biologically based treatment was the intro- duction of disulfiram (brand name: Antabuse), based on the idea that if a drug induced an aversive reaction when alcohol is consumed, then consumption would be avoided. When applied to alcoholism treatment, the prediction was that the problems of alcoholism would be reduced as a result. Disulfiram, taken orally as a pill once each day, inhibits aldehyde dehydrogenase, allowing acetaldehyde to build up in the bloodstream. Individuals who consume alcohol in combination with disulfiram experience a flushing of the face, rapid heart rate and palpitations, nausea, and vomiting. These effects are brought on not only by consuming alcoholic beverages but also by ingesting alcohol in other forms, such as mouthwashes and cough mixtures, and even by the absorption of aftershave lotions and shampoos through the skin.

Clearly the symptoms caused by a combination of disulfiram and alcohol can be a powerful short- term deterrent to alcoholic drinking, but the question is whether this kind of aversion therapy is an effective treatment over the long run. Careful studies in which disulfiram has been administered to large numbers of alcoholics indicate that it is not effective when it is the sole treatment. One major problem is that alcohol- ics must take the drug regularly every day, and because disulfiram does nothing to reduce the alcoholic’s crav- ing for alcohol, compliance rates are low. The consensus among professionals in this field is that disulfiram can be useful in a subgroup of higher-functioning alcohol- ics with exceptionally high motivation to quit drinking; for others, disulfiram can be useful as a transitional treat- ment until other support programs are in place.41

disulfiram (dye-SULL-fih-ram): A medication that causes severe physical reactions and discomfort when combined with alcohol. Brand name is Antabuse.

236 ■ Part Three Legal Drugs in Our Society

A more direct approach to treatment than aversion therapy has been to reduce the actual craving for alco- hol on a neurochemical level. As noted in Chapter 8, evidence suggests that alcohol dependence is related to neural activity in the same dopamine-releasing recep- tors in the nucleus accumbens that have been impli- cated in heroin craving, as well as in craving for cocaine and nicotine. This parallel to heroin dependence sug- gests that opioid receptor antagonists in this region of the brain, such as naltrexone (brand name: ReVia) and nalmefene (brand name: Revex), should be useful in alcohol-dependence treatment.

An extended-release injectable form of naltrexone (brand name: Vivitrol), administered on a monthly basis, was FDA-approved for alcoholism treatment in 2006. The obvious advantage is that individuals do not have to remember to take their medication on a daily basis. Problems associated with individuals skipping their medication are eliminated, and there can be a more intensive concentration on the counseling compo- nent of recovery. The advantage of an extended-release naltrexone for treating alcohol dependence parallels that of extended-release formulations of buprenor- phine (Subutex, Suboxone) for treating heroin abuse (Chapter 5). Another approach in treatment has been to focus on the regulation of GABA, in a manner simi- lar to the way gamma vinyl-GABA (Vigabatrin) is used for cocaine-abuse treatment (Chapter 4). Acamprosate (brand name: Campral) was FDA-approved in 2004 for this purpose. Recent studies indicate the usefulness of anticonvulsant medications such as topiramate (brand name: Topamax), levetiracetam (brand name: Keppra), and gabapentin (brand name: Neurontin). The com- bination treatment of gabapentin and naltrexone has shown particular promise.

Still another approach has focused on the role of serotonin levels in the brains of alcoholics. Since

early-onset (Type 2) alcoholism differs from late-onset (Type 1) alcoholism owing to its association with sero- tonin abnormalities in the brain (see Table 9.1), a drug that reduces serotonin levels, such as ondansetron (brand name: Zofran), typically used as an antinausea medication, should be beneficial in treating this sub- group. This prediction has been confirmed. Among Type 2 alcoholics, Zofran has significantly reduced their drinking behavior and provided a longer period of abstinence.42

TAbLE 9.2

The famous Twelve Steps of Alcoholics Anonymous

1. We admitted we were powerless over alcohol—that our lives had become unmanageable.

2. Came to believe that a Power greater than ourselves could restore us to sanity.

3. Made a decision to turn our will and our lives over to the care of God as we understood Him.

4. Made a searching and fearless moral inventory of ourselves.

5. Admitted to God, to ourselves, and to another human being the exact nature of our wrongs.

6. Were entirely ready to have God remove all these defects of character.

7. Humbly asked Him to remove our shortcomings.

8. Made a list of all persons we had harmed and became willing to make amends to them all.

9. Made direct amends to such people wherever possible, except when to do so would injure them or others.

10. Continued to take moral inventory and when we were wrong, promptly admitted it.

11. Sought through prayer and meditation to improve our conscious contact with God, as we understood Him, praying only for knowledge of His will for us and the power to carry that out.

12. Having had a spiritual awakening as a result of these steps, we tried to carry this message to alcoholics, and to practice these principles in all our affairs.

Source: The Twelve Steps are reprinted with permission of Alcoholics Anonymous World Services, Inc. (AAWS). Permission to reprint the Twelve Steps does not mean that AAWS has reviewed or approved the contents of this publication, or that AAWS necessarily agrees with the views expressed herein. A.A. is a program of recovery from alcoholism only—use of the Twelve Steps in connection with programs and activities which are patterned after A.A., but which address other problems, or in any other non-A.A. context, does not imply otherwise.

naltrexone (nal-TrEX-ohn): A long-lasting opioid antagonist for the treatment of alcoholism. Brand name is ReVia. Brand name for an extended-release injectable form is Vivitrol

nalmefene (nal-MEH-feen): A long-lasting opioid antagonist for the treatment of alcoholism. Brand name is Revex.

acamprosate (A-cam-prO-sate): A GABA-related drug for the treatment of alcoholism. Brand name is Campral.

ondansetron (on-DANS-eh-tron): A serotonin-related drug for the treatment of alcoholism. Brand name is Zofran.

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 237

Alcoholics Anonymous The best-known treatment program for alcoholism is Alcoholics Anonymous (AA). Founded in 1935, this organization was conceived basically as a fellowship of alcoholics who wish to rid themselves of their problem drinking by helping one another maintain sobriety. The philosophy of AA is expressed in the famous Twelve Steps (Table 9.2). Members must have acknowledged that they were “powerless over alcohol” and that their lives had become unmanageable, and must have turned their will and their lives over “to the care of God as we understood Him.” As the steps indicate, there is a strong spiritual component to the AA program, although the organization vigorously denies that any religious doc- trine prevails (Portrait).

AA functions as a type of group therapy with each member oriented toward a common goal: the mainte- nance of abstinence from alcohol despite a powerful and continuing craving for it. All meetings are com- pletely anonymous (only first names are used in all communications), and the proceedings are dominated by members recounting their personal struggles with alcohol, their efforts to stop drinking, and their sup- port for fellow alcoholics in their own struggles. New members are encouraged to pair up with a sponsor,

p O r T r A I T Bill W. and Dr. Bob—Founders of Alcoholics Anonymous

When they met in the spring of 1935, the backgrounds of William Griffith Wilson (left) and Dr. Robert Smith (right) could not have been more different, but they shared an important problem. They were both alcoholics, and their lives had come apart because of it. Wilson had gone from being a successful busi- nessman, whose investments on Wall Street during the 1920s had made him rich, to a penniless failure after losing his entire fortune in the 1929 crash. Whether rich or poor, he had been a drunk, but his poverty made the condi- tion worse. In 1934 Wilson was admit- ted to Towns Hospital in New York City and agreed to subject himself to the “belladonna cure,” a treatment based on his receiving morphine and the powerful hallucinogen belladonna. Under the influence of this combina- tion of drugs, Wilson experienced “his spiritual awakening.” He later wrote,

In the wake of my spiritual expe- rience there came a vision of a society of alcoholics. If each suf- ferer were to carry the news of the scientific hopelessness of alcohol- ism to each new prospect, he might be able to lay every newcomer wide

open to a transforming spiritual experience.

For several months, following his newfound mission in life, Wilson sought out drunks to “work on.” On a trip to Akron, Ohio, where he was seeking a new job, he was introduced by mutual friends to a proctologist and surgeon named Dr. Robert Smith.

Smith’s alcoholism had wrecked a distinguished medical career, and in 1935, he was in severe financial straits. Wilson’s determination com- bined with Smith’s desperation led to their taking on the task of keeping each other sober and helping oth- ers do the same. On June 10, 1935 (the official date of the founding of Alcoholics Anonymous), Smith took his last drink. By 1939, Wilson had finished writing the Twelve Steps and an extended explanation of the AA philosophy, known today as the “Big Book.” Wilson and Smith had dis- covered that they were most success- ful in keeping alcoholics abstinent when the latter attended meetings on a regular basis and were assured of complete privacy and anonymity.

Wilson became Bill W., and Smith became Dr. Bob.

It was not until the 1940s that AA began to be nationally known. The Saturday Evening Post, one of the lead- ing magazines of the day, gave AA its first real publicity break, publishing an article about the organization that generated an avalanche of responses and a dramatic increase in member- ship. During this time, AA adopted the an untitled prayer, originally composed by the American theologian Reinhold Niebuhr. It has since been commonly referred to as The Serenity Prayer, recited millions of times in AA and other twelve-step program meetings through- out the world: “God grant me the seren- ity to accept the things I cannot change, the courage to change the things I can, and the wisdom to know the difference.”

Sources: Alcoholics Anonymous comes of age: A brief history of AA (1959). New York: Alcoholics Anonymous World Services. Alibrandi, L.A. (1982). The fellowship of Alcoholics Anonymous. In E. M. Pattison and E. Kaufman (Eds.), The encyclopedic handbook of alcohol- ism. New York: Gardner Press, p. 979. Cheever, S. (2004). My name is Bill. New York: Simon and Schuster.

Alcoholics Anonymous (AA): A worldwide organization devoted to the treatment of alcoholism through self-help groups and adherence to its principles, which include absolute abstinence from alcohol.

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typically a more experienced AA member who has successfully completed the Twelve Steps and can serve as a personal source of support on a day-to-day basis. According to AA, no alcoholic is ever cured but is only recovering, and the process of recovery contin- ues throughout that person’s life. In this view alcohol- ism is a disease, and relapse from sobriety can occur at any moment. The question of whether an alcoholic is totally unable to control his or her drinking is exam- ined in Health Line.

AA has grown to more than 114,000 groups and more than 2 million members worldwide, although it is difficult to get a precise count because the organi- zation is deliberately structured very loosely. Perhaps more important than its size is the powerful impact

AA has had not only on the way we deal with alco- holism but also on the way we consider treatment for any compulsive behavior in general. Over the years, the twelve-step program has become a generic con- cept, as the precepts and philosophy of AA have been widely imitated. There are chapters of Gamblers Anonymous, Nicotine Anonymous, Narcotics or Cocaine Anonymous, and Overeaters Anonymous, all based on the AA model. In addition, there are two specialized fellowship organizations, Al-Anon for relatives and friends of alcoholics and Alateen for teenagers living with an alcoholic family mem- ber. These programs adopt a twelve-step approach to identifying and dealing with the dysfunctionality of an alcoholic family.

Health Line Is Controlled Drinking Possible for Alcoholics?

One of the most intensely debated questions in the field of alcoholism treatment has been whether it is possible for alcoholics to achieve a level of “controlled drinking” with- out falling back into a state of alcohol dependence.

On one side are well-entrenched organizations such as Alcoholics Anonymous (AA) and the National Institute on Alcohol Abuse and Alcoholism, as well as many other organizations that assert that alcoholism is an irreversible disease, that abstinence is the only answer, and that even the slightest level of alcohol consumption will trigger a cascade of problems that the alcoholic is constitutionally incapable of handling.

On the other side are groups, represented in greater numbers in Canada and Europe than in the United States, asserting that uncontrolled drinking is a reversible behavioral disorder and that for many alcoholics the pro- motion of total abstinence as a treatment goal is a serious obstacle to their success in rehabilitation. The organiza- tion Moderation Management (MM) is an example of this type of therapeutic approach.

Some of the early controlled-drinking studies had so many methodological flaws that the abstinence-only groups were justified in denouncing them. But later research, using carefully randomized assignment of alco- holic subjects to either an abstinence-oriented treatment or a controlled-drinking treatment, has shown that long- term results are comparable for the two groups. This is not to say that the prospects are wonderful for either of them; sadly, the odds against long-term recovery from alcohol- ism are still higher than the odds in favor of it, no matter

what the treatment. But it does appear that controlled drinking can occur.

How many alcoholics can manage to achieve a con- tinued level of nonproblem drinking? Percentages vary from 2 to 10 to 15 percent, although the lower figure is probably more accurate for those individuals with severe alcoholic difficulties. Perhaps a more important point is that no one knows how to predict whether an alcohol abuser will be one of that small number of successful con- trolled drinkers. Obviously, most alcoholics are convinced that they will be among the lucky ones. How does an alcoholism-treatment counselor handle this? A prominent expert offers one strategy:

My own perspective is that there is little sense in losing a client by a standoff on this issue. . . . It has been my clini- cal experience that an unsuccessful trial at “controlled drinking” may be a more persuasive confrontation of the need for abstinence than any amount of argumentation between therapist and client.

Sources: Hester, R. K., and Miller, W. R. (1989). Self- control training. In R. K. Hester and W. R. Miller (Eds.), Handbook of alcoholism treatment approaches. New York: Pergamon Press, pp. 141–149. Miller, W. R. (1989). Increasing motivation for change. In R. K. Hester and W. R. Miller (Eds.), Handbook of alcoholism treatment approaches. New York: Pergamon Press, pp. 67–80. Quotation on p. 77. Sobell, M. B., and Sobell, L. C. (1978). Behavioral treatment of alcohol problems: Individualized therapy and controlled drinking. New York: Plenum.

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 239

Despite its stature as the preeminent approach to treatment, there are relatively few scientific appraisals of the overall effectiveness of AA. One of the principal obstacles to evaluation is the anonymity guaranteed to all members, which makes it difficult to conduct well- controlled follow-up studies on how well AA members are doing. Nonetheless, AA is widely regarded in the field of alcohol rehabilitation as a beneficial self-help approach, particularly when it is combined with other treatments, such as individual counseling and medi- cal interventions.43 It has been pointed out that AA employs four factors that are widely shown to be effec- tive in preventing relapse in alcohol dependence: (1) the imposition of external supervision, (2)  the substitution of dependence on a group activity for

An anonymous group of men and women at a typical Alcoholics Anonymous meeting.

Drugs . . . in Focus

The Non-Disease Model of Alcoholism and Other Patterns of Substance Abuse Despite the “official” description of alcoholism as a disease by the American Medical Association and many international health organizations, the concept of alco- holism as a disease remains controversial and continues to attract vigorous criticism. As Erich Goode has put it, the non-disease theorists assert that alcoholics (as well as other drug abusers) are “. . . not ‘sick,’ but are rational, problem-solving human beings attempting to carve out a meaningful existence in a harsh and seemingly unyield- ing environment.” Others have warned that the disease model encourages alcoholics to assume a passive stance, depending solely on the advances of modern medicine to save the day, and that acceptance of the disease model often leads to making excuses for one’s behavior rather than changing it. As a one-liner expresses it, “There’s nothing wrong with being an alcoholic, if you’re doing something about it.”

The “disease versus non-disease” debate has inevi- table consequences for the ways in which we choose to respond to the problem. Non-disease theorists view the prevailing majority opinion as unfortunately leading to a marginalization of alcoholics, reducing them to a small group of afflicted, biologically predestined individuals, rather than seeing these people in the context of the way all of us behave to one degree or another. In the words of

non-disease advocate Stanton Peele, this attitude fosters a “coercive, one-size-fits-all . . . disease treatment system of hospitals, Alcoholics Anonymous, and the twelve steps, which are increasingly administered within the framework of the law enforcement system.” He views the disease model as leading to the assumption that all drinking must cease (a position held by AA), instead of to the encour- agement of controlled levels of drinking, as advocated by Moderation Management (MM). He also argues that without the disease model of alcoholism and other drug abuse, it is possible to focus on “the larger question of why some people seek to close off their experience through a comforting, but artificial and self-consuming relationship with something external to themselves. In itself, the choice of object is irrelevant to this universal process of becoming dependent.”

Further discussion of the disease model of alcoholism can be found in the form of a simulated debate in Point/ Counterpoint III on pages 246–247.

Sources: Goode, E. (1999). Drugs in American society (5th ed.). New York: McGraw-Hill College, quotation on p. 350. Kinney, J. (2012). Loosening the grip: A handbook of alcohol information (12th ed.). New York: McGraw-Hill, pp. 89-92. Peele, S. (1995). Assumptions about drugs and the marketing of drug policies. In W. K. Bickel and R. J. DeGrandpre (Eds.), Drug policy and human nature. New York: Plenum, pp. 199–220, first quotation on p. 214. Peele, S., and Brodsky, A. (1975). Love and addiction. New York: Taplinger Publishing, second quotation on p. 55.

240 ■ Part Three Legal Drugs in Our Society

dependence on drug-taking behavior, (3) the devel- opment of caring relationships, and (4) a heightened sense of spirituality.44

SMArT recovery In contrast to AA, the self-help program SMART Recovery assumes that people do not need to believe they are “powerless over alcohol” or submit to “a Power greater than ourselves” (phrases taken from the Twelve Steps) to recover from alcoholism. Instead, the dominant philosophy is that individuals have the power themselves to overcome anything, including drinking. Unlike AA, SMART Recovery discourages labeling in general; a per- son is not required to call himself or herself an alcoholic to achieve success in recovery. The strategy is based on

rational emotive behavior therapy (REBT), an approach developed by the psychologist Albert Ellis that empha- sizes rooting out irrational thoughts, emotions, and beliefs that prevent the achievement of personal goals.

Another major difference is that SMART Recovery insists on professional involvement in its program, with a professional adviser (often a clinical psychologist) helping members learn the fundamentals of REBT. No reference is made to God or a higher power; the objec- tive is “NHP (no higher power) sobriety.” The goal is that within a year and a half, members will be able to maintain sobriety without going to meetings. In con- trast, AA members are encouraged to continue going to meetings for the rest of their lives.

Since 1990, there has been increased interest in sec- ular (nonreligious) approaches to self-help alcoholism treatment such as that practiced by SMART Recovery. Other examples include Men for Sobriety (MFS), Women for Sobriety (WFS), Moderation Management (MM), and Secular Organization for Sobriety (SOS). Nonetheless, recent research has indicated that alcohol- ics benefit from participation in AA programs, regardless of their religious beliefs (Drugs . . . in Focus).45

Chronic Alcohol Abuse and Alcoholism in the Workplace

It has been estimated that about 15 percent of the peo- ple in the American work force (19.2 million workers) have used alcohol within two hours of reporting to work or during the workday, worked under the influence of alcohol or worked with a hangover at least once in the previous 12 months. The prevalence rates of alcohol impairment at the workplace are higher among men than women, higher for white employees than minor- ity employees, higher for younger than older employ- ees, and higher for unmarried than married employees. Alcohol impairment is also most frequently reported by individuals in the arts/entertainment/sports/media indus- tries, food preparation and service jobs, and building and grounds maintenance occupations. Individuals with jobs that would be seriously affected if alcohol impairment were present, such as workers in construction/extraction industries and transportation/material-moving industries, do not show a significantly higher prevalence rate of alco- hol impairment at work than the work force at large.46

Given the adverse impact of chronic alcohol abuse on a range of workplace behaviors, it makes sense that corporations, hospitals, the armed services, and other large organizations should benefit by establishing work- place programs specifically designed for employees

SMArT recovery: A treatment program for abuse of alcohol and other drugs that emphasizes a nonspiritual philosophy and a greater sense of personal control in the abuser. SMART stands for “Self-Management And Recovery Training.”

Quick Concept Check 9.2

Understanding Alcoholics Anonymous Check your understanding of the principles and philoso- phy of Alcoholics Anonymous by indicating whether each of the following statements would be subscribed to by Alcoholics Anonymous.

1. I have always had the power to control my drinking.

yes no

2. I must put myself in the hands of a Higher Power if I am to be sober for the rest of my life.

yes no

3. It is possible to be cured of alcoholism.

yes no

4. I am capable of having a drink once in a great while without slipping back into alcoholism.

yes no

5. The more meetings I attend, the better chance I have of remaining sober.

yes no

Answers: 1. no 2. yes 3. no 4. no 5. yes

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 241

who need help. Two major efforts address this problem. The first is employer-sponsored employee assistance programs (EAPs), and the second is union-supported member assistance programs (MAPs). EAPs have been established as a way of increasing the productivity of the organization, whereas MAPs are oriented toward enhancing the welfare of the individual worker.

In either case, a major thrust of workplace interven- tions has been to change the culture of drinking within the organization. For example, problems arise because employees tend to drink heavily in order to conform to workplace drinking norms. Within a heavy drinking cul- ture, employees are more likely to use alcohol to cope with stress and feelings of alienation. Gender harass- ment, characterized by behaviors directed at female employees that convey hostile and degrading attitudes toward women, is associated with the proportion of male employees identified as heavy or “at-risk” drinkers,

and the association is stronger when alcohol consump- tion is considered a common pattern of behavior during lunch or other meal breaks. In other words, a permissive, alcohol-oriented culture at work exacerbates an already serious workplace problem.

Workplace EAPs and MAPs will be examined in Chapter 17 in the larger context of treatment for the substance abuse in general.47

employee assistance programs (EAps): Corporate or institutional programs for workers or employees to help them with alcohol or other drug-abuse problems.

member assistance programs (MAps): Institutional programs for workers or employees to help them with alcohol or other drug-abuse problems, set up by established unions within the organization and tailored to meet the needs of union members.

Summary

Alcoholism: Stereotypes, Definitions, and Life problems ● Alcoholism is a multidimensional condition that is

typically defined in terms of four major life problems: (1) problems associated with a preoccupation with drinking, (2) emotional problems, (3) vocational, social, and family problems, and (4) physical problems.

Alcohol Abuse and Alcohol Dependence ● According to health professionals, alcohol abuse is

defined in terms of (1) persistent physical, social, or occupational problems that have become associated with alcohol use and (2) recurring use of alcohol in physically hazardous situations. Alcohol dependence is defined in terms of uncontrolled alcohol intake, unsuccessful efforts to reduce alcohol use, life prob- lems, and alcohol tolerance and withdrawal.

● According to DSM-IV-TR criteria set by the American Psychiatric Association, at least 15 percent of men and about 10 percent of women in the U.S. have met the criteria for alcohol dependence at some time in their lives. An estimated 10 percent of adults overall and 6 percent of college students have met the criteria for alcohol dependence during the past year.

physiological Effects of Chronic Alcohol Abuse ● Physical effects of alcoholism include tolerance and

withdrawal, liver disease, cardiovascular disease,

cancer, and neurological disorders such as Wernicke- Korsakoff syndrome.

● A particular concern is the development of fetal alco- hol syndrome (FAS), subsumed under the broader cat- egory, fetal alcohol spectrum disorder (FASD) in the offspring of alcoholic mothers. Despite extensive pre- vention efforts, FASD continues to be the third lead- ing cause of mental retardation not only in the United States but in the entire Western world, exceeded only by Down syndrome and spina bifida.

patterns of Chronic Alcohol Abuse ● Alcoholics can be found in every age, gender, racial,

ethnic, and religious group and in all socioeconomic and geographic categories. Nonetheless, men outnum- ber women in the incidence of alcoholism by about six to one, although women are more vulnerable to alcohol-related organ damage. The elderly tend to be an underreported group with respect to alcoholism.

● A systems approach to alcoholism examines the com- plex interacting relationships among individuals, family, friends, and community. The concept of code- pendency has helped shed light on the specific effects of alcoholism on spouses and other family members. The children of alcoholics (COAs) carry an increased risk of becoming alcoholic as a result of a vulnerability toward alcoholism that is genetically or environmen- tally based, or both.

242 ■ Part Three Legal Drugs in Our Society

The genetics of Alcoholism ● Studies of adoptions and twins have provided informa-

tion about the relative influence of genetics and envi- ronment on the development of alcoholism.

● A distinction has been made between a male or female alcoholic with drinking problems occurring late in life (Type 1) and a male alcoholic with drink- ing problems occurring in adolescence (Type 2). The latter subgroup appears to have a greater genetic com- ponent in the inheritance pattern.

● Recent studies of alcoholism have brought together genetic and environmental factors by identifying two neurochemical systems: the release of corticotrophin- releasing factor (CRF) in the hypothalamus and abnormal glutamate-related activity in brain areas related to substance craving.

The Concept of Alcoholism as a Disease ● The majority position with respect to alcoholism is

that it should be considered a disease and that alco- holics should be treated rather than punished. Since 1957, the American Medical Association has sup- ported this idea.

● Unfortunately, recent surveys of primary care physi- cians indicate that the medical profession is frequently ill prepared to diagnose alcoholism or supervise effec- tive treatment.

Approaches to Treatment for Alcoholism ● Approaches include biologically based treatments and

psychosocial treatments such as the self-help programs of Alcoholics Anonymous (AA).

● Recent biologically based treatments have focused on the reward and craving mechanisms in the brain. Effective treatments include administration of nal- trexone, several types of antiseizure medications, and drugs that affect serotonin activity in the brain.

● Objections to certain aspects of the AA philosophy have promoted the growth of other self-help orga- nizations, such as Moderation Management (MM) and SMART Recovery.

Chronic Alcohol Abuse and Alcoholism in the Workplace ● It has been estimated that about 15 percent of the peo-

ple in the American work force (19.2 million workers) have used alcohol within two hours of reporting to work or during the workday, worked under the influ- ence of alcohol or worked with a hangover at least once in the previous 12 months.

● Corporations and other large organizations have instituted employee assistance programs (EAPs), and unions have instituted member assistance programs (MAPs), to help workers with problems of alcohol abuse or other forms of drug abuse.

Key Terms

abstinence, p. 223 acamprosate, p. 236 alcohol abuse, p. 225 alcohol dependence, p. 225 alcoholic cirrhosis, p. 227 alcoholic dementia, p. 228 alcoholic hepatitis, p. 226 Alcoholics Anonymous

(AA), p. 237 alcoholism, p. 221

alcohol withdrawal syndrome, p. 226

children of alcoholics (COAs), p. 232

codependency, p. 232 concordance rate, p. 233 confabulation, p. 228 delirium tremens (DTs),

p. 226 disulfiram, p. 235

employee assistance programs (EAPs), p. 241

enablers, p. 224 fatty liver, p. 226 fetal alcohol syndrome

(FAS), p. 229 member assistance programs

(MAPs), p. 241 nalmefene, p. 236 naltrexone, p. 236

ondansetron, p. 236 SMART Recovery, p. 240 symptomatic drinking,

p. 221 systems approach, p. 232 teratogenic, p. 229 thiamine, p. 228 Wernicke-Korsakoff

syndrome, p. 228

Endnotes

1. Kinney, J. (2012). Loosening the grip: A handbook of alco- hol information (10th ed.). New York: McGraw-Hill, pp. 40–41 Chapter opening modified from Kinney, p. 216.

2. Kinney, Loosening the grip, pp. 182–185. 3. National Institute on Alcohol Abuse and Alcohol-

ism (2010, April). Rethinking drinking: Alcohol and your health. National Institute on Health Publication 10-3770. Bethesda MD: National Institute on Alcohol Abuse and Alcoholism.

4. Kinney, Loosening the grip, pp. 193–207. 5. Drobes, D. J., and Thomas, S. E. (1999). Assessing craving

for alcohol. Alcohol Research and Health, 23, 179–186. 6. Conner, K. R.; Yue, L.; Meldrum, S.; Duberstein, P. R.;

and Conwell, Y. (2003). The role of drinking in suicidal ideation: Analysis of Project MATCH data. Journal of Studies on Alcohol, 64, 402–408. Schuckit, M. A. (2006). Drug and alcohol abuse: A clinical guide to diagnosis and treatment (6th ed.). New York: Springer, p. 72.

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 243

7. Hussong, A. M.; Bauer, D.; and Chassin, I. (2008). Tele- scoped trajectories from alcohol initiation to disorder in children of alcoholic parents. Journal of Abnormal Psy- chology, 117, 63–78. Maiden, R.P. (1997). Alcohol depen- dence and domestic violence: Incidence and treatment implications. Alcohol Treatment Quarterly, 15, 31–50.

8. National Institute on Alcohol Abuse and Alcoholism (2000, April). Alcohol Alert: Imaging and alcoholism: A window on the brain. No. 47. Rockville, MD: National Institute on Alcohol Abuse and Alcoholism. Schacht, J.P.; Anton, R.F.; Myrick, H. (2013). Functional neuro- imaging studies of alcohol cue reactivity: A quantitative meta-analysis and systematic review. Addiction Biol- ogy,18, 121–133.

9. Fishbein, D.H., and Pease, S.E. (1996). The dynamics of drug abuse. Needham Heights, MA: Allyn and Bacon, pp. 122–124.

10. American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders (4th ed.). Text Revi- sion. Washington, DC: American Psychiatric Associa- tion, pp. 213–214.

11. Grant, B.F.; Stinson, F.S.; Dawson, D.A.; Chou, S.P.; Dufour, M.C.; et al. (2004). Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders. Archives of General Psychiatry, 61, 807–816. Schuckit, Drug and alcohol abuse, pp. 90–91.

12. Edwards, A. C.; Gillespie, N. A.; Aggen, S. H.; and Kendler, K. S. (2013). Assessment of a modified DSM-5 diagnosis of alcohol use disorder in a genetically infor- mative population. Alcoholism: Clinical and Experimen- tal Research, 37, 443–451.

13. Becker, H. (2008). Alcohol dependence, withdrawal, and relapse. Alcohol Research and Health, 31, 348–361. Bayard, M.; Mcintyre, J.; Hill, K.R.; and Woodside, J. (2004). Alcohol withdrawal syndrome. American Family Physician, 69, 1443–1450. Schuckit, Drug and alcohol abuse, pp. 78–80, 88–90.

14. Centers for Disease Control and Prevention (2012, June 6). Deaths: Leading causes for 2008. National Vital Sta- tistics Reports, 60, 1–95, Table D.; Szabo, G., and Man- drekar, P. (2010). Alcohol and the liver. Alcohol Research and Health, 33, 87–96. Brick, J. (2008). Characteristics of alcohol: Definitions, chemistry, measurement, use, and abuse. In J. Brick (Ed.), Handbook of medical conse- quences of alcohol and drug abuse (2nd ed.). New York: Routledge, pp. 27–31.

15. Mukamal, K.J.; Tolstrup, J.S.; Friberg, J.; Jensen, G.; and Gronbaek, M. (2005). Alcohol consumption and risk of atrial fibrillation in men and women. Circulation, 112, 1736–1742.

16. Bagnardi, V.; Blangliardo, M.; and LaVecchia, C. (2001). Alcohol consumption and the risk of cancer: A meta-analysis. Alcohol Research and Health, 25, 263– 270. Molina, P.E.; Happel, K.I.; Zhang, P.; Kolls, J.K.; and Nelson, S. (2010). Alcohol and the immune system. Alcohol Research and Health, 33, 97–108. Singletary, K.W., and Gapstur, S.M. (2001). Alcohol and breast

cancer: Review of epidemiologic and experimental evi- dence and potential mechanisms. Journal of the Ameri- can Medical Association, 286, 2143–2151.

17. National Institute on Alcohol Abuse and Alcoholism (2001, July). Alcohol Alert: Cognitive impairment and recovery from alcoholism. No. 53. Rockville, MD: National Institute on Alcohol Abuse and Alcoholism. Oscar-Berman, M., and Marinkovic, K. (2003). Alcohol- ism and the brain: An overview. Alcohol Research and Health, 27, 125–133.

18. Ambrose, M. L.; Bowden, S.C.; and Whelan, G. (2001). Thiamin treatment and working memory function of alcohol-dependent people: Preliminary findings. Alcohol- ism: Clinical and Experimental Research, 25, 112–116. Cook, C.C. (2000, May–June Supplement). Prevention and treatment of Wernicke-Korsakoff syndrome. Alcohol and Alcoholism, 3, 19–20. Witt, E.D. (1985). Neuroana- tomical consequences of thiamine deficiency: A com- parative analysis. Alcohol and Alcoholism, 20, 201–221.

19. Sokol, R.J.; Delaney-Black, V.; and Nordstrom, B. (2003). Fetal alcohol spectrum disorder. Journal of the American Medical Association, 290, 2996–2999. Thomas, J.; Warren, K.; and Hewitt, B.G. (2010). Fetal alcohol spectrum disorders: From research to policy. Alcohol Research and Health, 33, 118–126. Wetherill, L., and Foroud, T. (2011). Understanding the effects of prenatal alcohol exposure using three-dimensional facial imaging. Alcohol Research and Health, 34, 38–41.

20. Centers for Disease Control and Prevention (2011, December). Fetal alcohol spectrum disorder: Data and statistics. Atlanta, GA: Centers for Disease Control and Prevention.

21. National Institute on Alcohol Abuse and Alcoholism (2000, December). Alcohol Alert: Fetal alcohol exposure and the brain. No. 13. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism. U.S. Department of Health and Human Services (2000). Alcohol and health, pp. 300–322.

22. May, P.A. (1998, April). Lessons learned from early studies of alcohol abuse in pregnancy. Presentation at the Early Studies on Prevention of Alcohol Use in Pregnancy Conference, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD. May, P.A., and Gossage, J.P. (2011). Maternal risk factors for fetal alco- hol spectrum disorders. Alcohol Research and Health, 34, 16–23. National Institute on Alcohol Abuse and Alcohol- ism (2004, July). Alcohol Alert: Alcohol—An important women’s health issue. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism.

23. Carroll, L. (2003, November 4). Alcohol’s toll on fetuses: Even worse than thought. New York Times, pp. F1, F6. Floyd, R.L.; O’Connor, M.J.; Sokol, R.J.; Bertrand, J.; and Cordero, J.F. (2005). Recognition and prevention of fetal alcohol syndrome. Obstetrics and Gynecology, 106, 1059–1064. Substance Abuse and Mental Health Services Administration (2012). Results from the 2011 National Survey on Drug Use and Health: Detailed

244 ■ Part Three Legal Drugs in Our Society

tables. Rockville, MD: Substance Abuse and Mental Health Services Administration, Table 6.76B.

24. Centers for Disease Control and Prevention (2012, January 13). Vital signs: Binge drinking prevalence, frequency, and intensity among adults—United States, 2010. Morbidity and Mortality Weekly Report, 61, 14–19.

25. National Institute on Alcohol Abuse and Alcoholism (1999, December). Alcohol Alert: Are women more vulnerable to alcohol’s effects? No. 46. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism. Substance Abuse and Mental Health Services (2011). Results from the 2010 Survey on Drug Use and Health: Detailed tables, Table 2.46B.

26. Centers for Disease Control and Prevention (2012). Vital signs: Binge drinking prevalence, frequency, and inten- sity among adults—United States, 2010. Morbidity and Mortality Weekly Report, 61, 14–19, Figure 2.

27. Merrick, E.L.; Horgan, C.M.; Hodgkin, D.; Garrick, D.W.; et al. (2008). Unhealthy drinking patterns in older adults: Prevalence and associated characteristics. Journal of the American Geriatrics Society, 56, 214–223.

28. Brody, J.E. (2002, April 2). Hidden plague of alcohol abuse by the elderly. New York Times, p. F7. Substance Abuse and Mental Health Services Administration (2007, January/February). Treatment for older adults: What works best? SAMHSA News, pp. 1–5.

29. Fisher, G.L., and Harrison, T.C. (2008). Substance abuse: Information for school counselors, social workers, therapists, and counselors (4th ed.). Boston: Pearson Education, pp. 199-227. Fields, R. (2010). Drugs in per- spective: Causes, assessment, family, prevention, interven- tion, and treatment (7th ed.). New York: McGraw-Hill, pp. 154–173.

30. Doweiko, H.E. (2012). Concepts of chemical dependency (8th ed.). Belmont, CA: Brooks/Cole, pp. 297–306. Beat- tie, M. (2009). The new codependency: Help and guidance for today’s generation. New York: Simon and Schuster.

31. Fields, pp. 204–233. 32. Hands, M., and Dear, G. (1994). Co-dependency: A

critical review. Drug and alcohol review, 13, 437–445. Hurcom, C.; Copello, A.; and Orford, J. (2000). The family and alcohol: Effects of excessive drinking and conceptualization of spouses over recent decades. Sub- stance Use and Misuse, 35, 473–502.

33. Hall, C.W., and Webster, R.E. (2007). Multiple stressors and adjustment among adult children of alcoholics. Addiction Research and Theory, 15, 425–434. Pearson, M. R.; D’Lima, G. M.; and Kelley, M. L. (2011). Self- regulation as a buffer of the relationship between parental alcohol misuse and alcohol-related outcomes in first-year college students. Addictive Behaviors, 36, 1309–1312.

34. Cloninger, C.R.; Gohman, M.; and Sigvardsson, S. (1981). Inheritance of alcohol abuse: Cross fostering analysis of adopted men. Archives of General Psychiatry, 38, 861–868. Devor, E.J., and Cloninger, C.R. (1989). Genetics of alcoholism. Annual Review of Genetics, 23, 19–36.

35. McGue, M.; Pickens, R.W.; and Svikis, D.S. (1992). Sex and age effects on the inheritance of alcohol problems: A twin study. Journal of Abnormal Psychology, 101, 3–17. Substance Abuse and Mental Health Services Administration (2009, June 18). Fathers’ alcohol use and substance use among adolescents. The NSDUH Report. Rockville, MD: Office of Applied Studies, Substance Abuse and Mental Health Services Administration.

36. Nurnberger, J.I., and Bierut, L.J. (2007, April). Seeking the connections: Alcoholism and our genes. Scientific American, pp. 46–53. Stacy, D.; Clarke, T-K.; and Schumann, G. (2009). The genetics of alcoholism. Current Psychiatry Reports, 11, 364–369.

37. Jellinek, E.M. (1960). The disease concept of alcoholism. New Haven, CT: Hillhouse Press. Vaillant, G.E. (1995). The natural history of alcoholism revisited. Cambridge, MA: Harvard University Press.

38. George, W.H., and Marlatt, G.A. (1983). Alcohol- ism: The evolution of a behavioral perspective. In M. Galanter (Ed.), Recent developments in alcoholism. Vol. 1. New York: Plenum, pp. 105–138.

39. Maltzman, I. (1994). Why alcoholism is a disease. Jour- nal of Psychoactive Drugs, 26, 13–31. National Center on Addiction and Substance Abuse at Columbia Univer- sity (2000, May). Missed opportunity: National survey of primary care physicians and patients on substance abuse. New York: National Center on Addiction and Substance Abuse at Columbia University.

40. Babor, T.F., and Del Boca, F.K. (Eds.) (2003). Treat- ment matching in alcoholism. Cambridge, UK: Cam- bridge University Press. Cutler, R.B., and Fishbain, D.A. (2005). Are alcoholism treatments effective? The Project MATCH data. BMC Public Health, 5, 75. Miller, W.R. (2005). Are alcoholism treatments effective? The Project MATCH data: Response. BMC Public Health, 5, 76.:

41. Banys, P. (1988). The clinical use of disulfiram (Antabuse): A review. Journal of Psychoactive Drugs, 20, 243–261.

42. Anton, R.F.; Myrick, H.; Wright, T.M.; Latham, P.K.; Baros, A.M.; et al. (2011). Gabapentin combined with naltrexone for the treatment of alcohol dependence. American Journal of Psychiatry, 168, 709–717. Fertig, J.B.; Ryan, M.L.; Falk, D.E.; Litten, R.Z.; et al. (2012). A double-blind, placebo-controlled trial assessing the efficacy of levetiracetam extended-release in very heavy drinking alcohol-dependent patients. Alcoholism: Clinical and Experimental Research, doi:10.111/j.1530- 0277.2-11.01716.x. Johnson, B.A.; Rosenthal, N.; Capece, J. A.; Wiegand, F.; Mao, L.; et al. (2007). Topi- ramate for treating alcohol dependence: A randomized controlled trial. Journal of the American Medical Associa- tion, 298, 1641–1651. Scott, L. J.; Figgitt, D. P.; Keam, S. J.; and Waugh, J. (2005). Acamprosate: A review of its use in the maintenance of abstinence in patients with alcohol dependence. CNS Drugs, 19, 445–464. Substance Abuse and Mental Health Services Adminis- tration (2007, May/June). Treating alcohol dependence: Naltrexone advisory. SAMHSA News, p. 14.

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 245

43. Hopson, R.E., and Beaird-Spiller, B. (1995). Why AA works: A psychological analysis of the addictive experi- ence and the efficacy of Alcoholics Anonymous. Alcohol- ism Treatment Quarterly, 12, 1–17. Morgenstern, J.; Bux, D.; LaBouvie, E.; Blanchard, K.A.; and Morgan, T.J. (2002). Examining mechanisms of action in a 12-step treatment: The role of 12-step cognitions. Journal of Studies on Alcohol, 63, 665–672. White, W.H. (1998). Slaying the dragon: The history of addiction treatment and recovery in America. Bloomington, IL: Chestnut Health Systems, pp. 127–177.

44. Forcehimes, A.A. (2004). De Profundis: Spiritual trans- formations in Alcoholics Anonymous. Journal of Clini- cal Psychology/In Session, 60, 503–517. How effective is Alcoholics Anonymous? (2003, December). Harvard Medical Letter, p. 7.

45. Ellis, A., and Velten, E. (1992). When AA doesn’t work for you: Rational steps to quitting alcohol. Fort Lee, NJ: Barricade Press. Kaskutas, L.A. (1996). A road less trav- eled: Choosing the “Women for Sobriety” program. Journal of Drug Issues, 26, 77–94. Schmidt, E. (1996). Rational recovery: Finding an alternative for addiction treatment. Alcoholism Treatment Quarterly, 14, 47–57. SMART Recovery (2004). SMART Recovery handbook. Mentor, OH: SMART Recovery®. Winzelberg, A., and Humphreys, K. (1999). Should patients’ religiosity

influence clinicians’ referral to 12-step self-help groups? Evidence from a study of 3,018 male substance abuse patients. Journal of Consulting and Clinical Psychology, 67, 790–794.

46. Frone, M.R. (2006). Prevalence and distribution of alcohol use and impairment in the workplace: A U.S. national survey. Journal of Studies on Alcohol and Drugs, 67, 147–156. Frone, M.R., and Brown, A.L. (2009). Workplace substance-use norms as predictors of employee substance use and impairment: A survey of U.S. workers. Journal of Studies on Alcohol and Drugs, 71, 526–534.

47. Bachrach, S.B.; Bamberger, P.A.; and McKinney, V.M. (2007). Harassing under the influence: The prevalence of male heavy drinking, the embeddedness of permissive workplace drinking norms, and the gender harassment of female coworkers. Journal of Occupational Health Psychology, 13, 232–250. Substance Abuse and Mental Health Services Administration (2009, April 9). Alcohol treatment: Need, utilization, and barriers. The NSDUH Report. Rockville, MD: Office of Applied Studies, Sub- stance Abuse and Mental Health Services Administration. Osilla, K.C.; Zellmer, S.P.; Larimer, M.E.: Neighbors, C.; and Marlatt, G.A. (2008). A brief intervention for at-risk drinking in an employee assistance program. Journal of Studies on Alcohol and Drugs, 69, 14–20.

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T h e f o l l o w i n g v i e w p o i n t s o n whether alcoholism is a disease represent both sides of this con- troversial issue. Read them with an open mind. You don’t have to come up with the final answer, nor should you necessarily agree with the last argument you read. Many of the ideas in this feature come from the sources listed.

POiNT Alcohol abuse has recently been defined by the National Institute on Alcohol Abuse and Alcohol- ism (NIAAA) as existing when three criteria are met: a preoccu- pation with drinking alcohol, a pattern of compulsive use despite the adverse consequences, and a pattern of relapse to alcohol use. Alcoholics cannot control their drinking; that is their disease. Give a drink to a person who is geneti- cally vulnerable to alcohol, and the consumption of alcohol will make that person an alcoholic, just as a person infected with a type of bacteria might acquire an infectious disease.

COUNTErPOiNT First of all, you’re taking consid- erable liberty with the bacterial infection argument. The research on alcoholism does not show that everyone who acquires the behaviors of alcohol abuse was genetically disposed to it. Con- trolled drinking is attainable for at least some alcoholics. How do you separate the alcoholics who

respond less to genetic factors than to environmental ones, and seem to retain some degree of control over their drinking, from those individuals who do not? Besides, we are not talking about alcohol as some invisible bacteria floating around, waiting to “infect” people without their knowledge. Alcohol- ics become alcoholic because they consume a substance that later on they no longer can handle. At one time in their lives, they chose to have that first drink; no one person or thing made them do it.

POiNT We accept the fact that the alco- holic is responsible for “that first drink,” but we assert that the con- sequences are not voluntary. The alcoholic is powerless over alcohol, not over his or her alcoholism. The situation is similar to a diabetic being in control over whether a treatment of insulin injections should be taken. The alcoholic can seek treatment.

COUNTErPOiNT You can’t have it both ways. Being responsible for the treatment of the disease is not the same as being powerless in the face of alcohol- ism (one of the main assumptions of Alcoholics Anonymous). Even the Supreme Court has trouble wrestling with the issue. In 1988, it ruled that two alcoholics could not be excluded from claiming educational benefits normally accorded to veterans just because

their alcoholism prevented them from applying in the time allowed. The Veterans Administration had refused them, claiming that alco- holism, without physical or mental disorders, is an example of “willful misconduct.”

POiNT Not exactly. The Court ruled that the source of the “willful mis- conduct” was the disease of alco- holism. In doing so, it actually reconfirmed the concept of alco- holism as a disease. The courts typically do not excuse the alco- holic from the consequences of the condition. Instead, they give the person a choice of being punished for his or her offenses or accepting a program of rehabilitation. We cannot go back to the days when drinking too much was considered a moral deficiency.

COUNTErPOiNT If alcoholism is a disease, then it’s a very strange one. It may be in a category all its own.

Critical Thinking Questions for Further Debate 1. Suppose that the evidence were

overwhelming that moderate alcohol int ake was a health- promoting activity and that there were social programs pro- moting moderate alcohol use through society. How would this work and would you envi- sion any unanticipated conse- quences? What would be the

P A r T T h r e e

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Point/Counterpoint III

Should Alcoholism Be Viewed as a Disease?

Chapter 9 Chronic Alcohol Abuse and Alcoholism ■ 247

effect on efforts to prevent and treat alcohol abuse?

2. Suppose you are an alcohol abuser and have attended sev- eral meetings of Alcoholics

Anonymous (AA), to no avail. Programs that permit a moderate but nonzero level of alcohol con- sumption have not worked for you either. What options do you

have, assuming you want to stop drinking? Do you go back to AA?

Point/Counterpoint iV can be found on pages 360–361.

Sources: Holden, C. (1987). Is alcoholism a disease? Science, 238, 1647. Levinthal, C.F. (2003). Point/Counterpoint: Opposing perspectives on issues of drug policy. Boston: Allyn and Bacon, Chapters 5 and 6. Maltzman, I. (1994). Why alcoholism is a disease. Journal of Psychoactive Drugs, 26, 13–31. Miller, N., and Toft, D. (1990). The disease concept of alcoholism and other drug addiction. Center City, MN: Hazelden Foundation.

248

I know the old joke. Mark Twain said that quitting smoking

was easy and that he should know because he had done it

hundreds of times. Well, I should know too. It seems that I’ve

tried to quit hundreds of times too. I realize it’s not good for

me; I’m no fool. But somehow I keep on smoking. My fellow

smokers and I cluster on the sidewalk outside our offices in

the mornings and the afternoons, standing out there in the

rain and the cold. I feel like an outcast of society, day in

and day out. Someday I’ll stop, but in the meantime I will

just have to contend with the disapproving glances, the

inconveniences, the feelings of shame.

—Anonymous

After you have completed this chapter, you should have an understanding of

▶ The story of tobacco through history

▶ The present-day tobacco industry

▶ The main culprits in tobacco smoking: carbon monoxide, tar, and nicotine

▶ Nicotine as a stimulant drug

▶ Nicotine and smoking dependence

▶ Adverse health consequences of smoking

▶ Patterns of tobacco use in the United States

▶ Global issues in the control of tobacco use

▶ Strategies for people who want to stop smoking

Nicotine and Tobacco Use

C h a p t e r

1 0

Chapter 10 Nicotine and Tobacco Use ■ 249

In some ways, our attitudes toward tobacco have not changed very much over the years. In the late sixteenth century, when tobacco was first introduced to the Western world, tobacco smoking for some people was a personally objectionable behavior, yet strangely captivating to those who tried it and enjoyed the experience. The same is true today. And in the twenty-first century, we have as much difficulty quitting as they had in Mark Twain’s time.

In other ways, however, the times have definitely changed. From the 1920s until the mid-1960s, lighting up and smoking a cigarette was an unquestioned sign of sophistication, encouraged by the intense marketing efforts of tobacco manufacturers. Ashtrays and cigarette lighters were standard on automobile dashboards. There was little or no public recognition that harm would come of smoking—a possibility that was concealed for decades by the tobacco industry. It was an era before surgeon general’s reports, Tobacco-Free Kids advertise- ments, National Smoke-Out Days, and smoke-free res- taurants, hotels, and public buildings.

Today, it is no longer a matter of debate that tobacco smoking is a major health hazard, not only to the individual doing the smoking but also to society at large. It is also no longer a matter of debate that the main psychoactive ingredient in tobacco, nicotine, is a major

dependence-producing drug. Even the tobacco compa- nies now concede that their product is dangerous.

Yet at the same time, tobacco products are legally sanctioned commodities with an economic significance, both to the United States and to the world. Banning tobacco products would lead us into a Prohibition era com- parable to or perhaps exceeding in social upheaval the one experienced with respect to alcohol in the last century (see Chapter 8). How did we arrive at this point, and what lies ahead? This chapter will explore what we now know about the effects of tobacco smoking and other forms of tobacco use, the impact these behaviors have had on American society and the world, and the ways in which we have dealt with the issue of tobacco use over the years. It also will con- sider current approaches to helping people who choose to stop smoking, and prevention strategies to encourage young people not to start smoking in the first place.

Tobacco Use through History

Shortly after setting foot on the small island of San Salvador on October 12, 1492, Christopher Columbus received from the inhabitants a welcoming gift of large, green, sweet-smelling tobacco leaves. Never having seen tobacco before, Columbus did not know what to make of this curious offering, except to observe in his journal that the leaves were greatly prized by the “Indians.” In the first week of November, two members of the expedition ventured to the shores of Cuba, searching at Columbus’s insistence for the great khan of Cathay (China). They found no evidence of the khan but did return with reports of natives who apparently were “drinking smoke.”

Before long, Columbus’s men were “tobacco drink- ing” as well. One sailor in particular, Rodrigo de Jerez, became quite fond of the practice. He was, in fact, histo- ry’s first documented European smoker, though he lived to regret it. When Rodrigo returned to Spain, he vol- unteered to demonstrate the newfound custom to his neighbors, who, instead of being impressed, thought that anyone who could emit smoke from the nose and mouth without burning had to be possessed by the Devil. A par- ish priest turned Rodrigo over to the Inquisition, which sentenced him to imprisonment for witchcraft. He spent several years in jail, presumably without a supply of tobacco. Rodrigo therefore also may be remembered as the first European smoker to quit cold turkey.1

In 1559, the year historians mark as the year tobacco was officially introduced to Europe, the French ambas- sador to Portugal, Jean Nicot, presented some tobacco plants acquired in the New World to Catherine de Medici, Queen of France as a possible treatment for her migraine headaches (supposedly it helped); the plant was

by the numbers . . .

>300 million The estimated number of men in China who are regular tobacco smokers, a number exceeding the population of the United States.

5.4 million The estimated number of people worldwide who die each year from tobacco-related lung cancer, heart disease, and other illnesses.

>8 million The estimated number of people worldwide who will die each year by 2030, if present trends continue; 80 percent of these deaths will be in developing nations.

100 million The estimated number of people worldwide in the twentieth century who died prematurely of tobacco- related disease.

Sources: World Health Organization (2010). Tobacco: Key facts. Geneva, Switzerland: World Health Organiza- tion. World Health Organization (2009). WHO report on the global tobacco epidemic 2009. Geneva, Switzerland: World Health Organization. World Health Organization (2008). The WHO report on the global tobacco epidemic 2008. Geneva, Switzerland: World Health Organization.

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named a century later, Nicotiana tabacum, after him. The medical applications, however, quickly became secondary to its recreational use. The practice of smoking tobacco soon became fashionable among European aristocracy.

Not everyone was enthusiastic about this new fad. In 1604, predating a modern-day surgeon general’s report by more than 350 years, King James I of England wrote “A Counter-blaste to Tobacco,” a lengthy trea- tise condemning tobacco use. Referring to tobacco as a “stinking weede,” he characterized smoking as “a cus- tom loathsome to the eye, hateful to the nose, harmful to the brain, [and] dangerous to the lung.” In the first recorded comment on its potential for causing depen- dence, the king observed that “he that taketh tobacco saith he cannot leave it, it doth bewitch him.”

Politics, Economics, and Tobacco Elsewhere in the world, during the early seventeenth century, the condemnation of tobacco became extreme. In Russia, officials established penalties for smoking that included whipping, mutilation, exile to Siberia, and death. Turkey, Japan, and China tried similar tactics, but not surprisingly, tobacco use continued to spread.2

By the end of the seventeenth century even the fiercest opponents of tobacco had to concede that it was here to stay. A sultan of Turkey in 1648 became a smoker himself, and naturally, Turkish penalties for tobacco use vanished overnight; Czar Peter the Great in 1689 pledged to open up Russia to the West, and tobacco sud- denly became a welcome symbol of modernism; Japan and China gave up trying to enforce a prohibition that citizens obviously did not want. Even England’s James I put aside his personal distain for tobacco when he real- ized that a new source of revenue could come from taxes imposed on this popular new commodity.3

Snuffing and Chewing One form of tobacco use observed by the early Spanish explorers was the practice of grinding a mixture of tobacco into a fine powder (snuff), placing or sniffing a pinch of it into the nose, and exhaling it with a sneeze. By the 1700s, this custom, called snuffing, overtook smoking as the dominant European form of tobacco use. Among French

aristocrats, both men and women, expensive snuffs, per- fumed with exotic scents and carried in jeweled and enam- eled boxes, became part of the daily routine at the court in France and then in the rest of Europe. Sneezing was considered to clear the head of “superfluous humours,” invigorate the brain, and brighten the eyes. In an era when bad smells were constant features of daily living, snuffing brought some degree of relief, not to mention a very effec- tive way of sending nicotine to the brain (see Chapter 3).

Because of their dominance in the rapidly expanding tobacco market, the British colony of Virginia in America prospered greatly. England enjoyed a profitable tobacco trade as a result, but you might say that its development of colonial tobacco growing would eventually backfire. In 1777, when Benjamin Franklin was sent as an envoy to France to gain support against the British in the American War for Independence, a key factor in his success was an offer to deliver prime Virginia tobacco in return for French money. The French liked the idea, and the rest is history. Had it not been for American tobacco, there might not have been a United States of America at all.4

In the United States, snuffing was soon replaced by a more rough-and-ready method for using tobacco: chewing. The practice was not totally new; early Spanish explorers had found the natives chewing tobacco as well as smoking it from the earliest days of their conquest, although North American tribes preferred smoking exclu- sively. Chewing tobacco had the advantage of freeing the hands for work, and its low cost made it a democratic custom befitting a vigorous new nation in the nineteenth century. However, the need to spit out tobacco juices on a regular basis raised the tobacco habit to unimaginable heights of gross behavior. It was enough to make the objections to smoke and the hazards of fire fade into insig- nificance; now the problem was a matter of public health. Tobacco spitting became a major factor behind the spread of infectious diseases such as tuberculosis. Adding to this unsavory picture was the fact that a man’s accuracy in tar- geting the nearest spittoon was inevitably compromised by his level of alcohol consumption, which was setting all- time records during this period (see Chapter 8).

Cigars and Cigarettes By the time of the American Civil War, the fashion in tobacco use began to shift once more, as its overall popu- larity continued to soar. Although the plug of tobacco suit- able for chewing was still a major seller and would remain so until the early twentieth century, two new trends emerged, particularly in the growing industrial cities.

The first trend was the popularity of smoking cigars (commonly known as “seegars”), tight rolls of dried

snuff: A quantity of finely shredded or powdered tobacco. Modern forms of snuff are available in either dry or moist forms.

snuffing: The ingestion of snuff either by inhalation or by absorption through tissue in the nose.

cigars: Tightly rolled quantities of dried tobacco leaves.

Chapter 10 Nicotine and Tobacco Use ■ 251

tobacco leaves. New innovations in curing (drying) tobacco leaves had produced a milder and lighter-quality leaf that was more suitable for smoking than the older forms that had been around since the colonial period. North Carolina, with its ideal soil for cultivating this type of tobacco emerged as the tobacco-growing center of the United States; it continues to do so today. With the advent of cigars, tobacco consumers could combine the feeling of chewing (since the cigar remained in the mouth for a relatively long period of time) and the effects of ingesting tobacco smoke. Pioneers heading west could indulge in foot-long cigars called “stogies,” named after the Conestoga wagons that they rode during the long and tedious journey.

The second trend was the introduction of cigarettes, rolls of shredded tobacco wrapped in paper. They had become popular among British soldiers returning from the Crimean War in 1856, who had adopted the practice from the Turks. Europe took to cigarettes immediately, but the United States proved a harder sell. Part of the problem was the opposition of a well-entrenched U.S. cigar indus- try, which did not look kindly on an upstart competitor. Cigar makers did not discourage the circulation of rumors that the cigarette paper wrapping was actually soaked in arsenic or white lead, that cigarette factory workers were urinating on the tobacco to give it an extra “bite,” or that Egyptian brands were mixed with crushed camel dung.5

An even greater marketing challenge than unsub- stantiated rumors was the effeminate image of ciga- rette smoking itself. A cigarette was looked upon as a dainty, sissy version of the he-man cigar; cigars were fat, long, and dark, whereas cigarettes were slender, short, and light. Well into the beginning of the twenti- eth century, this attitude persisted. This is what John L. Sullivan, champion boxer and self-appointed defender of American masculinity, thought of cigarettes in 1904:

Who smokes ‘em? Dudes and college stiffs—fellows who’d be wiped out by a single jab or a quick under- cut. It isn’t natural to smoke cigarettes. An American ought to smoke cigars. . . . It’s the Dutchmen, Italians, Russians, Turks, and Egyptians who smoke cigarettes and they’re no good anyhow.6

The public image of the cigarette eventually would change dramatically; until then, cigarette manufacturers had to rely instead on a powerful marketing advantage: low cost. In 1881, James Bonsack patented a cigarette- making machine that transformed the tobacco indus- try. Instead of producing at most 300 cigarettes an hour by hand, three machine operators could now turn out 200 a minute, or roughly 120,000 cigarettes a day. This is a snail’s pace compared to today’s state-of-the-art machines, which can produce more than 10,000 cigarettes a minute,

but in those days, the Bonsack machine was viewed as an industrial miracle. Cigarettes by the end of the 1800s were as cheap as twenty for a nickel.7

Tobacco in the Twentieth Century At the beginning of the twentieth century, Americans could choose from a variety of ways to satisfy their hunger for tobacco and the psychoactive effects it could bring. Cigars and pipes were still the dominant form of tobacco use, but the future favored the cigarette for two basic rea- sons. First, a growing number of women began to chal- lenge the idea of masculine dominance, and smoking tobacco was one of the privileges of men that women now wanted to share. Not that women smoking was met with immediate acceptance; in one famous case in 1904, a New York City woman was arrested for smoking in

To encourage male cigarette smokers, advertisements drew heavily on an association with baseball players. What is arguably the most famous and most valuable baseball card, depicting 1909 baseball player Honus Wagner, was actually included in a packet of cigarettes, long before baseball cards became associated with bubble gum.

cigarettes: Rolls of shredded tobacco wrapped in paper, today usually fitted at the mouth end with a filter.

252 ■ Part Three Legal Drugs in Our Society

public. Nonetheless, as smoking became more common among women, the mild-tasting, easy-to-hold cigarette was the perfect option for them. By the 1920s, advertising slogans such as “Reach for a Lucky instead of a sweet” (a clever effort to promote cigarette smoking as a weight- control aid) as well as endorsements by glamorous celeb- rities were being designed specifically for the women’s market. The second factor was World War I, during which time cigarettes became logical form of tobacco easily taken along to war. Times of tension have always been times of increased tobacco use. When the war was over, the cigarette was, in the words of one historian, “enshrined forever as the weary soldier’s relief, the wor- ried man’s support, and the relaxing man’s companion.”8

Cigarettes really came into their own in the 1920s, with the introduction of heavily advertised brand names and intense competition among American tobacco com- panies. Cigarette sales in the United States increased from $45 billion in 1920 to $80 billion in 1925 and $180 billion by 1940.9

Health Concerns and Smoking Behavior

A combination of mass-media advertising and the endorsement of smoking by sports celebrities and glam- orous people in the entertainment industry enabled the tobacco industry, now dominated by cigarettes, to increase its volume of sales from the 1940s to the 1980s by a steady 9 billion cigarettes each year. The peak in domestic sales was reached in 1981, when approximately 640 billion were sold. Owing to the increase in popula- tion, however, per capita consumption in the United States had peaked in 1963 at approximately 4,300 ciga- rettes per year (roughly twelve cigarettes per day).

Beginning in 1964, per capita consumption began a steady decline to approximately 1,600 per year (roughly four cigarettes per day). The year of the turnaround coincided with the U.S. surgeon general’s first report on smoking and health. For the first time, the federal

Health Line African Americans, Smoking, and Mentholated Cigarettes

It has long been puzzling that African Americans tend to smoke fewer cigarettes than white smokers but carry a higher risk of tobacco-related disorders such as lung cancer and heart disease. One factor that has been used as an explanation is the relatively slower rate of nicotine metabolism among African Americans following cigarette smoking (Chapter 3). African Americans may be taking in and retaining relatively more nicotine per cigarette and, as a result, may not need to smoke as many cigarettes per day to take in an equivalent dose of nicotine.

Recent studies have indicated that a major factor might be the menthol in certain brands of cigarettes. More than 60 percent of African American smokers prefer mentholated brands such as Newport and Kool over non- mentholated brands such as Marlboro and Camel, almost the complete opposite to the pattern of brand preferences among white smokers. Menthol allows smokers to take in more smoke and possibly hold it in longer, essentially canceling any benefit of choosing a “light” or “ultralight” brand to smoke. Relative to other smokers, African Ameri- cans who smoked menthol cigarettes had higher levels in their saliva of a specific nicotine by-product. The finding that smokers of mentholated cigarettes are almost twice as likely to relapse after attempts to quit smoking, compared to smokers of nonmentholated cigarettes, is consistent with the relatively higher levels of nicotine intake likely to occur when one is smoking mentholated brands.

The growing evidence of the effect of menthol con- tent in cigarettes on smoking behavior and the implica- tions with regard to smoking cessation have led some to demand that tobacco companies be required to report how much menthol is contained in various cigarette brands, as they now do for levels of nicotine and tar. Others have even called for mentholated cigarettes to be banned altogether. These actions might come about as part of future FDA regulations over tobacco products, as authorized by the Tobacco Control Act of 2009.

Sources: Celebucki, C. C.; Wayne, G. F.; Connolly, G. N.; Pankow, J. F.; and Chang, E. I. (2005). Characterization of measured menthol in 48 U.S. cigarette sub-brands. Nicotine and Tobacco Research, 7, 523–531. Mustonen, T. K.; Spencer, S. M.; Hoskinson, R. A.; Sachs, D. P. L.; and Garvey, A. J. (2005). The influence of gender, race, and menthol content on tobacco exposure measures. Nicotine and Tobacco Research, 7, 581–590. Pletcher, J.; Hulley, B. J.; Houston, T.; Kiefe, C.; Benowitz, N.; et al. (2006). Men- thol cigarettes, smoking cessation, atherosclerosis, and pulmonary function. Archives of Internal Medicine, 166, 1915–1922. Samet, J., and Wipfli, H. (2009). Unfinished busi- ness in tobacco control. Journal of the American Medical Association, 302, 681–682. Substance Abuse and Mental Health Services Administration (2009, November 19). Use of menthol cigarettes. The NSDUH Report. Rockville, MD: Sub- stance Abuse and Mental Health Services Administration.

Chapter 10 Nicotine and Tobacco Use ■ 253

government asserted publicly what had been suspected for decades: the link between tobacco smoking and can- cer and other serious diseases. A succession of surgeon general’s reports since 1964 has produced a number of important developments in tobacco use in America.

■ As evidence of health risks accumulated, restrictions on public consumption were instituted. In 1971, all television advertising for tobacco was banned, and in 1984, a rotating series of warning labels (which had been required on all packages of tobacco products since 1966) were required on all print advertisements and outdoor billboards.

■ There was a significant change in the type of cigarette smoked by the average smoker. In the 1950s, more and more cigarette smokers chose to smoke filtered rather than unfiltered cigarettes, in an effort to ingest less of the toxins in tobacco. By the 1990s, about 95 percent of all smokers were using filtered brands. However, after the introduction of filtered cigarettes, the industry changed the formulation of the tobacco to a stronger blend with an increased tar content. As a result of a stronger “filter blend” formula in the cigarette, sidestream smoke, the smoke directly inhaled by a nonsmoker from a burning cigarette, ended up more toxic when originat- ing from a filtered cigarette than it was from an unfil- tered one. In principle, a cigarette filter should have allowed a flow of air through small holes in the filter itself. Because a smoker typically held the cigarette with the fingers covering these holes, however, little or no filtering was accomplished. In the meantime, filtered cigarettes increased tobacco company profits. Filters were only paper and therefore cost considerably less than filling the same space with tobacco.

■ As a consequence of the surgeon general’s assertion that tar and nicotine were specifically responsible for increased health risks from smoking, new “light” and “mild” cigarette brands were introduced that were low in tar and nicotine (T/N), and the Federal Trade Commission began to issue a listing of tar and nicotine levels in major commercial brands. As later surgeon general’s reports indicated, however, smok- ers canceled out the benefits of switching to low T/N brands by varying the manner in which they smoked low-T/N cigarettes. Smokers took more puffs, inhaled more deeply, and smoked more of such cigarettes so as to get the same amount of nicotine (the same number of nicotine “hits”). Moreover, a greater num- ber of low-T/N cigarettes had to be smoked in order to satisfy the smoker’s needs. In 2010, tobacco com- panies were mandated to change the branding labels to acknowledge that “light” and “mild” brands were no less harmful than regular brands. Marlboro Lights

for example, became Marlboro Gold; Marlboro Ultra Lights became Marlboro Silver.

■ In 2007, it was confirmed that cigarette manufacturers had increased the nicotine concentrations in tobacco from 1997 to 2005 by 11 percent and also had modi- fied certain design features of the cigarettes them- selves to increase the number of puffs per cigarette during smoking. In the “medium/mild” market cat- egory, nicotine levels more than doubled from 1998 to 2005 in nonmentholated cigarettes and rose by 22 percent in mentholated cigarettes (Health Line).10

The Tobacco Industry Today

The tobacco industry in the United States, since the early 1990s, has faced continuing challenges from fed- eral governmental agencies, as well as individuals and groups who have sued tobacco companies for damages resulting from the ingestion of their tobacco products. As a result the legal and economic status of the tobacco industry has been altered significantly.

Two major events occurred in the 1990s that would forever change the image of tobacco use in American soci- ety. In 1993, the U.S. Environmental Protection Agency (EPA) announced its conclusion from available research that environmental tobacco smoke (ETS), the side- stream smoke in the air that is inhaled by nonsmokers as a result of tobacco smoking, causes lung cancer. Since then, most U.S. states, cities, and communities have enacted laws mandating smoke-free environments in all public and private workplaces, unless ventilated smoking rooms have been provided. It is now commonplace for restaurants, hotels, and other commercial spaces to be completely smoke-free. In 1994, congressional hearings were held on allegations that during the 1970s tobacco companies had suppressed data obtained in their own research laborato- ries regarding the hazards of cigarette smoking. In 1999, the Philip Morris company issued a statement, formally admitting that there is “overwhelming medical and scien- tific consensus that cigarette smoking causes cancer, heart disease, emphysema, and other serious diseases in smok- ers” and that “cigarette smoking is addictive, as that term is most commonly used today.” This stance represented a complete reversal of the industry’s 1994 congressional

sidestream smoke: Tobacco smoke that is inhaled by nonsmokers from the burning cigarettes of nearby smokers. Also referred to as environmental tobacco smoke. environmental tobacco smoke (ETS): Tobacco smoke in the atmosphere as a result of burning cigarettes; also called sidestream or secondary smoke.

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testimony regarding tobacco use and continues to be a part of the company’s official web site.11

The Tobacco Settlement of 1998 The major American tobacco corporations entered into an agreement with all fifty U.S. states in 1998 to resolve claims that the states should be compensated for the costs of treating people with smoking-related illnesses. Under the terms of the settlement, the tobacco industry agreed to pay the states approximately $246 billion in annual installments over twenty-four years. The tobacco industry also agreed to refrain from marketing tobacco products to those under eighteen and to pay $24 mil- lion annually over ten years for a research foundation dedicated to finding ways to reduce smoking among youths. In contrast to earlier proposed settlements, how- ever, tobacco corporations under this agreement would not be penalized if levels of underage smoking did not decline over that period of time. In addition, the settle- ment did not prevent individuals or groups of individu- als from suing tobacco corporations in separate actions.

Unfortunately, the 1998 tobacco settlement had only a mixed effect on American smokers. On the one hand, an increase in cigarette prices imposed by tobacco com- panies to finance the costs of the settlement, as well as an increase in excise taxes imposed by U.S. states, made cigarettes more expensive, especially for young people with relatively little money to spend. The decline in cigarette smoking in this age group since 1998 has been attributed, in part, to the economics of tobacco product purchases. On the other hand, however, compensa- tion funds awarded to the states were eventually used to keep taxes down or pay off debt, rather than supporting programs designed to discourage tobacco use. In 2011,

only two states (Alaska and North Dakota) had directed settlement revenue toward prevention programs at the minimum levels recommended by the U.S. Centers for Disease Control and Prevention, and four other states (Delaware, Hawaii, Maine, and Wyoming) had provided only half the recommended funding. Overall, less than two percent of the revenue collected by the states were used for the purposes envisioned by the settlement.12

The Tobacco Control Act of 2009 In June 2009, a new era in the history of governmental relations with the tobacco industry began with the enact- ment of the federal Family Smoking Prevention and Tobacco Control Act, giving the FDA for the first time sweeping regulatory authority over tobacco products sold in the United States. The immediate effects of the legisla- tion included creation of a new FDA Center for Tobacco Products to oversee the science-based regulation of tobacco products, the banning of candy-flavored cigarettes, full dis- closure of ingredients and additives in tobacco products, aggressive moves to stop youth-focused marketing, and new graphic warning labels highlighting the health risks of smoking. In addition, no tobacco product that has been changed since 2007 can be sold without FDA review.13

Tobacco Regulation and Global Economics As will be discussed later in this chapter, many other nations have substantially higher prevalence rates for cigarette smoking, and their governments have taken far fewer steps toward instituting policies to reduce smok- ing behavior. For American tobacco corporations, an expanding global marketplace for American cigarettes has given them the opportunity for an increase in prof- its from foreign sales that has largely compensated for the financial losses from a decline in domestic sales. In a larger sense, cigarette sales abroad today repre- sent a major component of overall U.S. foreign trade. In recent years, U.S. exports of tobacco products have exceeded imports by billions of dollars, creating a sig- nificant trade surplus. Therefore, the U.S. trade deficit (defined as an excess of imports over exports) would be considerably worse than it is today were it not for the export of American tobacco products to other nations.14

What’s in Tobacco?

When a smoker inhales from a lit cigarette, the temperature at the tip rises to approximately 1,700 degrees Fahrenheit (926 degrees centigrade), as oxygen is drawn through the

In 1994, tobacco industry executives testified before a congressional committee in defense of cigarette smoking and other tobacco use. In 1999, the Philip Morris company formally reversed its earlier position that smoking was not addictive.

Chapter 10 Nicotine and Tobacco Use ■ 255

tobacco, paper, and other additives. This accounts for the bright glow as a smoker inhales from a cigarette. At this intense heat, more than four thousand separate com- pounds are oxidized and released through cigarette smoke. The smoker inhales the result as mainstream smoke, usually screened through the cigarette filter and cigarette paper. As mentioned earlier, the sidestream smoke that is released from the burning cigarette tip itself is unfiltered, and because it is a product of a slightly less intense burn- ing process occurring between puffs, more unburned particles are contained in the smoke.

In general, we can speak of two components in tobacco smoke. The particulate phase, consisting of small particles (one micrometer or larger in diameter) suspended in the smoke, includes water droplets, nico- tine, and a collection of compounds that will be referred to collectively as tar. The particles in tar constitute the primary source of carcinogenic compounds in tobacco. The second component is the gaseous phase, consisting of gas compounds in the smoke, including carbon diox- ide, carbon monoxide, ammonia, hydrogen cyanide, acetaldehyde, and acetone. Among these gases, carbon monoxide is clearly the most toxic.

This diverse collection of physiologically active toxins is quite unique to tobacco. One way of putting it is to say that the fifty thousand to seventy thousand puffs per year that a one-pack-a-day cigarette smoker takes in amount to a level of pollution far beyond even the most polluted urban environment anywhere in the world.15 The following sec- tions will focus on three of the most important compounds in tobacco smoke: carbon monoxide, tar, and nicotine.

Carbon Monoxide Carbon monoxide is an odorless, colorless, tasteless, but extraordinarily toxic gas. It is formed when tobacco burns because the oxidation process is incomplete. In that sense, burning tobacco is similar to an inefficient engine, like a car in need of a tune-up. The danger in carbon monoxide is that it easily attaches itself to hemo- globin, the protein inside red blood cells, occupying those portions of the hemoglobin molecule normally reserved for the transport of oxygen from the lungs to the rest of the body. Carbon monoxide has about a two hundred times greater affinity for hemoglobin than does oxygen, so oxygen does not have much of a chance. Carbon monoxide is also more resistant to detaching itself from hemoglobin, so there is an accumulation of carbon monoxide over time.

The ultimate result of carbon monoxide is a subtle but effective asphyxiation of the body from a lack of oxygen. Generally, people who smoke a pack a day accumulate levels of carbon monoxide in the blood of

25 to 35 parts per million blood components (p.p.m.), with levels of 100 p.p.m. for short periods of time while they are actually smoking. Of course, greater use of tobacco produces proportionately higher levels of carbon monoxide. Carbon monoxide is the primary culprit in producing cardiovascular disease among smokers, as well as in causing deficiencies in physi- ological functioning and behavior.16

Tar The quantity of tar in a cigarette varies from levels of 12 to 16 mg per cigarette to less than 6 mg. It also should be noted that the last third of each cigarette con- tains 50 percent of the total tar, making the final few puffs far more hazardous than the first ones.

The major problem with tar lies in its sticky qual- ity, not unlike that of the material used in paving roads, which causes it to adhere to cells in the lungs and the airways leading to them. Normally, special- ized cells with small, hair-like attachments called cilia are capable of removing contaminants in the air that might impede the breathing process. These cilia liter- ally sweep the unwanted particles upward, in a process called the ciliary escalator, to the throat, where they are typically swallowed, digested, and finally excreted from the body through the gastrointestinal system. Components in tar alter the coordination of these cilia so that they can no longer function effectively. The accumulation of sticky tar on the surface of the cells along the pulmonary system permits carcinogenic com- pounds that normally would have been eliminated to settle on the tissue. As will be discussed later, the result- ing cellular changes produce lung cancer, and similar carcinogenic effects in other tissues of the body pro- duce cancer in other organs.17

mainstream smoke: The smoke inhaled directly from cigarettes or other tobacco products.

particulate phase: Those components of smoke that consist of particles.

tar: A sticky material found in the particulate phase of tobacco smoke and other pollutants in the air.

gaseous phase: The portion of tobacco smoke that consists of gases.

carbon monoxide: An extremely toxic gas that prevents blood cells from carrying oxygen from the lungs to the rest of the body.

cilia: Small hair cells. ciliary escalator: The pushing of inhaled foreign particles, which might interfere with breathing, upward from the air passages into the throat, where they can be swallowed and excreted through the gastrointestinal tract.

256 ■ Part Three Legal Drugs in Our Society

Nicotine Nicotine is a toxic, dependence-producing psycho- active drug found exclusively in tobacco. It is an oily compound varying in hue from colorless to brown. A few drops of pure nicotine, about 60 mg, on the tongue would quickly kill a healthy adult, and it is commonly used as a major ingredient in insecticides and pesti- cides of all kinds. Cigarettes, however, contain from 0.5 to 2.0 mg of nicotine (depending on the brand), about 20 percent of which is actually inhaled and reaches the bloodstream. This means that 2 to 8 mg of nicotine is ingested per day for a pack-a-day smoker, and 4 to 16 mg of nicotine for a smoker of two packs a day.18

Inhaled nicotine from smoking is absorbed extremely rapidly and easily passes through the blood– brain barrier, as well as through the blood–placenta bar- rier in pregnant women, in a few seconds. The entire effect is over in a matter of minutes. By the time a ciga- rette butt is extinguished, the levels of nicotine in the blood have peaked, and its breakdown and excretion from the body are well under way. The elimination half- life of nicotine is approximately two to three hours.

The speed of nicotine absorption ordinarily would be much slower if it were not for the presence of ammo- nia as an additive in the tobacco blend. The combination of nicotine and ammonia changes the naturally acidic nicotine into an alkalinic free-base form that more easily passes from body tissues into the bloodstream. As a result, ammonia increases the availability of nicotine in the blood, much as the addition of alkaline materials such as baking soda converts cocaine into crack cocaine (see Chapter 4). The information that ammonia had been introduced into the manufacture of cigarette tobacco dur- ing the 1970s, in an apparent effort to increase the “kick” of nicotine, came to light in 1995 and was confirmed by tobacco industry documents released in 1998.19

The primary effect of nicotine is to stimulate CNS receptors that are sensitive to acetylcholine (see Chapter 3). These receptors are called nicotinic recep- tors because they are excited by nicotine. One of the effects of activating them is the release of adrenalin, which increases blood pressure and heart rate. Another effect is to inhibit activity in the gastrointestinal system. At the same time, however, as most smokers will tell you, a cigarette is a relaxing factor in their lives. Part of this

reaction may be due to an effect on the brain that pro- motes a greater level of clear thinking and concentration; another part may be related to the fact that nicotine, at moderate doses, serves to reduce muscle tone so that muscular tightness is decreased. Research has shown that cigarette smoking helps to sustain performance on monotonous tasks and to improve short-term memory. We can assume that it is the nicotine in cigarettes and other tobacco products that is responsible, because nico- tine tablets have comparable behavioral effects.20

The Dependence Potential of Nicotine

Historically, the dependence potential of nicotine has been demonstrated at times in which the usual availabil- ity of tobacco has suddenly been curtailed. In Germany following the end of World War II, for example, cigarettes were rationed to two packs a month for men and one pack a month for women. This “cigarette famine” pro- duced dramatic effects on the behavior of German civil- ians. Smokers bartered their food rations for cigarettes, even under the extreme circumstances of chronic hunger and poor nutrition. Cigarette butts were picked from the dirt in the streets by people who admitted that they were personally disgusted by their desperate behavior.21

It is now known that nicotine stimulates the release of dopamine in the nucleus accumbens, the same area of the brain responsible for the reinforcing properties of opi- oids, cocaine, and alcohol. In addition, several behavioral factors combine with this physiological effect to increase the likelihood that a strong dependence will develop. One of these factors is the speed with which smoked nic- otine reaches the brain. The delivery time has been esti- mated as five to eight seconds. Another factor is the wide variety of circumstances and settings surrounding the act of smoking that later come to serve as learned rewards. A smoker may find, for example, that the first cigarette with a cup of coffee in the morning (a source of another psychoactive drug, caffeine) is strongly reinforcing.22

The Titration Hypothesis of Nicotine Dependence The idea that smokers adjust their smoking behavior to obtain a stable dose of nicotine from whatever cig- arettes they are smoking has been called the titration hypothesis. In one study, smokers, when exposed to cig- arettes of decreasing nicotine content, smoked a greater number of them to compensate and increase the vol- ume of each puff. When they inhaled more puffs per

nicotine: The prime psychoactive drug in tobacco products.

titration hypothesis: The idea that smokers will adjust their smoking of cigarettes in such a way as to maintain a steady input of nicotine into the body.

Chapter 10 Nicotine and Tobacco Use ■ 257

cigarette, a greater interval of time elapsed before they lit up another one. If they were given nicotine gum to chew, the intensity of their smoking behavior declined, even though they had not been told whether the gum contained nicotine or is a placebo. Other studies, how- ever, have shown results that are less clear. The current view about the titration hypothesis is that smokers show a partial compensation when switching from higher to lower yields of nicotine. The compensation is greater when switching from lower yields to higher ones.23

Tolerance and Withdrawal First-time smokers often react to a cigarette with a mix- ture of nausea, dizziness, and vomiting. These effects typically disappear as tolerance develops in the nicotinic receptors in the brain. Other physiological effects, such as increases in heart rate, tremors, and changes in skin temperature, show weaker tolerance effects or none at all.

The strongest dependence-related effect of cigarette smoking can be seen in the symptoms of withdrawal that follow the discontinuation of smoking. Within about six hours after the last cigarette, a smoker’s heart rate and blood pressure decrease. Over the next twenty-four hours, common symptoms include headache, an inability to concentrate, irritability, drowsiness, and fatigue, as well as insomnia and other sleep disturbances. Most striking of all are the strong feelings of craving for a cigarette. Ex-smokers can attest to cravings that slowly diminish but nonetheless linger on for months and, in some cases, for years.24

Nicotine dependence is the central factor in the continuation of smoking behaviors. The level of depen- dence is significant, even when compared with depen- dence levels of illicit drugs available on the street. In a study of people who smoked and were also in some form of drug-abuse treatment, 74 percent judged the difficulty of quitting smoking to be at least as great as the difficulty in stopping their drug of choice. One in three considered it “much harder” to quit smoking.25

Health Consequences of Tobacco Use

The adverse health consequences of tobacco use can be classified in three broad categories: cardiovascular disease, respiratory disease, and cancer. In addition, there are spe- cial health problems for women as well as specific hazards from using smokeless tobacco. An enormous literature on the adverse effects of tobacco use has grown steadily since the original surgeon general’s report in 1964, although even by that time more than thirty thousand research stud- ies had been conducted on the question.

Beyond all the research reports are the sheer num- bers of people who are affected. In the United States alone, of the estimated half-million deaths each year that are attributed to substance abuse of one kind or another, approximately 443,000 are specifically tied to tobacco use or to second-hand smoke from tobacco use. This figure is higher than the total number of American casualties dur- ing World War II (Health Line). The public health com- munity considers these deaths premature deaths because they were entirely preventable; these people would have been alive if their behaviors had been different.

The numbers are simple, and staggering: Smoking- related deaths account for nearly one out of every five deaths in the United States every year, more than 1,200 deaths each day. It has been estimated that a per- son’s life expectancy is shortened by fourteen minutes every time she or he smokes a cigarette. Smoking two packs a day for twenty years reduces one’s estimated lifespan by approximately eight years. Unlike alcohol, which presents no significant health hazards when con- sumed in moderation, tobacco is a dangerous product when used as intended (Figure 10.1).26

Cardiovascular Disease Cardiovascular disease includes a number of specific conditions. Some of these diseases are coronary heart disease (CHD), in which the heart is damaged by the

Health Line Visualizing 400,000 to 440,000

Annual Tobacco-Related Deaths

The estimated annual death toll due to tobacco-related diseases is staggering but often difficult to visualize. In 2010, the following U.S. cities had populations in the neighborhood of this number. Imagine the disappear- ance of the entire population in any of these cities each year, or all of them in five years.

• Virginia Beach, Virginia (pop. 437,575) • Atlanta, Georgia (pop. 420,003) • Colorado Springs, Colorado (pop. 416,427) • Omaha, Nebraska (pop. 408,958) • Raleigh, North Carolina (pop. 403,892)

Source: United States Census Bureau, 2010 Census Data.

coronary heart disease (CHD): Disease that damages the heart as a result of a restriction of blood flow through coronary arteries.

258 ■ Part Three Legal Drugs in Our Society

restriction of blood flow through narrowed or blocked coronary arteries; arteriosclerosis, in which the walls of arteries harden and lose their elasticity; atherosclerosis, in which fatty deposits inside arteries impede blood flow; and ischemic stroke, in which interruption or reduc- tion in blood flow causes damage to the brain. In all

these diseases, cigarette smoking increases the risk dramatically.

We know now that smoking is responsible for approxi- mately 30 percent of all CHD deaths. The risk of CHD doubles if you smoke and quadruples if you smoke heavily. On average, smoking also raises the risk of a sudden death (such as from a fatal heart attack) by two to four times, with the degree of risk increasing as a direct function of how many cigarettes are smoked per day. To put it even more bluntly, it has been estimated that unless smoking patterns change dramatically in the future, about 10 percent of all Americans now alive may die prematurely from some form of heart disease as a result of their smoking behavior.27

These statistics are strengthened by our understand- ing of how cigarette smoking actually produces these dangerous cardiovascular conditions. The major villains are nicotine and carbon monoxide. Nicotine, as a stim- ulant drug, increases the contraction of heart muscle and elevates heart rate.

At the same time, nicotine causes the constriction of blood vessels, leading to a rise in blood pressure, and also increases platelet adhesiveness in the blood. As a result of a greater adhesiveness, platelets clump together and increase the risk of developing a blood clot. When a clot forms within coronary arteries, a heart attack can occur; a clot traveling into the blood vessels of the brain can produce a stroke. Finally, nicotine increases the body’s serum cholesterol and fatty deposits, leading to the development of atherosclerosis.

While nicotine is doing its dirty work, carbon mon- oxide makes matters worse. A lack of oxygen puts fur- ther strain on the ability of the heart to function under already trying circumstances.28

Respiratory Diseases The general term chronic obstructive pulmonary disease (COPD) refers to several conditions in which breathing is impaired because of some abnormality in the air passages either leading to or within the lungs. Although only 20 percent of smokers in the United States develop COPD, 80 to 90 percent of all COPD cases are the result of smoking. Historically, COPD has been viewed as “a man’s disease,” but since 1980 the death rate in women has tripled, and since 2000, more women than men have died or been hospitalized each year as a result of COPD. With the exception of a rare genetic defect, smoking is the only established cause of clinically significant COPD.

Two examples of COPD are chronic bronchitis, in which excess mucus builds up in air passages, leading to an inflammation of bronchial tissue, and emphysema,

Lung cancer

126,000 Coronary

heart disease

Stroke

Other diagnoses

Chronic lung disease

Other cancers

15, 900

35,300

128,900

92,900

44,000

F i g u r E 1 0 . 1

The distribution of approximately 443,000 U.S. deaths attributed each year to tobacco use or secondhand smoke from tobacco use.

Source: Centers for Disease Control and Prevention (2008, November 14). Cigarette smoking–attributable morbidity, years of potential life lost, and productivity losses—United States, 2000–2004. Morbidity and Mortality Weekly Report, 57, 1226–1228.

arteriosclerosis (ar-TEEr-ee-oh-scluh-rOH-sis): A disease in which blood flow is restricted because the walls of arteries harden and lose their elasticity.

atherosclerosis (ATH-er-oh-scluh-rOH-sis): A disease in which blood flow is restricted because of the buildup of fatty deposits inside arteries.

ischemic (iz-SKEE-mic) stroke: A disease in which there is an interruption of or reduction in blood flow to the brain, causing paralysis, sensory loss, cognitive deficits, or a combination of neuropsychological effects.

chronic obstructive pulmonary disease (COPD): A group of diseases characterized by impaired breathing due to an abnormality in the air passages.

chronic bronchitis: A respiratory disease involving inflammation of bronchial tissue following a buildup of excess mucus in air passages.

emphysema (EM-fuh-SEE-mah): An enlargement of air sacs in the lungs and abnormalities in the air sac walls, causing great difficulty in breathing.

Chapter 10 Nicotine and Tobacco Use ■ 259

in which air sacs in the lungs are abnormally enlarged and the air sac walls either become inelastic or rup- ture, leading to extreme difficulty in inhaling oxygen and exhaling carbon dioxide. In the case of advanced emphysema, more than 80 percent of a patient’s energy is required merely to breathe. These two diseases account for more than one hundred thousand deaths each year, and many additional thousands are forced to lead increasingly debilitating lives, gasping and strug- gling each day to breathe.

Pulmonary damage, however, is not limited to adults who have been smoking for many years. Cigarette smoking is also associated with airway obstruction and slower growth of lung function in younger popula- tions. Adolescents who smoke five or more cigarettes a day are 40 percent more likely to develop asthma and 30 percent more likely to have symptoms of wheezing but not asthma than those who do not smoke. Among smokers, girls show a greater loss of pulmonary func- tion than boys, even though boys report that they smoke more cigarettes.29

Lung Cancer It is hard to believe that at the beginning of the twen- tieth century, lung cancer was a rare disease. Its steady increase in the United States as well as the rest of the world since then has occurred in direct proportion to the growing prevalence of cigarette smoking and other tobacco use. About 80 percent of an estimated 226,000 new cases of lung cancer in the United States in 2012 have been determined by the American Cancer Society to be smoking-related. Male smok- ers, in particular, are 23 times more likely to develop lung cancer than lifelong nonsmokers. Although there has been a steady decline in deaths due to lung can- cer among American males overall since 1990, there remains an approximately 35 percent greater mortality rate among African American males due to smoking than among white males.

Another important change has occurred over the years with respect to the incidence of lung can- cer among women. Like COPD, lung cancer was once considered to be limited largely to male smok- ers. More recently, however, increasing numbers of women have contracted lung cancer as a result of their increased level of cigarette smoking. The age- adjusted mortality rate for women is still about one- half that for men, and the decline in mortality rates seen among men since 1990 is only beginning to be realized among women. Since 1988, lung cancer has exceeded breast cancer as the leading cause of

cancer deaths among women (Figure 10.2). In gen- eral, females who are currently smoking incur a risk of lung cancer that is about thirteen times higher than that for nonsmokers.

As discussed earlier in the chapter, the exposure to tar in cigarette smoke disrupts the indispensable action of ciliary cells in the bronchial tubes leading to the lungs. Without their protective function, the lungs are open to attack. Several carcinogenic compounds in the smoke can now enter the lungs and stimulate the formation of cancerous growths, carcinomas, in lung tissue. One of these compounds, benzopyrene, has been found to cause genetic mutations in cells that are iden- tical to the mutations observed in patients who have developed carcinomas in their lungs. This finding is important because it establishes a causal link between a specific ingredient in tobacco smoke and human cases of cancer.30

Other Cancers Certainly lung cancer is the best-known and most com- mon example of smoking-related cancers, but other organs are affected in a similar way. In the United States, approximately 30 percent of cancer deaths of all types have been linked to smoking. It has been esti- mated that smokers increase their risk by two to twenty- seven times for cancer of the larynx, thirteen times for mouth or lip cancer, two to three times for bladder can- cer, two times for pancreatic cancer, and five times for cancers of the kidney or uterine cervix.31

Despite a widespread belief to the contrary, using smokeless tobacco, in the form of chewing tobacco or snuff, does not prevent the user from incurring an increased risk of cancer. Continuing contact with tobacco in the mouth has been shown to produce pre- cancerous cell changes, as revealed by leukoplakia (white spots) and erythroplakia (red spots) inside the mouth and nasal cavity. Even though smokeless tobacco obvi- ously avoids the problems associated with tobacco smoke, it does not prevent the user from being exposed to carcinogens, specifically a class of compounds called

carcinomas (CAr-sih-NOH-mas): Cancerous tumors or growths.

leukoplakia (LOO-koh-PLAY-kee-ah): Small white spots inside the mouth and nasal cavity, indicating precancerous tissue.

erythroplakia (eh-riTH-ro-PLAY-kee-ah): Small red spots inside the mouth and nasal cavity, indicating precancerous tissue.

260 ■ Part Three Legal Drugs in Our Society

nitrosamines that are present in all tobacco products. As a result of federal legislation enacted in 1986, all forms of smokeless tobacco must contain, on the package, a set of specific warnings that these products may cause mouth cancer as well as gum disease and tooth loss (Health Alert). To reinforce the idea that grave dangers lurk in smokeless tobacco, one of these warnings reads, “This product is not a safe alternative to cigarette smoking.”

Special Health Concerns for Women Tobacco use presents specific health risks for women. Women who smoke have a more than three times greater risk of dying from stroke due to brain hemorrhaging and an almost two times greater risk of dying from a heart attack. Added to these concerns is the toxic interaction of tobacco smoke with birth control pills. If a woman

is using birth control pills as well, the risk increases to twenty-two times and twenty times, respectively.

The higher risk of low birth weight and physical defects in the newborn due to the mother’s smoking dur- ing pregnancy was discussed in Chapter 2. In addition, there is a specific elevation in systolic blood pressure at about 2 months of age among infants whose moth- ers smoked during pregnancy.32 Even though there has been a decline in smoking in recent years among preg- nant women, more than one in six pregnant women (17 percent) have smoked in the past month, with more of them smoking in their first trimester of pregnancy (22 percent) than in their second and third trimesters (14 percent and 15 percent, respectively).

The Hazards of Environmental Smoke In the early days of development of methods for detecting the effects of nicotine in the bloodstream, scientists were puzzled to find traces of a nicotine

nitrosamines (nih-TrAW-seh-meens): A group of carcinogenic compounds found in tobacco.

100

80

60

40

20

0

R at

e p

er 1

0 0

,0 0

0 p

o p

u la

ti o

n

19 35

19 40

19 45

19 50

19 55

19 60

19 65

19 70

19 75

19 80

19 85

19 90

19 95

20 00

20 05

20 09

19 30

Age-adjusted Cancer Death Rates*, Males and females by site, US, 1930–2009

*Per 100,000, age adjusted to the 2000 US standard population.

Lung and bronchus cancer for males

Lung and bronchus cancer for females

Prostate cancer for males

Breast cancer for females

F i g u r E 1 0 . 2

Age-adjusted death rates from lung and bronchus cancer and other cancers among males and females in the United States, 1930–2009.

Note: Since about 1990, lung and bronchus cancer deaths among women have exceeded breast cancer deaths. In addition, lung and bronchus cancer rates for women have remained relatively stable while rates for men have declined significantly.

Source: American Cancer Society (2013). Cancer Facts and Figures 2013. Atlanta: American Cancer Society, Inc., pp. 2–3.

Chapter 10 Nicotine and Tobacco Use ■ 261

metabolite in nonsmokers. They suspected at first that there was some flaw in their analysis but later had to conclude that their measurements were indeed accurate. Nonsmokers testing positive had shared car rides or workplaces with smokers shortly before their tests. Today, a large body of evidence indicates not only the presence of tobacco smoke compounds in the bodies of nonsmokers but also the adverse con- sequences that such “involuntary smoking” can pro- voke. In other words, environmental tobacco smoke is a significant health hazard even to people who are not actively smoking.

Approximately 85 percent of the smoke in an aver- age room where people are smoking cigarettes is gener- ated by sidestream smoke, and about three-fourths of the nicotine originating from these cigarettes ends up in the atmosphere. In some cases, the carcinogens released in environmental tobacco smoke (ETS) are so potent that they are dangerous even in their diluted state. For exam- ple, N-nitrosamine (an example of a group of carcino- gens mentioned earlier in connection with smokeless tobacco) is so much more concentrated in sidestream

smoke than in mainstream smoke that nonsmokers end up inhaling as much of it after one hour in a very smoky room as will a smoker after smoking ten to fifteen cigarettes.33

The U.S. surgeon general’s report on involuntary exposure to tobacco smoke in 2006 has confirmed previ- ous data on this question and extended its conclusions to the following:

■ For nonsmoking adults, exposure to environmental smoke raises the risk of heart disease by 25 to 30 per- cent in both men and women. The risk of lung cancer is increased by 20 to 30 percent among nonsmokers who live with a smoker.

■ Environmental smoke is a cause of sudden infant death syndrome (SIDS), accounting for 430 deaths per year in the United States. The risk is higher for children whose mothers were exposed to tobacco smoke during pregnancy and for children exposed during infancy.

■ Among children of parents who smoke in the home, there is an increased risk of lower respiratory illnesses such as bronchitis, middle ear disease, wheezing, and childhood asthma.

It is estimated that environmental smoke exposure accounts for 46,000 premature deaths from heart dis- ease and 3,400 premature deaths from cancer among adults in the United States each year. Although the proportion of nonsmokers has declined substantially as a result of publicity about the hazards of ETS and exten- sive smoking bans and restrictions, more than 126 mil- lion Americans remain subject to exposure at some time in their lives.34

Patterns of Smoking Behavior and Use of Smokeless Tobacco

In 1965, about 40 percent of all American teenagers and adults smoked cigarettes, and it is estimated that more than 50 percent did in the 1940s. In 2011, how- ever, according to the National Survey on Drug Use and Health, approximately 22 percent of people aged twelve or older smoked a cigarette within the past month, qualifying as current smokers. Although this percentage is significantly less than it was, it still rep- resents a very large number of people. Extrapolating to the U.S. population, a 22 percent prevalence rate corresponds to about 57 million Americans. American Indians and Alaska natives are more likely to smoke

H E A L T H A L E r T !

Signs of Trouble from Smokeless Tobacco • Lumps in the jaw or neck area • Color changes or lumps inside the lips • White, smooth, or scaly patches in the mouth or on

the neck, lips, or tongue • A red spot or sore on the lips or gums or inside the

mouth that does not heal in two weeks • Repeated bleeding in the mouth • Difficulty or abnormality in speaking or swallowing

Any of these signs should be reported to a physician as soon as possible. In the meantime, and in the future, use of smokeless tobacco should be discontinued.

Where to go for assistance: www.quitnet.com

This web site is sponsored by the Department of Public Health, Boston University.

Source: Payne, W. A; Hahn D. B; and Lucas, E. B. (2009). Understanding your health (10th ed.) New York: McGraw-Hill, p. 279.

262 ■ Part Three Legal Drugs in Our Society

than any other group in the United States, with 37 per- cent of adults defined as smokers. In contrast, individu- als of Asian descent are the least likely to smoke; just 12 percent of them report having smoked a cigarette in the past month.

There has been only a small decline in the per- centage of American adult smokers in the last few years. Among college students, thirty-day prevalence rates increased from 1990 to 1999, but since then they have declined by 50 percent. In 2011, about 15 per- cent of college students had smoked cigarettes within the previous month, considerably below the national average. In 2011, about 12 percent of tenth graders and 19 percent of high school seniors reported ciga- rette smoking within the previous month. Compared to peak levels reached in 1996, these figures represent a 61 percent decline for tenth graders and 49 percent decline for seniors. It is generally considered that if high school seniors have not begun smoking at this point in their lives, it is unlikely that they will do so in the future.35

The Youngest Smokers In the 2011 University of Michigan survey, approxi- mately 18 percent of eighth graders reported that they had tried cigarettes in their lifetime, and about 6 per- cent reported smoking at least once in the previous

month. These figures are down substantially from the 49 and 21 percent figures, respectively, reported in 1996. Approximately 2 percent of eighth grad- ers smoked on a daily basis in 2011, and less than 1 percent smoked at least half a pack a day, once again down substantially from 10 and 4 percent, respec- tively, in 1996.

The peak year for starting to smoke has been reported to be in the seventh grade, although a signifi- cant number of eighth graders qualifying as regular smokers have said that they had started earlier. About six percent report that they had begun prior to the sixth grade. In general, it has been estimated that between 80 and 90 percent of regular smokers began to smoke by the age of eighteen.36

Attitudes toward Smoking among Young People Adolescent attitudes toward cigarette smoking have changed dramatically in the early years of the twenty- first century. In general, young people in middle school and high school have become less accepting of ciga- rette smoking. About 88 percent of eighth graders, for example, reported in 2011 their disapproval of someone smoking a pack of cigarettes per day, and 63 percent reported that people engaging in such behavior would present “great risk” of harming themselves physically or otherwise.

Interestingly, adolescent attitudes toward the social aspects of smoking have become more negative as well. Currently, more than half of tenth and twelfth graders agree with the statement “I strongly dislike

Quick Concept Check 10.1

Understanding the Effects of Tobacco Smoking Check your understanding of the effects of tobacco smoking by associating each of the following physical effects with (a) carbon monoxide, (b) tar, or (c) nicotine. It is possible to have a combination of two factors as the correct answer.

1. a decrease in oxygen in the body

2. physical dependence

3. cellular changes leading to cancer

4. cardiovascular disease

5. chronic bronchitis

Answers: 1. a 2. c 3. b 4. a and c 5. b

Cigarette smoking among minors is a continuing social and public health problem.

Chapter 10 Nicotine and Tobacco Use ■ 263

being near people who are smoking.” About 80 per- cent of them prefer to date nonsmokers. About six out of ten view smoking as a behavior that reflects poor judgment on the part of those who smoke, and at least seven out of ten consider smoking to be a “dirty habit.” The continuing disinclination toward dating smokers over recent years has been observed equally among males and females.37 As Lloyd D. of the University of Michigan has observed,

It now appears that taking up smoking makes a youngster less attractive to the great majority of the opposite sex, just the opposite of what ciga- rette advertising has been promising all these years. I  think this is something that teens need to know, because it may be the most compelling argument for why they should abstain from smok- ing or, for that matter, quit if they have already started.38

Since 1997, all fifty U.S. states have been required to establish eighteen as the minimum age at which tobacco products can be purchased. Vendors have been required to verify the age of purchasers up to the age of twenty-seven as a means of reducing the access of young people to tobacco. In some U.S. states, efforts are under way to raise the minimum age for tobacco purchases to nineteen or twenty-one, and other states have this higher minimum age already in effect. Any upward change from the national standard reduces the incidence of high school seniors buying cigarettes for their younger friends.

With regard to standards set in federal regulations on underage smoking, compliance rates on the part of tobacco retail vendors nationwide reached 91 percent in 2011, substantially higher than the 60 percent rate reported in 1996. Nonetheless, about 52 percent of eighth graders said in 2011 that cigarettes were fairly easy or very easy to get. This percentage is significantly lower than percentages reported in the 1990s, but it still reflects relatively easy access.39

Smokeless Tobacco Smokeless tobacco is ingested, as the name implies, by absorption through the membranes of the mouth rather than by inhalation of smoke into the lungs (Table 10.1). The two most common forms are the traditional loose- leaf chewing tobacco (brand names include Red Man and Beech Nut) and moist, more finely shred- ded tobacco called moist snuff or simply snuff (brand

names include Copenhagen and Skoal). Snuff, by the way, is no longer sniffed into the nose, as in the eigh- teenth century, but rather placed inside the cheek or alongside the gum under the lower lip. Some varieties of snuff are available in a small absorbent-paper sack (like a tea bag) so that the tobacco particles do not get stuck in the teeth. The practice is called “dipping.”

According to the 2011 University of Michigan survey, about 4 percent of eighth graders, 7 percent of tenth graders, and 8 percent of high school seniors had used smokeless tobacco within the previous thirty days. Although more than 80 percent of eighth grad- ers disapprove of others using smokeless tobacco, only about 40 percent perceive great risk in this form of tobacco use.40

Currently, the form of smokeless tobacco showing the most consistent gains in recent sales is moist snuff;

TAbLE 10.1

Forms of smokeless tobacco

TYPE DESCriPTiON

Chewing tobacco

Loose-leaf Made of cigar-leaf tobacco, sold in small packages, heavily flavored or plain

Fine-cut Similar to loose-leaf but more finely cut so that it resembles snuff

Plug Leaf tobacco pressed into flat cakes and sweetened with molasses, licorice, maple sugar, or honey

Twist Made of stemmed leaves twisted into small rolls and then folded

(Chewing tobacco is not really chewed but rather is held in the mouth between the cheek and lower jaw.)

Snuff

Dry, moist, sweetened, flavored, salted, scented

(A pinch of snuff, called a quid, is typically tucked between the gum and the lower lip. Moist varieties are currently the most popular.)

Source: Adapted from Popescu, C. (1992). The health hazards of smokeless tobacco. In Kristine Napier (Ed.), Issues in tobacco. New York: American Council on Science and Health, pp. 11–12.

moist snuff: Damp, finely shredded tobacco, placed inside the cheek or alongside the gum under the lower lip.

264 ■ Part Three Legal Drugs in Our Society

some brands are sold in cherry or wintergreen flavors. As with cigarette tobacco, variations in the alkalinity of different brands of moist snuff allow for different per- centages of the nicotine in the tobacco to be absorbed through the membranes of the mouth. Thus, snuff users typically start with brands that release relatively low levels of nicotine and then “graduate” to more potent brands. The most potent brand on the current market, Copenhagen, is also the best-selling snuff in the United States.41

Despite continuing warnings that smokeless tobacco presents great risk to one’s health, its popu- larity persists. As we have noted, although smokeless tobacco presents no immediate danger to the lungs, there are substantial adverse effects on other organs of the body. At the very least, regular use of smoke- less tobacco increases the risk of gum disease, dam- age to tooth enamel, and eventually the loss of teeth. More seriously, the direct contact of the tobacco with membranes of the mouth allows carcinogenic nitrosamines to cause tissue changes that can lead to oral cancer. Delay in the treatment of oral can- cer increases the likelihood of the cancer spreading to the jaw, pharynx, and neck. When swallowed, saliva containing nitrosamines can produce stomach and urinary tract cancer. Moreover, all the negative consequences of ingesting nicotine during tobacco smoking are also present in the use of smokeless tobacco.

In recent years, a moist snuff product called snus, the name derived from the Swedish word for snuff, has gained in popularity. In 2009, Altria, the lead- ing tobacco company in the United States, began an aggressive marketing campaign for “Marlboro snus”, a spit-less, “mess-free” smokeless tobacco product to be slid under the upper lip (with the slogan “When smoking isn’t your option, reach for Marlboro snus”). A Camel-snus product was introduced as well. Since 2010, FDA regulations have stipulated warning labels on all such products as they have appeared on other forms of smokeless tobacco.42

Cigars For a brief time in the 1990s, there was a resurgence in the popularity of cigars, spurred on by images of media stars, both male and female, who had taken up cigar smoking. The cigar suddenly was fashionable. By the end of the decade, however, the cigar-smoking craze had “gone up in smoke.” This was partly because of changing market conditions for imported cigars, but

a major contributing factor was increasing recogni- tion that cigars could not be regarded as a safe alterna- tive to cigarettes.43 Cigar smoke is more alkaline than cigarette smoke, so the nicotine content in cigars can be absorbed directly through tissues lining the mouth rather than requiring inhalation into the lungs. In addition, due to the tar content, the risk of lung cancer is five times higher for those who smoke cigars than for nonsmokers, eight times higher for those smoking three or more cigars per day, and eleven times higher for those inhaling the smoke of cigars. Regular cigar smokers have a doubled risk, relative to nonsmok- ers, for cancers of the mouth, throat, and esophagus; they also incur a 45 percent higher risk of COPD and a 27 percent higher risk of coronary heart disease (Portrait). Major cigar manufacturers have now agreed to place warning labels on their products, alerting con- sumers to the risk of mouth and throat cancer, lung cancer, and heart disease and to the hazards to fertility and unborn children.

While cigars are eligible for FDA regulation under the Tobacco Control Act of 2009, no steps have yet been taken. In 2012, congressional resolutions were passed exempting “premium cigars” from future regula- tion, on the argument that they are unlikely to appeal or be affordable to minors.44

Tobacco Use around the World Since the seventeenth century, the practice of tobacco smoking has spread throughout the world, but until the 1980s the behavior itself outside the United States had been largely independent of American tobacco corporations. Today, the picture has changed dramatically. Between 1985 and 1994 alone, U.S. cigarette exports to Japan increased 700 percent and to South Korea increased 1,200 per- cent. In the late 1990s, American-made cigarettes moved into significant markets in Eastern Europe and Russia, where smoking prevalence rates are substantially higher than those in the United States (Figure 10.3). Presently, U.S. tobacco exports total more than $6 billion each year.

Unfortunately, the prevalence rate of smoking in many foreign countries far exceeds that of the United States, coupled with substantially less public concern for the consequences of smoking on health. In the Russian Federation, Kenya, South Korea, and China, for example, more than 60 percent of all adult men smoke cigarettes. In Japan, as in many nations of the world, no-smoking sections in restaurants and

Chapter 10 Nicotine and Tobacco Use ■ 265

offices are uncommon; approximately half a million outdoor vending machines allow minors to pur- chase cigarettes easily; and only recently have there been governmental efforts to reduce smoking in general.45

Clearly, tobacco use on a global scale presents one of the most significant public health challenges we face in the twenty-first century. According to the World Health Organization (WHO), an estimated 5.4  million people worldwide die each year from tobacco-related diseases, and this figure is projected to increase to more than 810 million by 2030. In the twentieth century, tobacco smoking contributed to the deaths of 100 million people worldwide. During the twenty-first century, the death toll could rise as high as a billion people.

Making matters worse, global approaches to reduc- ing the deadly effects of tobacco use are discouragingly weak or absent. Approximately 40 percent of coun- tries in the world still allow smoking in hospitals and schools; only 5 percent of the world’s population lives in a country that imposes a comprehensive national ban on tobacco advertising. Only 5 percent of the world’s population lives in a country in which full services to treat tobacco dependence are widely available.46

In recognition of the enormous health crisis that exists at present and the potential calamity that looms in the future, a Framework Convention on Tobacco Control has been signed by more than 175 members of the World Health Organization, an agency of the United Nations. Implementation of the tobacco-use reduction initiatives in the agreement is voluntary, however, and progress on a global level has been slow. One major reason is that governments around the world collect more than $200 billion each year in taxes imposed on tobacco sales. In some cases, governments are dependent on these tax revenues to sustain their economies. In other cases, govern- ments receive direct profits from state-owned tobacco corporations.47

Quitting Smoking: The Good News and the Bad

There is no question that tobacco use of any kind is harmful to your health, as well as your wallet, and it is indeed hard to quit once you have started. But

P O r T r A i T Sigmund Freud—Nicotine Dependence, Cigars, and Cancer

Probably the best-known photograph of Sigmund Freud, founder of psychoanalysis and one- time proponent of cocaine use (see Chapter 4), shows him with a cigar in hand. Given that Freud typically smoked twenty cigars each day, it is not surprising that he did not set it aside merely to have his picture taken. But there is a story behind this photograph, a lesson about the power of smoking over the will to stop and the tragic health consequences when one’s will succumbs.

In 1923, at the age of sixty-seven, Freud noted sores on his palate and jaw that failed to heal, a sign of oral cancer. Surgery was indicated and for- tunately proved successful in remov- ing the cancerous tissue. This would be only the first of thirty-three surgical

operations on the jaw and oral cavity that Freud was to endure

for the remaining sixteen years of his life. As the leukoplakia and finally genuine carcinomas returned to his mouth, he was repeatedly warned by specialists that his practice of smoking cigars was the root of his problems and that he must stop. Despite these warn- ings, Freud kept on smoking.

Freud tried very hard to stop; indeed, sometimes he would not smoke for a few weeks at a time. In addition to his problems with cancer, he suf- fered from chest pains called “tobacco angina.” In 1936, the angina became acutely painful. His biographer, Ernest Jones, noted that it was obvious to him and to others that the pain was exacer- bated by nicotine and relieved as soon as he stopped smoking.

By this time, Freud’s jaw had been entirely removed and an artificial jaw substituted in its place. He was now almost constantly in pain, often could not speak, and sometimes could not eat or swallow. Despite the agony, Freud still smoked a steady stream of cigars until he finally died at the age of eighty-three.

Here was a man whom many consider to be one of the intellectual giants of the twentieth century. Yet the giant was a slave to his cigars.

Source: Brecher, R.; Brecher, E.; Herzog, A.; Goodman, W.; Walker, G.; and the Editors of Consumer Reports (1963). The Consumer Union’s report on smoking and the public interest. Mount Vernon, NY: Consumer Union, pp. 91–95.

266 ■ Part Three Legal Drugs in Our Society

there’s some good news with respect to the conse- quences of quitting.

The Good News: Undoing the Damage Given the grim story of all the documented health risks associated with tobacco, it is at least reassuring to know that if a smoker does succeed in quitting, some of the damage can be undone. Here are the benefits:

■ Within eight hours—Carbon monoxide levels in the blood drop to normal.

■ Within twenty-four hours—Chances of a heart attack decrease.

■ Within two weeks to three months—Circulation improves. Lung function increases by up to 30 percent.

■ Within one to nine months—Coughing, sinus con- gestion, fatigue, and shortness of breath decrease. Cilia regain normal function in the lungs and become increasingly able to handle mucus, clean the lungs, and reduce infection.

■ Within one year—Excess risk of coronary heart dis- ease is half that of a smoker.

■ Within five to ten years—Risk of stroke is reduced to that of a nonsmoker.

■ Within ten years—Lung cancer death rate is about half that of a continuing smoker.

■ Within fifteen years—Risk of coronary heart disease is equal to that of a nonsmoker.48

The Bad News: How Hard It Is to Quit The advantages of quitting are real and most people are aware of them, but the fact remains that, in the words of the surgeon general’s report in 1988, “The pharma- cologic and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine.”49 It may be easy to quit smoking for a short while, but it is very difficult to avoid a relapse, as any former or present smoker will tell you see Health Line on page 268.

About one-third of all smokers in the United States try to quit each year, the vast majority of them without any treatment, but only about 3 to 5 percent succeed with their initial attempt. Nonetheless, about half of all smokers do eventually manage to achieve

United States

France

Hungary

Greece

Argentina

Ukraine

Lithuania

Mexico

Japan

Russian Federation

South Korea

Kenya

China

Men

Women

Israel

India

Norway

United Kingdom

Canada

Sweden

Australia

67% 4%

5%

67% 32%

65%

63% 10%

53% 13%

51% 18%

51% 16%

51% 19%

47% 34%

47% 29%

44% 27%

39% 30%

26% 22%

33% 24%

29% 3%

31% 32%

27% 26%

27% 23%

19% 19%

24% 18%

F i g u r E 1 0 . 3

Smoking rates for men and women over fifteen years old in twenty countries, including the United States.

Note: As a consequence of differences in criteria and age range, percentages for the United States differ slightly from data in the National Survey on Drug Use and Health.

From The Tobacco Atlas - www.int/tobacco/en/atlas ISBN 0-92-4156-209-9. Reprinted by permission of WHO.

Chapter 10 Nicotine and Tobacco Use ■ 267

long-term abstinence from the nicotine in tobacco products, but only after an average of eight attempts at quitting. The fact that a higher level of smoking is consistently related to a lower level of education and family income makes it vital that smoking-cessation programs be available to those who ordinarily would not be able to afford them.50

The options available to smokers who want to quit are numerous. In addition to behaviorally ori- ented social support groups (Smokers Anonymous, SmokeEnders, Smoke-Stoppers), counseling either in person or through telephone “quit-lines,” hyp- nosis, acupuncture, and specific prescription drugs can help reduce the withdrawal symptoms and feel- ings of nicotine craving. One example is a sustained- release form of the antidepressant drug bupropion. Originally marketed as a treatment for depression under the name Wellbutrin, it was approved by the FDA in 1997 for use as an aid in smoking cessation and renamed Zyban when marketed for this purpose. It is recommended that Zyban be taken daily for a week prior to the last cigarette to allow drug levels to build up in the bloodstream and buffer the loss of nicotine when smoking stops. About 44 percent

of individuals taking Zyban have refrained from smoking after seven weeks, and 23 percent remain smoke-free after one year—roughly twice the per- centage among those who receive a placebo. Since 1999, the costs of all prescription medications and quit- smoking programs have been tax-deductible as medical expenses.51

In 2006, a twice-daily tablet called Chantix became available in the United States as a nicotine-free stop- smoking medication. Clinical trials of Chantix have shown that users have a rate of abstinence from tobacco of 22 percent, compared to 16 percent among those taking Zyban. Forty-eight percent of long-time, one- pack-per-day smokers quit after a twelve-week treat- ment with Chantix, compared to 33 percent among Zyban patients.52

However, despite FDA approval for both Chantix and Zyban, health risks have been identified with their use, which has resulted in the products currently carry- ing a FDA warning label that there is “a risk of serious mental health events including changes in behavior, depressed mood, hostility, and suicidal thoughts.” At the request of the FDA, the Pfizer company has begun additional clinical trials (see Chapter 14) to study the

An antismoking billboard in California, alluding to the Marlboro cowboy of past cigarette ad campaigns.

268 ■ Part Three Legal Drugs in Our Society

Health Line How to Succeed in Quitting Smoking—By Really Trying

Everyone knows how hard it is to quit smoking and how powerfully addictive nicotine can be. But everyone also knows that the long-term adverse consequences of continuing are just too severe to ignore. Here are some guidelines that can help along the way to a smoke- free life:

• Understand why you want to quit smoking in the most concrete manner you can imagine. Success comes from having a very good reason to quit, not just a nebulous notion that “it’s not good for me.”

• Don’t try it cold turkey. Nicotine is just too much a factor in your brain to let it go all at once. Do it gradually, but have a plan. Mark down dates (benchmarks) when you will be smoking less and less until you reach your goal. Understand that the first few days without a cigarette will be the most difficult.

• Try nicotine replacements to control your cravings, but don’t smoke when taking these replacements. Otherwise, you will be doubling up on your nicotine and that is the last thing you want to do.

• Don’t do it alone. Seek and accept encouragement from your non-smoking family and friends. They need to be the cheerleaders in your life as you go through this difficult time.

• Try to reduce the stress in your life. Meditate or sim- ply listen to soothing music when you feel the urge to smoke.

• Avoid the behavioral triggers that you had for smok- ing. This may include alcohol and coffee. Remember how Pavlovian conditioning works (Chapter 2) in connecting environmental cues with drug-taking behavior.

• Sweep away (maybe literally) all signs of cigarette smoking in your house. You don’t need reminders.

• Increase your level of physical exercise. Besides giv- ing yourself an alternative activity in your life, you will be surprised to see the improved breathing ability and stamina you will have as you rid yourself of inhaled smoke.

• Reward yourself for success. Do something nice for yourself as you reach your quit-smoking goals.

• Finally, if you relapse, understand that failures will occur and that this is an uphill battle. As the saying goes: If you don’t succeed, try, try again.

Some helpful online resources for those who want to quit smoking:

The American Cancer Society web site: http:// www.cancer.org/healthy/stayawayfromtobacco/ guidetoquittingsmoking/indexorg

WebMd Health, LLC, web site: www.webmd.com/ smoking-cessation/quit-smoking

The American Lung Association web site: www.lung.org/stop-smoking

link between its product Chantix and psychological side effects. The results are due in 2017. In the mean- time, some public health experts have suggested that smokers should be discouraged from using these drugs as their first attempt to stop smoking.53

Nicotine Gums, Patches, Sprays, and Inhalers The long-term goal in quitting smoking is to withdraw from dependence-producing nicotine altogether and to be totally free of any hazard associated with tobacco. In the meantime, however, it is possible to employ an alternative route of ingestion for nicotine that avoids inhaling carbon monoxide and tar into the lungs. Chewing gum containing nicotine (brand name:

Nicorette), available since the early 1970s as a pre- scription drug, is now marketed on a nonprescription basis. Transdermal nicotine patches are marketed on a nonprescription basis as well. Prescription nicotine- substitute options include a nasal spray (brand name: Nicotrol NS) and an oral inhalation system (brand name: Nicotrol Inhaler) in which nicotine is inhaled from a cartridge through a plastic mouthpiece, and loz- enges (brand name: Commit).54

The Role of Physicians in Smoking Cessation Owing to the fact that tobacco use is the leading cause of preventable death in the United States, it is clear that physicians must play a critical role in addressing the

Chapter 10 Nicotine and Tobacco Use ■ 269

issue of tobacco use in their patients as part of an inter- vention to help them quit smoking. Suggestions for a greater role of the physician in this regard have been dubbed the “Five A’s”:

■ Ask about tobacco use. Identify and document tobacco-use status for every patient at every visit.

■ Advise to quit. In a clear, strong, and personalized manner, urge every tobacco user to quit.

■ Assess willingness to make a cessation attempt. Is the tobacco user willing to make a cessation attempt at this time?

■ Assist in cessation attempt. For the patient willing to make a cessation attempt, use counseling and phar- macotherapy to help him or her quit.

■ Arrange follow-up. Schedule follow-up cont act, preferably within the first week after the cessation date.55

A recent study suggests that when physicians tell smokers their “lung age,” as determined by the age of an average healthy nonsmoker with a comparable level of breathing strength, smokers evidently get the message. They are twice as likely to quit, compared to smokers who are not informed of this fact. Unfortunately, however, the campaign encouraging physicians or other health professionals to communicate any sort of quit-smoking information to patients has a long way to go. It has been estimated that as many as 42,000 additional lives in the United States would be saved each year if 90 percent of smokers were advised by a health professional to quit and were offered medication or other assistance to do so. Presently, only 28 percent of smokers receive such services. Meanwhile, a disturbingly high percentage of physicians worldwide continue to be smokers them- selves (Figure 10.4).56

A Final Word The best strategy to stop smoking, of course, is never to start in the first place, which brings us back to the teen- age years, when virtually all adult smokers pick up the habit. The challenge as we progress through the twenty- first century will be to maintain the communication of effective messages that prevent the initiation of cigarette smoking as well as other forms of tobacco use by young people (see Chapter 16).57

Morocco

Lao People’s Democratic Republic

Indonesia

India

Iceland

Denmark

Colombia

China

Chile

Bosnia and Herzegovina

Bangladesh

Australia

Men

Women

Republic of Korea

Russian Federation

Saudi Arabia

Spain

Sweden

Syrian Arab Republic

United Kingdom

4% 2%

50%

28% 0%

55%

40% 24%

61% 12%

21% 22%

29% 20%

4% 2%

3% 0%

8% 1%

18% 0%

14% 1%

43% 1%

41% 13%

38% 16%

37% 32%

6% 6%

30% 5%

8% 6%

F i g u r e 1 0 . 4

Percentages of physicians who smoke, worldwide

From The Tobacco Atlas - www.int/tobacco/en/atlas ISBN 92-4156-209-9. Reprinted by permission of WHO.

270 ■ Part Three Legal Drugs in Our Society

Summary

Tobacco use through History ● Tobacco use originated among the original inhabit-

ants of North and South America, and its introduc- tion to Europe and the rest of the world dates from the first voyage of Columbus. Europeans used tobacco initially in the form of pipe smoking and later in the form of snuff.

● In the nineteenth-century United States, the most popular form was tobacco chewing and later cigar smoking. It was not until the late nineteenth century and early twentieth century that cigarette smoking became popular.

Health Concerns and Smoking behavior ● The 1964 surgeon general’s report, the first official

statement on the connection between smoking and adverse health consequences, produced a general reversal in the previously climbing per capita con- sumption of cigarettes.

● Since 1964, the surgeon general’s reports have solidi- fied the position that nicotine is a clearly addicting component of tobacco and that tobacco use, whether in smoked or smokeless form, causes significant health risks.

● Since 1964, there has been increased use of filtered, low-tar, and low-nicotine cigarettes.

Tobacco Today: An industry on the Defensive ● Since the early 1990s, most U.S. states, cities, and

communities have enacted laws mandating smoke-free environments in all public and private workplaces. It is now typical for restaurants, hotels, and other commer- cial spaces to be at least partially smoke-free.

● Additional pressure on the tobacco industry has come from proposals to increase the federal excise tax on tobacco products.

● Increased public pressure since the mid-1990s has resulted in a greatly limited marketing approach for tobacco products, particularly with respect to sales to young people.

● In 1998, the major American tobacco corporations entered into a $246 billion settlement agreement with all fifty U.S. states to resolve claims that the states should be compensated for the costs of treating people with smoking-related illnesses.

● In 2009, the Tobacco Control Act was signed into law, authorizing the FDA to regulate tobacco products sold in the United States.

What’s in Tobacco? ● The principal ingredients consumed during the

smoking of tobacco are nicotine, tar, and carbon monoxide.

● The smoker inhales smoke in the form of main- stream smoke (through the cigarette itself) and side- stream smoke (released from the cigarette tip into the air).

The Dependence Potential of Nicotine ● Nicotine ingestion produces both tolerance effects

and physical withdrawal symptoms. A prominent feature of nicotine withdrawal is the strong craving to return to tobacco use.

● Smokers typically adjust their smoking behavior to obtain a stable dose of nicotine.

Health Consequences of Tobacco use ● Tobacco smoking produces an increased risk of car-

diovascular diseases such as coronary heart disease and stroke, lung cancer and other forms of cancer, and respiratory diseases such as chronic bronchitis and emphysema.

● In addition to the hazards to the smoker through the inhalation of mainstream smoke, there are hazards to the developing fetus when the mother is smoking and hazards to nonsmokers who inhale environmental tobacco smoke.

Patterns of Smoking behavior and use of Smokeless Tobacco ● In 2011, the past-month prevalence rate for cigarette

smoking in the United States among people aged twelve years or older was approximately 22 percent.

● The peak years for starting to smoke are in the sixth and seventh grades of school.

● A steady increase in the prevalence of smoking among secondary school students during the 1990s has been reversed. As these young people get older, the preva- lence rates for cigarette smoking among college stu- dents and young adults are likely to decline.

● A global trend of unabated smoking rates in Asia, Eastern Europe, Russia, and elsewhere threatens the future health of huge populations of people worldwide.

Quitting Smoking: The good News and the bad ● Research has clearly shown that when people

quit smoking, many health risks diminish rapidly.

Chapter 10 Nicotine and Tobacco Use ■ 271

Unfortunately, nicotine dependence is very strong, and it is difficult to quit smoking. Nonetheless, a wide range of smoking cessation treatments are available, and about 50 percent of smokers eventually succeed in quitting on a permanent basis.

● Present-day approaches to smoking cessation include behavioral treatment programs, hypnosis, acupunc- ture, and prescription drugs to reduce withdrawal symptoms and craving, as well as a variety of nicotine substitutes.

Key Terms

arteriosclerosis, p. 258 atherosclerosis, p. 258 carbon monoxide, p. 255 carcinomas, p. 259 chronic bronchitis, p. 258 chronic obstructive

pulmonary disease (COPD), p. 258

cigarettes, p. 251 cigars, p. 250 cilia, p. 255 ciliary escalator,

p. 255 coronary heart disease

(CHD), p. 257 emphysema, p. 258

environmental tobacco smoke (ETS), p. 253

erythroplakia, p. 259 gaseous phase, p. 255 ischemic stroke, p. 258 leukoplakia, p. 259 mainstream smoke, p. 255 moist snuff, p. 263

nicotine, p. 256 nitrosamines, p. 260 particulate phase, p. 255 sidestream smoke, p. 253 snuff, p. 250 snuffing, p. 250 tar, p. 255 titration hypothesis, p. 256

Endnotes

1. Brooks, J. E. (1952). The mighty leaf: Tobacco through the centuries. Boston: Little, Brown, pp. 11–14. Fairholt, F. W. (1859). Tobacco: Its history and associations. London: Chapman and Hill, p. 13.

2. Brooks, The mighty leaf, pp. 74–80. White, J. M. (1991). Drug dependence. Englewood Cliffs, NJ: Prentice-Hall, pp. 32–33.

3. Austin, G. A. (1978). Perspectives on the history of psycho- active substance use. Rockville, MD: National Institute on Drug Abuse, pp. 1–12.

4. Brooks, The mighty leaf, p. 181. Lehman Brothers (1955). About tobacco. New York: Lehman Brothers, pp. 18–20.

5. Kluger, R. (1996). Ashes to ashes: America’s hundred-year cigarette war, the public health, and the “unabashed” tri- umph of Philip Morris. New York: Knopf, p. 14. Tate, C. (1989). In the 1800s, antismoking was a burning issue. Smithsonian, 20(4), 111.

6. Quotation originally in Bain, John, and Werner, C. (1905). Cigarettes in fact and fancy. Boston: H. M. Caldwell. Cited in Brooks, The mighty leaf, p. 259.

7. Kluger, Ashes to ashes, pp. 16–20. Lehman Brothers, About tobacco, pp. 24–27. Slade, J. (1992). The tobacco epidemic: Lessons from history. Journal of Psychoactive Drugs, 24, 99–109.

8. Lehman Brothers, About tobacco, p. 30. 9. Ibid., p. 31. 10. Connolly, G. N.; Alpert, H. R.; Wayne, G. F.; and Koh, H.

(2007, January). Trends in smoke nicotine yield and relationship to design characteristics among popular U.S. cigarette brands 1997–2005. A report of the Tobacco Research Program, Harvard School of Public Health, Boston. Federal Trade Commission Report to Congress (1992). Pursuant to the Federal Cigarette Labeling and

Advertising Act, p. 31. Centers for Disease Control and Prevention (Updated 2010, September 17). Consump- tion data: Total and per capita adult yearly consumption of manufactured cigarettes and percentage changes in per capita consumption—United States, 1900–2006. Atlanta GA: Centers for Disease Control and Prevention, Bethesda, MD: National Cancer Institute. Wilson, D. (2010, February 19). Coded to obey law, lights become Marlboro Gold. New York Times, pp. B1, B5.

11. The official web site for Philip Morris, USA, www. philipmorrisusa.com.

12. Campaign for Tobacco Free Kids, American Heart Asso- ciation, American Lung Association, and American Can- cer Society Cancer Action Network (2011, November 30). A broken promise to our children. The 1998 State Tobacco Settlement thirteen years later. Washington, DC: Campaign for Tobacco Free Kids.

13. Office of the Press Secretary, The White House (2009, June 22). Fact sheet: The Family Smoking Prevention and Tobacco Control Act of 2009. Washington, DC: Office of the President. Wilson, D. (2011, January 6). Firms told to divulge all changes to tobacco. New York Times, p. B3.

14. U.S. Department of Agriculture (2006, September 26). Tobacco outlook. Electronic Outlook Report from the Economic Research Service, Center for Tobacco Grower Research (2011, November). U.S. tobacco situation and outlook. Knoxville, TN: Center for Tobacco Grower Research.

15. Centers for Disease Control and Prevention (2008). Smoking and tobacco use: Frequently asked questions. Atlanta, GA: Centers for Disease Control and Preven- tion. Payne; Wayne A; Hahn D. B.; and Lucas, E. B. (2009). Understanding your health (10th ed.) New York: McGraw-Hill, p. 270.

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16. Schlaadt, R. G. (1992). Tobacco and health. Guilford, CT: Dushkin Publishing, p. 41.

17. Gahagan, D. D. (1987). Switch down and quit: What the cigarette companies don’t want you to know about smok- ing. Berkeley, CA: Ten Speed Press, p. 44. Payne and Hahn, Understanding your health, pp. 273–275.

18. Jacobs, M. R., and Fehr, K. O’B. (1987). Drugs and drug abuse: A reference text (2nd ed.). Toronto: Addiction Research Foundation, pp. 417–425. Julien, R. M. (2005). A primer of drug action (10th ed.). New York: Worth, pp. 233–234

19. Meier, B. (1998, February 23). Cigarette maker manipu- lated nicotine, its records suggest. New York Times, pp. A1, A15. Pankow, J. F.; Mader, B. T.; Isabelle, L. M.; Luo, W. T.; et al. (1997). Conversion of nicotine and tobacco smoke to its volatile and available free-base form through the action of gaseous ammonia. Environmental Science & Technology, 31, 2428–2433.

20. Julien, A primer of drug action, pp. 234–238. Phillips, S., and Fox, P. (1998). An investigation into the effects of nicotine gum on short-term memory. Psychopharmacol- ogy, 140, 429–433. Schuckit, M. A. (2006). Drug and alcohol abuse: A clinical guide to diagnosis and treatment (6th ed.). New York: Springer, p. 289.

21. Brecher, E. M., and the editors of Consumer Reports (1972). Licit and illicit drugs. Boston, Little, Brown, pp. 220–228. DiFranza, J. R. (2008, May). Hooked from the first cigarette. Scientific American, pp. 82–87.

22. Pontieri, F. E.; Tanda, G.; Orzi, F.; and DiChiara, G. (1996). Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Science, 382, 255–257. Risso, F.; Parodi, M.; Grilli, M.; Molfino, F.; et al. (2004). Chronic nicotine causes functional upregu- lation of ionotropic glutamate receptors mediating hip- pocampal noradrenaline and stratal dopamine release. Neurochemistry International, 44, 293–301.

23. Herning, R. I.; Jones, R. T.; and Fischman, P. (1985). The titration hypothesis revisited: Nicotine gum reduces smoking intensity. In J. Grabowski and S. M. Hall (Eds.), Pharmacological adjuncts in smoking cessation (NIDA Research Monograph 53). Rockville, MD: National Institute on Drug Abuse, pp. 27–41. Scherer, G. (1999). Smoking behavior and compensation: A review of the literature. Psychopharmacology, 145, 1–20.

24. Julien, A primer of drug action, pp. 232–247. 25. Koslowski, L. T.; Wilkinson, A.; Skinner, W.; Kent, C.;

Franklin, T.; and Pope, M. (1989). Comparing tobacco cigarette dependence with other drug dependencies. Journal of the American Medical Association, 261, 898–901.

26. Centers for Disease Control and Prevention (2008, November 14). Cigarette smoking–attributable morbid- ity, years of potential life lost, and productivity losses— United States, 2000–2004. Morbidity and Mortality Weekly Report, 57, 1226–1228.

27. Howard, G.; Wagenknecht, L. E.; Burke, G. L.; Diez-Roux, A.; et al. (1998). Cigarette smoking and

progression of atherosclerosis. Journal of the American Medical Association, 279, 119–124. U.S. Department of Health and Human Services (2004), The health con- sequences of smoking: A report of the Surgeon General. Atlanta, GA: Centers for Disease Control and Preven- tion, Chapter 3. U.S. Department of Health and Human Services (1983). The health consequences of smoking: Cardiovascular disease (A report of the surgeon general). Rockville, MD: U.S. Public Health Service, pp. 63–156.

28. Payne, W. A.; Hahn D. B.; and Lucas, E. B. (2009). Understanding your health (10th ed.), pp. 272–273.

29. Gold, D. R.; Wang, X.; Wypij, David; Speizer, F. E.; Ware, J. H.; et al. (1996). Effects of cigarette smoking on lung function in adolescent boys and girls. New England Journal of Medicine, 335, 931–937. U.S. Department of Health and Human Services, Public Health Service, Office of Smoking and Health (1984). The health con- sequences of smoking: Chronic obstructive lung disease (A report of the surgeon general). Rockville, MD: U.S. Public Health Service, pp. 329–360. U.S. Department of Health and Human Services (2004), The health consequences of smoking, Chapter 4.

30. American Cancer Society (2013). Cancer facts and fig- ures 2013. Tobacco and cancer. Atlanta, GA: American Cancer Society. Rotunno, M.; Hu, N.; Su, H.; Wang, C., Goldstein, A. M.; et al. (2011). A gene expression signa- ture for peripheral whole blood for Stage 1 lung adeno- carcinoma. Cancer Prevention Research, 4, 1599–1608.

31. Schuckit, Drug and alcohol abuse, pp. 296–297. 32. Geerts, C. C.; Grobbee, D. E.; van der Ent, C. K; de

Jong, B. M.; et al. (2007). Tobacco smoke exposure of pregnant mothers and blood pressure in their newborns. Hypertension, 50, 572–578. Li, Y-F.; Langholz, B.; Salam, M. T., and Gilliland, F. D. (2005). Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest, 127, 1232–1241. U.S. Health and Human Services (2004), The health consequences of smoking, Chapter 5.

33. Davis, R. M. (1998). Exposure to environmental tobacco smoke: Identifying and protecting those at risk. Journal of the American Medical Association, 280, 1947–1949. Ginzel, K. H. (1992). The ill-effects of second hand smoke. In K. Napier (Ed.), Issues in tobacco. New York: American Council on Science and Health, pp. 6–7.

34. Aligne, C. A.; Moss, M. E.; Auinger, P.; and Weitzman, M. (2003). Association of pediatric dental caries with passive smoking. Journal of the American Medical Associ- ation, 289, 1258–1264. Fielding, J. E., and Phenow, K. J. (1989). Health effects of involuntary smoking. Atlanta, GA: American Cancer Society. Kawachi, I.; Colditz, G. A.; Speizer, F. E.; Manson, J. E.; et al. (1997). A prospective study of passive smoking and coronary heart disease. Circulation, 95, 2374–2379. Nafstad, P.; Fugelseth, D.; Qvigstad, E.; Zahlsen, K.; et al. (1998). Nicotine concen- tration in the hair of nonsmoking mothers and size of off- spring. American Journal of Public Health, 88, 120–124. U.S. Department of Health and Human Services, Public

Chapter 10 Nicotine and Tobacco Use ■ 273

Health Service, Office of Smoking and Health (2006). The health consequences of involuntary exposure to tobacco smoke (A report of the surgeon general). Rockville, MD: U.S. Public Health Service.

35. Johnston, L. M.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2012). Monitoring the Future: National survey results on drug use, 1975–2011. Volume II. College students and adults ages 19–5. Ann Arbor, MI: Institute for Social Research, The University of Michigan, Table 2-3. Substance Abuse and Mental Health Administration (2012). Results from the 2011 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Administration,. Tables 2-1A, 2-1B, and 2-22B. Wechsler, H.; Rigotti, N. A.; and Gledhill-Hoyt, J. (1998). Increased levels of cigarette use among college students: A cause for national concern. Journal of the American Medical Association, 280, 1673–1678.

36. Centers for Disease Control and Prevention (2003). Tobacco use among middle and high school students— New Hampshire, 1995–2001. Morbidity and Mortality Weekly Report, 52, 7–9. Johnston, O’Malley, Bachman, and Schulenberg, Decline in teen smoking resumes, Table 1. Johnston, L. D.; O’Malley, P. M.; Bachman, J. G., and Schulenberg, J. E. (2012). Monitoring the future: National results for adolescent drug use 1975–2011. Volume 1: Sve- condary school students. Ann Arbor, MI: Institute for Social Research, The University of Michigan, Tables 2-1 and 6-1.

37. Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2011, December 14), Decline in teen smoking resumes in 2011. University of Michigan News Service, Ann Arbor, MI, Tables 2 and 3.

38. Johnston, L. D.; O’Malley, P. M.; and Bachman, J. G. (2002, December 16). Teen smoking declines sharply in 2002, more than offsetting large increases in the early 1990s. University of Michigan News and Information Ser- vice, Ann Arbor, pp. 4–5. Quotation by L.D. Johnston, p. 5.

39. Johnston, O’Malley; Bachman; and Schulenberg, Monitoring the future, 2004-2011, Volume 1, Table 9-6. Rigotti, N. A.; DiFranza, J. R.; Chang, Y.; Thelma, T.; et al. (1997). The effect of enforcing tobacco-sales laws on adolescents’ access to tobacco and smoking behavior. New England Journal of Medicine, 337, 1044–1057. Sub- stance Abuse and Mental Health Services Administra- tion (2012). FY 2011 annual Synar reports: Youth tobacco sales. Rockville, MD: Substance Abuse and Mental Health Services Administration.

40. Johnston; O’Malley; Bachman; and Schulenberg, Moni- toring the future, 2004–2001, Volume 1, Tables 2-3, 8-1, and 8-4.

41. Freedman, A. M. How a tobacco giant doctors snuff brands to boost their “kick.” (1994, October 26). Wall Street Journal, pp. A1, A14.

42. Information courtesy of the U.S. Food and Drug Admin- istration, Silver Springs, MD. Wilson, D., and Creswell, J. (2010, January 31). Where there’s no smoke, Altria hopes there’s fire. New York Times, pp. B1, B5.

43. Hamilton, K. (1997, July 21). Blowing smoke. Newsweek, pp. 54–60.

44. Ackerman, E. (1999, November 29). The cigar boom goes up in smoke. Newsweek, p. 55. Associated Press (2012, June 20). Cigar industry braces for new regula- tions. Baker, F., et al. (2000). Health risks associated with cigar smoking. Journal of the American Medical Associa- tion, 284, 735–740. Substance Abuse and Mental Health Services Administration (2001, December 21). The NHSDA report: Cigar use. Rockville, MD: Substance Abuse and Mental Health Services Administration.

45. Strom, S. (2001, June 13). Japan and tobacco revenue: Leader faces difficult choice. New York Times, pp. A1, A14. Tagliabue, J.(2005, September 8). The ash may finally be falling from the Gauloise. New York Times, p. A4. Watts, J. (1999). Smoking, sake, and suicide: Japan plans a healthier future. The Lancet, 354, p. 843. Winter, G.(2001, August 24). Enticing Third World youth. New York Times, pp. C1, C4.

46. Hampton, T. (2008, April 2). Global report highlights tobacco use, offers countermeasures for nations. Journal of the American Medical Association, 299, 1531–1552.

47. Marsh, B. (2008, February 24). A growing cloud over the planet. New York Times, p. 4. Shafey, O.; Eriksen, M.; Ross, H.; and MacKay, J.(2009). The Tobacco Atlas (3rd ed.). Atlanta, GA: American Cancer Society, pp. 22–23. World Health Organization (2008). WHO report on the global tobacco epidemic 2008: The MPOWER package. Geneva, Switzerland: World Health Organization. World Health Organization (2010). 2010 Global Progress Report on imple- mentation of the WHO framework convention on tobacco control. Geneva, Switzerland: World Health Organization.

48. American Cancer Society, Atlanta, GA. Cited in The world almanac and book of facts 2000 (1999). Mahwah, NJ: Primedia Reference, p. 733.

49. U.S. Department of Health and Human Services, Public Health Service, Office of Smoking and Health (1988). The health consequences of smoking: Nicotine addiction (A report of the surgeon general). Rockville, MD: Public Health Service, p. 9.

50. American Legacy Foundation (2003). Factsheet: Quit- ting smoking. Washington, DC: American Legacy Foundation. Ehrich, B., and Emmons, K. M. (1994). Addressing the needs of smokers in the 1990s. The Behavior Therapist, 17(6), 119–122. Freudenheim, M. (2007, October 26). Seeking savings, employers help smokers quit. New York Times, pp. A1, A18. Hughes, J. R.; Keely, J.; and Naud, S. (2004). Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction, 99, 29–38. Lichtenstein, E.; Zhu, S-H.; and Tedeschi, G. J. (2010, May–June). Smoking cessation quitlines: An underrecognized intervention success story. American Psychologist, 253–261. Munafò, M. R.; Clark, T. G.; Johnstone, E. C.; Murphy, M. F. G.; et al. (2004). The genetic basis for smoking behavior: A sys- tematic review and meta-analysis. Nicotine and Tobacco Research, 6, 583–597.

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51. Ahluwalia, J. S.; Harris, K. Jo; Catley, D.; Okuyemi, K. S.; and Mayo, M. S. (2002). Sustained-release bupro- pion for smoking cessation in African Americans: A randomized controlled trial. Journal of the American Medical Association, 288, 468–474. Benowitz, N. L. (1997). Treating tobacco addiction—Nicotine or no nicotine? New England Journal of Medicine, 337, 1230– 1231. Jain, A. (2003). Treating nicotine addiction. British Medical Journal, 327, 1394–1395. Zickler, P. (2003). Genetic variation may increase nicotine craving and smoking relapse. NIDA Notes, 18(3), 1, 6.

52. Nides, M.; Oncken, C.; Gonzales, D.; Rennard, S.; Watsky, E. J.; et al. (2006). Smoking cessation with varenicline, a selective alpha-4-beta-2 nicotinic recep- tor partial agonist. Archives of Internal Medicine, 166, 1561–1568.

53. Park, A. (2011, November 3). Trying to quit smoking? Don’t start with Chantix, say some experts. http:/heartland .time.com/2001/11/03.

54. Franzon, M.; Gustavsson, G.; and Korberly, B. H. (2002). Effectiveness of over-the-counter nicotine replacement therapy. Journal of the American Medical Association, 288, 3108–3110. Mathias, R. (2001). Nico- tine patch helps smokeless tobacco users quit, but main- taining abstinence may require additional treatment. NIDA Notes, 16(1), 8–9. Shiffman, S.; Dresler, C. M.; and Rohay, J. M. (2004). Successful treatment with

a nicotine lozenge of smokers with prior failure in phar- macological therapy. Addiction, 99, 83–92.

55. Fiore, M. C.; Hatsukami, D. K.; and Baker, T. B. (2002). Effective tobacco dependence treatment. Journal of the American Medical Association, 288, 1768–1771. Span- gler, J. G.; George, G.; Foley, K. L.; and Crandall, S. J. (2002). Tobacco intervention training: Current efforts and gaps in U.S. medical schools. Journal of the Ameri- can Medical Association, 288, 1102–1109.

56. Parkes, G.; Greenhaigh, T.; Griffin, M.; and Dent, R. (2008). Effect on smoking quit rate of telling patients their lung age: The Step2quit randomized controlled trial. British Medical Journal, 336, 598–600. Partner- ship for Prevention (2008). New study: Boosting five preventive services would save 100,000 lives each year. Washington, DC: Partnership for Prevention, National Commission on Prevention Priorities. World Health Organization (2002). The tobacco atlas. Geneva, Switzerland: World Health Organization, pp. 24–25.

57. Goldman, L. K., and Glantz, S. A. (1999). Evaluation of antismoking advertising campaigns. Journal of the Ameri- can Medical Association, 279, 772–777. Raising kids who don’t smoke (2003), created by Philip Morris USA Youth Smoking Prevention. Story, L. (2007, January 2). Kicking an addiction, with real people. New York Times, p. C7. Two questions to identify future smokers (2008, July 15). New York Times, p. F6.

275

After you have completed this chapter, you should have an understanding of

▶ The compounds included in the family of xanthines: caffeine, theobromine, and theophylline

▶ The sources of caffeine: coffee, tea, chocolate, soft drinks, and medications

▶ The effects of caffeine on the body

▶ The effects of caffeine on behavior

▶ The health consequences of caffeine consumption

▶ The medical uses of theophylline

▶ The effects of caffeine on children and adolescents

For a while, Steve couldn’t understand why he was suffering

those headaches. Every Sunday afternoon, sometimes ear-

lier in the day, he would get a pounding headache and

feel grumpy and out of sorts. Steve would notice that he felt

achy, as though he were coming down with the flu.

Then it occurred to him. On the weekends at home,

he was able to sleep late and drank decaffeinated coffee

instead of his regular brew at the office. He realized that

he was going through caffeine withdrawal. “I had better

cut down,” he said to himself, “or stick with regular on the

weekends.”

Caffeine

C h a p t e r

1 1

276 ■ Part Three Legal Drugs in Our Society

If you enjoy a cup of caffeinated coffee or caffein- ated tea, a piece of chocolate, or a can of “regular” Coke or Pepsi, you may be surprised to know that you are engaging in the most popular form of drug-taking behavior in the world. To varying degrees, all these prod- ucts contain caffeine, a psychoactive stimulant drug. It should be added, however, that you need not be overly concerned. Among the range of psychoactive stimulants that exist (the major ones were examined in Chapters 4 and 10), caffeine is considerably weaker than most, and research suggests that caffeine consumption is relatively benign. Nonetheless, as will be shown, caffeine can be a dependence-producing drug, and several precautions against its use should be heeded. This is particularly true in light of the recent popularity of highly caffein- ated energy drinks, with stimulant potential far exceed- ing that of traditional caffeinated beverages.

Caffeine belongs to a family of stimulant com- pounds called xanthines. Two other major examples of xanthines, theobromine (found in chocolate) and theophylline (found in small amounts in tea), also have stimulating effects. In general, theophylline and caffeine have approximately equal stimulatory effects; theobro- mine is only about one-tenth as strong. This chapter will focus on what we know about caffeine itself, beginning with a look at three natural sources of caffeine: coffee, tea, and chocolate.

Coffee

We do not know exactly when coffee drinking began, but we do know that the plant Coffea arabica, from which coffee beans were first harvested, originated in Ethiopia, and its cultivation spread to Yemen and Arabia at some time between the eleventh and the fif- teenth centuries. Coffee has been called “the wine of Islam,” suggesting that it was viewed as a substitute for alcoholic beverages, which are forbidden by the Koran.

A popular legend concerning the beginnings of cof- fee drinking has it that a young Yemenite or Ethiopian

goatherd named Khaldi, while tending his flock, noticed that his goats were unusually hyperactive and unable to sleep after nibbling some red berries in the field. Khaldi tried some himself and, upon feeling as exhilarated as his goats, took the berries to the local Islamic monastery. The chief holy man there prepared a beverage from these ber- ries and found the effect to be so invigorating that he was able to stay awake during a long night of prayers in the mosque. According to this legend, the fame of the “wake- ful monastery” and its remarkable potion spread through the whole kingdom and to other countries of the region.1

At first, coffee was banned on religious grounds because some Islamic clerics considered it to be as much an intoxicant as an alcoholic beverage, but these ecclesiastic disputes were eventually settled and cof- fee drinking became a fixture of daily life. In the words of one historian, “The growth of coffee and its use as a national beverage became as inseparably connected with Arabia as tea is with China.”2

Coffee in Britain and North America The practice of coffee drinking reached England in the middle of the seventeenth century, just in time to be associated with one of the most turbulent periods of political, social, economic, and religious unrest in its history. It was in establishments specializing in the sale of coffee, known as coffee houses, that intellectuals met and argued their respective points of view. Until the end of the eighteenth century, when tea began to replace coffee as the dominant British drink, coffee was the principal alternative social beverage to alco- hol. The British coffee house enjoyed the reputation

caffeine: A xanthine stimulant found in coffee, tea, chocolate, soft drinks, and several medications.

xanthines (ZAN-theens): A family of CNS stimulant drugs that includes caffeine, theophylline, and theobromine.

theobromine (THEE-oh-BROH-meen): A xanthine stimulant found in chocolate.

theophylline (thee-OFF-ill-lin): A xanthine stimulant found in small amounts in tea. It is used as an antiasthma medication.

by the numbers . . .

80 Milligrams of caffeine in an 8.3-ounce can of Red Bull, the leading “energy drink” in the U.S. market. The caffeine content in a 12-ounce serving is approximately 3 times that in a 12-ounce can of Coca-Cola Classic.

260 Milligrams of caffeine in a 12-ounce Star- bucks Tall coffee, approximately 7½ times that of a 12-ounce can of Coca-Cola Classic.

9 The number of ounces in an average cup of coffee in the United States. The “standard drink size” for coffee has traditionally been five ounces.

Sources: Energyfiend.com, 2013.

Chapter 11 Caffeine ■ 277

of being a place where men could socialize with one another and enjoy a nonintoxicating beverage in sober company. (Women rarely frequented coffee houses, although they often managed them.)

The emphasis was on keeping a clear head, which was certainly not likely after an hour or two at the local tavern. In fact, historians have credited coffee houses with helping to moderate the widespread drunkenness that was rampant as a result of the “gin epidemic” in England during the 1700s (see Chapter 8). A popular nickname for coffee houses was “penny universities,” since the conversation there was considered to be as stimulating as a university education and a lot cheaper.3

Coffee houses in colonial America served a similar purpose. One such political gathering place, the Green Dragon in Boston, was the setting for meetings of John Adams, Samuel Adams, Paul Revere, and their compa- triots as they planned their strategy against the British. After the Revolutionary War, coffee emerged as the American national drink, especially after 1830 when alcohol consumption began to decline (see Chapter 8). During the settling of the American frontier, coffee was an indispensable provision for the long trek westward. By 1860, Americans were consuming three-fourths of the world’s entire production of coffee.

Today, the United States remains the world’s top importer of coffee (Germany being a close second), with most of our imported coffee originating in Brazil, Colombia, and Vietnam. However, in terms of per capita coffee consumption, the United States barely ranks among the top twenty-five nations of the world. Most European countries exceed the U.S. in per capita consumption, with Finland being number one (about 27 pounds/12.2 kilograms in a year). Since roughly 1960, domestic coffee consumption has gradually declined as American drinking habits have shifted to an increased consumption of colas, particularly among young adults.4

Major Sources of Coffee The global coffee market is represented by two species of coffee beans. Coffea arabica, the original coffee bean as far as Westerners are concerned, is grown mostly in Brazil and Colombia, having been brought to South America by the French in the early 1700s. The other species, Coffea robusta, was originally grown primarily in formerly Dutch plantations on the Indonesian island of Java (hence the phrase “a cup of java” for a cup of cof- fee). Vietnam is currently the leading grower of robusta coffee, followed by Brazil, India, and several countries in Africa. Coffea arabica beans represent about 80 per- cent of the world’s coffee production.

Coffee blends are made up of combinations of these two types of beans, with the ratio dictated by local tastes and economic concerns. Robusta beans are considered by coffee experts to be inferior to arabica beans because of their harsher taste, but robusta beans have approxi- mately twice the caffeine content and are cheaper to buy. In recent years, “100 percent Arabica bean” coffee has become the norm for most coffee retailers in the United States.

The Caffeine Content in Coffee Caffeine is the only xanthine found in coffee (see Drugs . . . in Focus), with the caffeine content in a “standard” 5-ounce cup of coffee ranging from about 57 to 145 milligrams (mg). The precise caffeine dos- age depends on the method of brewing, the amount of coffee used, brand of coffee, and brewing time. Roughly speaking, the caffeine content in coffee can be

Expert coffee tasters in a German coffee company sample the possibilities before deciding on a particular blend.

Coffea arabica (KOFF-ee-uh air-RAB-beh-ka): A type of coffee bean native to the Middle East but now grown principally in South America. It is typically referred to simply as arabica.

Coffea robusta (KOFF-ee-uh row-BUS-tah): A type of coffee bean grown principally in Indonesia, Brazil, and Africa.

278 ■ Part Three Legal Drugs in Our Society

estimated to be about 100 mg (20 mg per fluid ounce). Comparable amounts of instant coffee have about 60 mg of caffeine (12 mg per fluid ounce).5

Bear in mind, however, that the average regular- size cup of coffee holds about 9 ounces, and a 12- to 24-ounce cup is often the preferred serving size, so you have to do the math carefully to determine the actual amount of caffeine you are ingesting in a given day.

Tea

By the standard of historical records, tea is the world’s oldest caffeine-containing beverage. The legendary Chinese emperor Shen Nung is credited with its dis- covery in 2737 b.c., along with other stimulants such as the anti-asthma medication we now know as ephedrine (see Chapter 4) and marijuana (see Chapter 7). Tea is a brew of leaves from the Camellia sinensis (tea plant), a large evergreen tree that is typically trimmed back to look more like a bush. The Latin word sinensis refers to its origin in China.6

Dutch traders brought tea from Asia to Western Europe in the early 1600s, where it met with mixed reviews. The Germans tried tea drinking for a while, but then returned to beer; the French also tried it, but

then returned to coffee and wine. The Chinese traded directly with the Russians, who became enamored with tea and made drinking it a national pastime. Giant tea urns, called samovars, kept tea available for drinking throughout the day.

Tea in Britain and North America The principal Dutch success with tea in Europe was in Britain, where it eventually became the national drink. Chinese tea, as noted in Chapter 5, was in such great demand by the British that the Chinese were forced to trade their tea in exchange for opium imported by the British into their own country. By 1842, the problems with this odd arrangement escalated into the Opium War, pitting China against Britain and later France and the United States.

By the end of the nineteenth century, however, China was no longer the principal source for British tea. Tastes had shifted away from the subtle flavor of Chinese green tea leaves and toward a stronger, blacker tea that was being grown in India and Ceylon (now Sri Lanka). It also did not hurt that a greater number of cups could be made from a pound of Indian or Ceylonese tea, making it more economical for the average consumer. Today’s teas are blends of black tea leaves, chiefly from India, Sri Lanka, and Indonesia, although there is a growing market for green tea from China and Japan.7

We do not know whether the gentlemen at the Green Dragon coffee house in Boston were drinking

Drugs . . . in Focus

Why There Are No (Live) Flies in Your Coffee Chemical compounds found naturally in plants are generally there because they confer some selective advantage, although it may take a while for scientists to figure out what that advantage may be. In the case of plants containing xanthines, the benefit lies in the area of insect control.

We now know that xanthines interfere with an insect’s ability to feed on a plant because they increase the level of octopamine, an excitatory chemical in the nervous system of invertebrates. As a result, contact with xanthine-containing

plants causes insects to become overly stimulated and die. Fortunately, octopamine plays little or no role in mam- malian nervous systems. One extra benefit in knowing how xanthines affect insects is the possibility in the future of developing xanthine-based pesticides that are effective on cockroaches but a good deal safer for human beings.

Sources: Hirashima, A.; Morimoto, M.; Kuwane, E.; and Eto, M. (2003). Octopaminergic agonists for the cock- roach neuronal octopamine receptor. Journal of Insect Science, 3, 1–9. Nathanson, J. A. (1984). Caffeine and related methylxanthines: Possible naturally occurring pesticides. Science, 226, 184–187.

Camellia sinensis (ka-MEE-yah sin-EHN-sis): The plant from which tea leaves are obtained.

Chapter 11 Caffeine ■ 279

coffee or tea during the months of growing unrest and resentment against the British prior to the beginning of the Revolutionary War, but much of the talk certainly concerned tea. In 1773, the British government had decided to allow British agents to sell cheap tea directly to the American colonies, bypassing American tea mer- chants in the process. In the eyes of the Americans, the policy was another instance of British tyranny and one more reason why the colonies should be independent.

We do know what happened next. On the night of December 16, 1773, while three British ships loaded with chests of British tea lay at anchor in Boston Harbor, fifty to sixty colonists, some of them dressed as Mohawk Indians, boarded the vessels and proceeded to break open the tea chests and dump the contents into the water. Thus the Boston Tea Party entered the pages of history. Strangely enough, the initial reaction to this event in British newspapers focused not on the political ramifications but rather on the pharmacologi- cal effect of the tea on the unfortunate fish in Boston Harbor. One London newspaper reported that the fish “had contracted a disorder not unlike the nervous complaints of the body.” Assuming this story is true, we can only conclude that all that tea had given the fish a large dose of xanthines, specifically caffeine and theophylline (see below).8

Largely as a result of continuing anti-British sen- timent during the early history of the United States, drinking tea was viewed as unpatriotic, and coffee became the preferred beverage. Today, American con- sumption of tea is only approximately one-eighth that of Ireland and Great Britain, who lead the world, as you might suspect, in per capita tea drinking. More than 80 percent of all tea consumed in the United States is in the form of iced tea, a beverage that was introduced at the Louisiana Purchase Exposition in St. Louis in the summer of 1904.

The Chemical Content in Tea Tea contains caffeine and theophylline. The caffeine content of a 5-ounce cup of medium-brewed tea is approximately 60 mg. If the tea is a strong brew, the caffeine content approaches that of regular coffee, especially if the tea is produced in Britain rather than the United States. A strong brew of Twining’s English Breakfast tea, for example, contains approximately 107 mg of caffeine in a 5-ounce cup. Of course, as with coffee, caffeine amounts in the tea consumed will be higher if the drink size is greater.9

The other xanthine found in tea, theophylline, is found in much smaller concentrations than caffeine.

As will be noted later, its bronchodilating effect is clini- cally useful for the treatment of asthma and other respi- ratory problems.

A growing medical literature points to the poten- tial health benefits in the consumption of a group of non-xanthine chemicals in tea, called polyphenols. Polyphenols are plentiful in green tea and, to a lesser degree, in black or pekoe tea. Although both types of tea are harvested from the Camellia sinensis plant, they are processed differently. Black tea leaves are fer- mented prior to drying, whereas green tea leaves are not. During the fermentation process, black tea loses most of its polyphenol content. Beneficial effects have been studied in the prevention of cardiovascu- lar disease, inflammatory disorders, neurogenerative disorders such as Parkinson’s disease and Alzheimer’s disease, as well as some forms of cancer. Whether green tea is a “miracle drink” remains, however, to be determined. Green tea may not be beneficial in all circumstances. For example, green tea contains vita- min K (a clotting factor), raising the potential for inter- fering with blood-thinning medications, and it can reduce the absorption of iron from the diet. There is also evidence that polyphenols can interfere with the action of certain anti-cancer treatment drugs.10

Chocolate

Chocolate comes from cocoa bean pods growing directly on the trunk and thick main branches of cacao trees. Cacao trees are native to Mexico and Central America, but now they are grown in tropical regions of the Caribbean, South America, Africa, and Asia. The leading exporters of cocoa beans to the United States are the Ivory Coast, Ghana, and Indonesia.11

According to popular legend, chocolate was a gift from the Aztec god Quetzalcoatl to give humans a taste of paradise. At the time of Hernando Cortés’s expedition to Mexico in 1519, chocolate (xocoatl or chocolatl as the Aztecs called it) was a prized bever- age, to be enjoyed only by the rulers and the upper classes of society. Cortés took some cocoa bean pods back to Spain in 1528 and made a preparation as he had learned it from the Aztecs, but with an important difference: the addition of sugar. Now, in a sweetened form called molinet, chocolate became an instant

cocoa bean pods (COH-coh): Parts of the cacao tree that are the raw material for cocoa and chocolate. Not to be confused with coca, the source of cocaine.

280 ■ Part Three Legal Drugs in Our Society

success—and a closely guarded secret of the Spanish emperor Charles V and his royal court. Inevitably, however, word leaked out to the other royal courts of Europe that the Spanish were enjoying an exotic new drink that came from the New World.

W h e n t h e f o u r t e e n - y e a r - o l d S p a n i s h p r i n - cess arrived in Paris to marry the fourteen-year-old Louis XIII of France in 1615, she carried with her a betrothal gift of Spanish chocolate. It was the begin- ning of the traditional connection of chocolate with romance. Later, in 1660, a similar betrothal gift at the wedding of another Spanish princess and Louis XIV of France sealed its reputation as the gift of love. It also has not hurt chocolate’s image that the eighteenth-century Italian lover Casanova credited his considerable sexual prowess to a habit of drinking chocolate each morning. Of course, the true expla- nation could have been either the stimulating effects of caffeine, or simply a powerful placebo effect (see Chapter 1).

Chocolate took hold in England not so much as a symbol of romance but simply as another good- tasting beverage that could be sold in the growing number of coffee houses in English cities. From the beginning, chocolate was sold in shops rather than hidden away behind palace walls. It was not cheap, but at least it was available to all who could afford to buy it. By 1700, the specialty chocolate house rivaled the coffee house as a place to gather and discuss cur- rent events.

How Chocolate Is Made The preparation of modern-day chocolate begins with the roasting of cocoa beans to such temperatures that the natural fat within the beans, called cocoa butter, melts. The result is a deep-colored chocolaty-smelling paste called chocolate liquor. When it later cools and hardens, the paste is called baking chocolate. As chocolate, it is as pure as you can get, but since there is no sugar content it has an “extra-bittersweet” flavor, suitable only for cakes, brownies, and other baking purposes.

To make chocolate that is eaten by itself, sev- eral additional processing steps are required, many of which were developed by the Swiss chocolatier Rodolphe Lindt in 1879. A ratio of cocoa liquor and cocoa butter is combined with milk, sugar, and vanilla to make milk chocolate. Just how much cocoa liquor is added depends on the type of chocolate. Dark (semi- sweet) chocolate is made with much less milk and less sugar than milk chocolate, with the percentage of cocoa liquor typically in the 60% to 75% range. The percentage of cocoa liquor is higher in “extra dark” versions.

Fortunately, unlike other fats, cocoa butter almost never goes rancid. In other words, chocolate keeps. It might turn white after a while, but that simply means that the cocoa butter is starting to separate from the mixture. It is all right to eat, although chocolate con- noisseurs would surely disagree. All that is needed to produce commercial chocolate is to refine the texture to achieve that degree of smoothness the world has come to know and love—not to mention a consum- able product that, despite its detrimental effect on the waistline, appears to have genuine health benefits (Health Line).12

The Chocolate Industry Today Present-day domestic sales of chocolate in the United States are dominated by the Hershey Company and Mars, Incorporated, which together hold approxi- mately 75 percent of an annual market (see Portrait). Overall, the annual per capita consumption of chocolate in the United States is approximately 11 pounds, which puts the country well below that of other chocolate-loving nations of the world. Not sur- prisingly, Switzerland ranks first in the world, con- suming about twice as much on an annual per capita basis.13

The Xanthine Content in Chocolate The amounts of xanthines are much smaller in choc- olate than in coffee or tea. A typical 1–ounce piece of milk chocolate, for example, contains about 6-8 mg of caffeine and about 40 mg of theobromine. With theo- bromine packing about one-tenth the stimulant power of caffeine, the total effect of this quantity of chocolate is roughly equivalent to that of 10–12 mg of caffeine. Of course, eating more than 1 ounce will change these figures (a typical chocolate bar is approximately 1.5 ounces), but even so, it is unlikely that chocolate will keep you up at night.14

cocoa butter: The fat content of the cocoa bean. chocolate liquor (lih-KOOR): A deep-colored paste made when roasted cocoa beans are heated so that the cocoa butter in the beans melts.

baking chocolate: A hardened paste, consisting of chocolate liquor, produced by heating roasted cocoa beans.

Chapter 11 Caffeine ■ 281

Soft Drinks

The fourth and final major source of caffeine in our diet is soft drinks. Table 11.1 shows the caffeine content of prominent soft-drink brands. Although most of the caf- feinated drinks are colas, it is possible for a noncola to be caffeinated as well. The reason is that more than 95 percent of the caffeine in caffeinated soft drinks is added by the manufacturer during production; less than 5 percent actually comes from the West African kola nut, from which cola gets its name.

In general, the United States leads the world in per capita consumption of soft-drink products, about 45 gal- lons annually (a bit less than two 8-ounce servings per day). Traditionally, almost all of the major caffeinated soft drinks (Coca-Cola and Pepsi-Cola products being the leaders), have contained caffeine levels in the range of 3–5 mg per fluid ounce. Recently, a new category of highly caffeinated soft-drinks (such as Red Bull and Monster Energy) have entered the market and are cur- rently the fastest-growing segment of the beverage indus- try (see Table 11.3, page 285). In addition, new products

of highly concentrated caffeinated beverages, so-called energy shots, have been introduced (see Drugs . . . in Focus, page 289).15

Caffeine from OTC Drugs and Other Products

Caffeine is sold purely as a stimulant in over-the-counter (OTC) drugs such as NoDoz and Vivarin tablets and as one of several ingredients in a number of other products ranging from pain relievers and cold remedies to diuretics and weight-control aids. As Table 11.2 shows, the equiva- lent caffeine level in these products ranges approximately from that of one-third cup to two cups of regular coffee.

The availability of caffeine in OTC drugs has recently been supplemented by novelty products such as caffeinated lip balm, caffeinated sunflower seeds, caffein- ated beer, and even caffeinated soap (promoted as waking you up while the coffee is brewing). Inhalable caffeine (brand name: AeroShot), equivalent to a large-size coffee and sold in lipstick-sized canisters, became available in

Health Line Chocolate, Flavanols, and Cardiovascular Health

Are we running any risk to our health by indulging in our obvious love for chocolate? It is true that chocolate is rich in saturated fatty acids, many of which are villains when it comes to raising cholesterol and clogging our coronary arteries. Yet the particular saturated fatty acid in the cocoa butter of chocolate turns out to be quite benign. The main component of cocoa butter is a fatty acid known as stearic acid, which is rapidly converted in the liver to oleic acid, a mono-unsaturate that neither raises nor lowers serum cholesterol. One study found that healthy young men on a twenty-six-day diet in which a total of 37 per- cent of calories came from fat and 81 percent of those fat calories came from cocoa butter had no increase in their serum cholesterol, and their cholesterol levels were no higher than if they had been on a comparable diet in which the fat came from olive oil (see Chapter 1).

Recent evidence suggests that chocolate may even pro- tect arteries from disease. Cocoa liquor has a concentration of compounds called flavanols that are known to function as antioxidants of the bloodstream. The greater the level of antioxidants, the lower the probability that artery-clogging cells will develop. This is consistent with recent studies indicating that dark chocolate is associated with reducing the risk of cardiovascular disease and stroke. Dark chocolate has twice the flavanols of milk chocolate. This is not to say

that chocolate should be considered a substitute for fruits and vegetables, foods that have obvious nutritional virtues. Nor should chocolate necessarily be viewed as a health food. Milk chocolate contains by definition (and by law) a minimal amount of milk-derived butterfat in addition to cocoa butter. Some chocolates also contain palm oil or coconut oil, two saturated fats that do raise cholesterol lev- els. And no one should expect to lose weight on a chocolate diet. Even so, nutritionists are concluding that there is little harm in eating two or three chocolate bars a week, which is welcome news for chocolate lovers everywhere.

Sources: Barnett, C. F., and DeMarco, T. (2011). A chocolate a day keeps the doctor away? Journal of Physiology, 589, 5921–5922. Buitrago-Lopez, A.; Sanderson, J.; Johnson, L.; Warnakule, S.; Wood, A.; et al. (2011). Chocolate consump- tion and cardiometabolic disorders: Systematic review and meta-analysis. British Medical Journal, accessed BMJ 2011; 343:d4488 doi. Grassi, D.; Lippi, C.; Necozione, S.; Desideri, G.; and Ferri, C. (2005). Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. American Journal of Clinical Nutrition, 81, 611–614. Waterhouse, A. J.; Shirley, J. R.; and Donovan, J. I. (1996). Antioxidants in chocolate. Lancet, 348, 834.

282 ■ Part Three Legal Drugs in Our Society

P O R T R A i T Milton S. Hershey and the Town Built on Chocolate

When Milton Hershey made a decision in 1893 to go into the chocolate business, he was already an experienced confectioner with a prosperous caramel company in Lancaster, Pennsylvania. At the time, caramels were the dominant candies in America, but he could see that the future was in chocolate. New German-built machinery was now available to mass-produce milk choco- late. As Hershey had observed during a trip to Switzerland a few years earlier, chocolate was already all the rage in Europe. He wanted to be in the busi- ness on the ground floor.

Hershey bought the equipment and started to experiment on a special recipe, using fresh milk from the local dairy farms instead of powdered milk. The proportions of milk and sugar, the blend of cocoa beans, and the roasting time are secrets to this day. All we know is that somehow Hershey devised a recipe that was a winner.

The new Hershey bar was an instant hit.

By 1903, the Hershey chocolate business had become so successful that it needed a new factory. Defy- ing conventional wisdom, however, Hershey did not look for a town or city for the factory but rather went into the surrounding countryside. He bought a thousand acres of prime Pennsylvania Dutch farmland, built his factory, then decided to build a town around it.

By 1930, the town of Hershey had grown to include residents beyond the six thousand factory workers. The Her- shey business was now worldwide, with its chocolate “kisses” and chocolate syrup in addition to other products. During hard economic times, Hershey went on a construction spree to main- tain employment. He built the famous Hershey Hotel, Hershey Gardens, a football stadium and sports arena, and a convention center. Because he was childless, he turned his attention to

building a Milton Hershey school for orphaned boys and girls.

Milton Hershey died in 1945 at the age of eighty-eight, but his corporate heirs continued in his spirit. Today, there is the Milton S. Hershey Medi- cal Center of the Pennsylvania State University, endowed by the Hershey Company. And of course there is Hersheypark, an enlargement of an old amusement park Hershey had built in 1905, all powered by a best- selling chocolate bar and a man with a very sweet dream.

Sources: D’Antonio, M. (2006). Hershey: Milton S. Hershey’s extraordinary life of wealth, empire, and utopian dreams. New York: Simon and Schuster. Kennedy, P. (2013, January 13). Who made that? (Hershey bar). New York Times Magazine, p. 15. Morton, M., and Morton, F. (1986). Chocolate: An illustrated history. New York: Crown Publishers, pp. 89–125

TABlE 11.1

Caffeine levels and domestic U.S. market share of leading brands of soft drinks

BRANd NAME (COMPANy)

MARKET SHARE (2011)

CAFFEiNE CONTENT

(MG/12 OZ.)

Coke (Coca-Cola) 17.0% 34

Diet Coke (Coca-Cola) 9.7% 45

Pepsi-Cola (PepsiCo) 9.2% 38

Mountain Dew (PepsiCo) 6.7% 55

Sprite (Coca-Cola) 5.7% none

Diet Pepsi (PepsiCo) 4.9% 36

Diet Mountain Dew (PepsiCo)

2.0% 55

Fanta (Coca-Cola)

Diet Dr Pepper (Dr. Pepper Snapple)

1.9%

1.8%

41

none

Note: Diet Coke became the Number Two brand for the first time in history in 2011. Sources: Energyfiend.com, 2013. Top soft drink brands, 2011. Market Share Reporter (2012). Detroit: Gale. Business Insights: Essentials Web. April 2013.

2011, not requiring FDA approval since it is marketed as a dietary supplement (Chapter 1). Nonetheless, the FDA has since issued a warning letter to the manufacturer that the product label must address issues of safety, possible use by children and adolescents, and possible use with alcohol. Concerns that AeroShot might become another club drug are similar to those that had been raised with respect to the briefly popular caffeinated alcohol drink Four Loko (see Drugs . . . in Focus, Chapter 8).16

Caffeine as a Drug

When ingested orally, caffeine is absorbed in about thirty to sixty minutes. Caffeine levels peak in the bloodstream in one hour, and reactions in the central nervous system peak in about two hours. Many coffee drinkers notice a boost of energy, or “buzz,” almost immediately, but this effect is attributable either to the sugar in the coffee or to a conditioned learning effect, not to the caffeine itself. From three to seven hours after caffeine is consumed, approximately half of it still remains in the bloodstream.

The biotransformation of caffeine and the time it takes to eliminate it vary according to a number

Chapter 11 Caffeine ■ 283

of factors. For example, women in late stages of preg- nancy and those using oral contraceptives eliminate caf- feine from their systems more slowly than either men or women in general. Infants and the elderly also show a slower elimination of caffeine. In contrast, smokers eliminate caffeine about 100 percent more quickly than nonsmokers. As a result, smokers on average experience the effect of the caffeine they consume for a relatively shorter period of time; it is possible that smokers tend to drink more caffeinated coffee than nonsmokers to com- pensate for their faster elimination of caffeine.17

Effects of Caffeine on the Body The stimulant effects of caffeine, as well as those of the other xanthines, are a result of a “double-negative effect.” Essentially, caffeine is a stimulant because it inhibits an inhibitory factor in brain functioning. In this case, caf- feine blocks the effects of an inhibitory neurotransmitter called adenosine. Normally, adenosine binds to recep- tors on the surface of cells and consequently produces sleepiness, dilation of blood vessels, and constriction of bronchial passageways. It also protects the body against seizures; slows down the body’s reaction to stress; and lowers heart rate, blood pressure, and body temperature.

By inhibiting the effects of adenosine, caffeine and other xanthines cause the opposite responses to occur, although the actual results are complex. In general, peripheral blood vessels are dilated, while cerebral blood vessels in the head are constricted. Because dilated blood vessels in the head can frequently result in headache pain, caffeine can help headache sufferers, and that is why it is found in many over-the-counter pain relievers. Heart rate is slightly elevated when caffeine is consumed, but the effect is dose-dependent and often is not observed at all.

The fact that caffeine has a bronchodilating effect makes it helpful in treating asthmatic conditions in which the bronchial passageways are abnormally con- stricted. Theophylline, however, has a stronger bron- chodilating effect than caffeine and so can be prescribed at lower doses. Caffeine is effective, but patients often report unpleasant side effects of “jitteriness” prior to improvement in their asthmatic condition.18

Effects of Caffeine on Behavior As a stimulant, caffeine excites neuronal activity in the brain. As the dose increases, the effects expand from the

TABlE 11.2

Caffeine content in common over-the-counter medications

MEdiCATiON

CAFFEiNE PER TABlET OR CAPSUlE

(in milligrams)

CAFFEiNE PER RECOMMENdEd

dOSAGE (in milligrams)

Stimulants

NoDoz 100 200

Vivarin 200 200

Pain relievers

Anacin 32 64

Excedrin 65 130

Midol 32 64

Vanquish 33 66

Cold remedies

Coryban-D 30 30

Dristan 16 32

Triaminicin 30 30

diuretics

Aqua-Ban 100 200

Note: Caffeine is also found in prescription remedies for migraines (Cafergot and Migral) and in pain relievers (Darvon Compound and Fiorinol).

Source: Updated from Gilbert, R. J. (1986). Caffeine: The most popular stimulant. New York: Chelsea House, p. 51.

Quick Concept Check 11.1

Understanding Caffeine Levels in Foods and Beverages Check your understanding of the relative amounts of caf- feine in various foods and beverages by rank ordering the following caffeine-containing foods or beverages, from 1 (most) to 6 (least). If any examples have caffeine levels close enough to be considered a tie, indicate this in your ranking.

a. 1-ounce bar of milk chocolate

b. 5-ounce cup of drip-brewed coffee

c. 5-ounce cup of tea

d. 12-ounce can of Coca-Cola

e. 5-ounce cup of instant coffee

f. 5-ounce cup of decaffeinated coffee

Answers: a. 5 b. 1 c. 2 (tie) d. 4 e. 2 (tie) f. 6

adenosine (a-dEN-oh-seen): An inhibitory neurotransmitter that is blocked, or neutralized, by caffeine and other xanthines. The action on adenosine receptors in the body is the basis for the stimulant properties of these drugs.

284 ■ Part Three Legal Drugs in Our Society

cerebral cortex downward to lower systems in the brain and finally to the spinal cord (Chapter 3). The behav- ioral consequence of this excitation is a feeling of men- tal alertness and lack of fatigue.

On the basis of these effects, you might expect that caffeine would also improve human performance, but reports in this regard are mixed. Subjects in controlled experimental settings feel stimulated and more alert, but whether their performance improves after caffeine depends on the type of task, their personal characteristics, and even the time of day when the experiment is conducted. In a recent study of possible performance-enhancing effects among competitive cyclists, it was found that caffeine administration increased their performance during timed trials overall, but the effect was greater when the cyclists were (falsely) informed that they had not ingested it.19

Nonetheless, it is possible to make some generaliza- tions about caffeine’s effect on performance. In general, caffeine increases vigilance and attentiveness in tasks at which subjects become easily bored, and it decreases the response time to simple visual or auditory signals. For more complex tasks in which subjects need to make decisions or in situations that require motor coordina- tion, however, caffeine either has little effect or can be disruptive. Most reports of improvements under caffeine involve conditions in which the subject is already either bored or fatigued. In these circumstances, caffeine helps either to maintain a level of performance that would otherwise have declined or to restore performance from a state degraded by boredom or fatigue. Caffeine, there- fore, can serve to support a moderate level of arousal and attention that is optimal for the task at hand.20

The best-known effect, however, is the impact on sleep. Caffeine lengthens the time it takes to fall asleep and reduces the quality of sleep once it comes. Generally, studies investigating caffeine effects have involved coffee drinking, and the sleep effects are seen more strongly in nondrinkers of coffee than in habitual heavy coffee drinkers.21

As a final note, it is important to understand what interacting effects caffeine may or may not have on alco- hol intoxication. First of all, caffeine does not have the ability to sober up a person recently intoxicated with alcohol. Despite the widespread notion that a cup of strong black coffee will help someone who is drunk, the evidence is simply not there. If anything, the behav- ioral consequences of alcohol intoxication can worsen. Second, the ingestion of highly caffeinated energy drinks (see Table 11.3) as mixers with alcohol at bars and clubs will not reduce alcoholic intoxication, as mea- sured by objective tests. The combination reduces peo- ple’s perception of intoxication, leading them to believe that they are more in control than they actually are. As a result, caffeinated energy drinks can make it more likely that greater amounts of alcohol will be consumed.22

Potential Health Benefits

In 2000, an intriguing connection was found between caffeine consumption and a lower risk of developing Parkinson’s disease. In a follow-up of about eight thousand Japanese American men in Honolulu, the incidence of Parkinson’s disease was about one-fifth in men who con- sumed at least 28 ounces of coffee per day, compared to those who consumed none at all. A lower risk of Parkinson’s disease was observed no matter what the source of the caf- feine and independent of intake levels of milk and sugar.

A second study in 2001 involving a larger sample of men confirmed this relationship, but it is presently uncertain whether the same relationship exists in women. In studies in which a lower risk is found in women, there is a U-shaped function for women, with either low or high consumption levels being less pro- tective than moderate ones; for men, the higher the caffeine intake, the better the protection. The gender differences in the health consequences of caffeine consumption appear to be related to hormonal fac- tors in women, specifically the interaction of caffeine and estrogen. A recent study has shown that caffeine reduces the risk of Parkinson’s disease among post- menopausal women who do not take replacement estro- gen; for those women who do take this therapy, caffeine increases the risk of the disorder. There is also evidence

Caffeine is typically most effective for warding off sleep and improving performance on tedious tasks, at home, at school, and in the workplace.

Chapter 11 Caffeine ■ 285

that caffeine intake may reduce the risk of the cognitive decline, though the effects are stronger for women than for men.23

Potential Health Risks

Studies investigating the potential adverse health conse- quences of caffeine consumption have been conducted for more than a century, and the conclusions have varied considerably. In some cases, earlier concerns have been determined to be unfounded. For example, a 1971 study indicating an association between caffeine consumption and urinary tract cancer and a 1981 study indicating an association with pancreatic cancer were both com- promised methodological design flaws. At present, the medical consensus is that caffeine consumption is not causally related to these or other types of cancer.24

Cardiovascular Effects Because it is known that caffeine stimulates cardiac mus- cle as well as skeletal muscle throughout the body, it is only natural to be concerned with the possibility that caf- feine consumption would be a risk factor for a heart attack or cardiac arrhythmia (irregular heart beat). In 1973, a great deal of publicity was generated by a study called the Boston Collaborative Drug Surveillance Program in which a large number of individuals at Boston metro- politan hospitals were surveyed as to their use of many different drugs, including caffeine, and the incidence of various disease states. The researchers reported that the consumption of more than six cups of caffeinated coffee a

day more than doubled the risk of a heart attack. Further studies, however, have failed to find any connection at all between caffeine and heart attacks.25

What do we do when the medical literature is so inconclusive and contradictory? First of all, in caffeine studies that show some cardiovascular health risk, the con- sumption levels are rather high (five to six cups or more a day). Drinking less caffeine has not been identified as a risk factor. Even so, potential health problems associated with caffeine consumption have to be considered in the con- text of other behaviors. For example, caffeine consump- tion is highly associated with cigarette smoking. Therefore, increased rates of coronary heart disease in heavy coffee drinkers who smoke may be a result of the cigarette smok- ing, not the caffeine consumption (Health Line).26

At the same time, we should be aware that a four- year-old child drinking a 20-ounce cola drink is consum- ing a very high dose of caffeine per body weight, and we should not be surprised to observe marked behavioral and physiological effects.

Osteoporosis and Bone Fractures A 1990 study analyzing caffeine consumption and the incidence of hip fractures among more than three thou- sand elderly men and women found that those who reported drinking 2.5 to 3 cups of caffeinated coffee or 5 to 6 cups of caffeinated tea per day had a 69 percent greater risk of osteoporosis (bone loss and brittleness) than caffeine abstainers. Those who reported drinking more than 3.5 cups of caffeinated coffee or 7 cups of caffein- ated tea had an 82 percent greater risk. Because one of the effects of caffeine is to increase the urinary excretion

TABlE 11.3

Current leading “energy drinks” in the U.S. market

BRANd dOMESTiC MARKET

SHARE (2011) CAFFEiNE

CONTENT (mg) SERviNG

QUANTiTy (oz) CAFFEiNE (mg/oz)*

Red Bull 39.7% 80 8.4 9.6

Monster Energy 20.7% 160 16.0 10.0

Rockstar 7.4% 160 16.0 10.0

NOS 3.7% 260 16.0 16.2

Mega Monster Energy 3.1% 240 24.0 10.0

Note: Some brands also contain taurine, guarana, or bitter orange. All of these ingredients have stimulant properties and have the potential to elevate heart rate and blood pressure. Checking the list of ingredients is a good idea, even though manufacturers are not required to specify the milligram quantities.

*Comparable caffeine content in Coca-Cola Classic is 2.9 mg/oz.

Sources: www.energyfiend.com, 2013. Top energy drink brands, 2011. Market Share Reporter (2012). Detroit: Gale. Business Insights: Essentials. Web. April 2013.

286 ■ Part Three Legal Drugs in Our Society

of calcium and to inhibit the absorption of calcium from the diet in the elderly, it makes sense that there might be an adverse effect on bone tissue in this age group.27

Breast Disease A 1981 report indicated a relationship between caffeine consumption and the formation of benign (that is, non- cancerous) lumps in the breasts called fibrocystic lesions. However, the study was severely criticized as not being based on randomized sampling and as not having meth- odological controls that would shield the researchers from imposing their bias in observing fibrocystic lesion cases. Subsequent studies that were more carefully executed showed no relationship between the incidence of this fre- quently painful condition and caffeine consumption.28

Effects during Pregnancy and Breastfeeding At one time, caffeine use was suspected to be linked to infertility in women. A study in 1990 reported that women who consumed three cups of coffee a day reduced their chances of getting pregnant by 25 percent. More recent studies, however, have found no relation- ship between caffeine intake and infertility.29

Nonetheless, there can be potential problems later in pregnancy. Caffeine consumption (more than three

or four cups of coffee a day) during the first three months of pregnancy is related to a greater incidence of low birth weight in the newborn, although the incidence of premature birth or birth defects is not increased. There is also a relationship between very high levels of caf- feine consumption (more than six cups of coffee per day) during pregnancy and an increased risk of miscar- riage. Therefore, the cautionary advice of the FDA is warranted: Women should abstain from caffeine if at all possible during pregnancy.30

Afterward, in the case of breastfeeding, it is also a good idea to continue a caffeine-free diet. Enzymes that normally break down caffeine in the liver are not present in the liver of a newborn baby, and as a consequence, the elimination half-life of caffeine is much longer than in the adult—up to eighty-five hours. Although there is no evidence of specific harm from having a stimulant such as caffeine in the nervous system for such intervals of time, it seems to be a situation that might well be avoided.31

Panic Attacks Consumption of caffeine equivalent to about four to five cups of coffee a day has been associated with the onset of panic attacks in those individuals suffering from a panic disorder. This finding is consistent with the known effects of caffeine as a CNS stimulant. Any per- son with a history of panic attacks should be careful to

Health Line Coffee, Genes, and Heart Attacks

The known stimulant effect of caffeine on cardiac muscle has raised suspicions about the potential risk of a heart attack due to coffee intake. As described in this chapter, the medical findings are often confusing, and a number of explanations have been advanced to explain contradic- tions in the data.

A major study points to the role of an enzyme that controls the metabolism of caffeine in the body. Research- ers studied 2,000 patients who had suffered heart attacks and 2,000 healthy subjects. Analysis of their DNA revealed a gene sequence that allowed caffeine to break down up to four times more slowly than normally. Individuals with the relatively “slow” version of this gene had an increased risk of a heart attack with as little as two cups of coffee per day. However, those individuals with the relatively “fast” version had no increased risk, even with four or more cups per day. Indeed, for individuals younger than 50 years of

age who had the fast version of the gene, the consumption of one to three cups per day was associated with a lower risk. In other words, for this particular group, caffeine had a protective effect with respect to a potential heart attack.

The stimulant effect of caffeine on the nervous system is not related to this particular gene sequence, so whether individuals had the slow or the fast version did not change their behavioral response to coffee. Nonetheless, the increasing attention being paid to genomic variations among individuals is certain to shed light on previously inconclusive medical research concerning the health risks of various orally administered drugs (see Chapter 3).

Source: Cornelis, M. C.; El-Sohemy, A.; Kabagambe, E. K.; and Campos, H. (2006). Coffee, CYP1A2 genotype, and risk of myocardial infarction. Journal of the American Medical Association, 295, 1135–1141.

Chapter 11 Caffeine ■ 287

avoid caffeine, and mental health professionals should be aware of the possibility that caffeine consumption could trigger a panic episode.32

Dependence, Acute Toxicity, and Medical Applications

More than 85 percent of the adult U.S. population con- sume caffeine in one form or another each day. The aver- age daily intake of caffeine among caffeine consumers is about 280 mg, equivalent roughly to three standard cups of coffee. Estimates of daily caffeine intake in Europe and other nations of the world are considerably higher. Clearly, caffeine consumption is a cultural norm in the United States and the rest of the world. The fact that caf- feinated beverages in particular are embedded in the diet of this country makes it difficult to think of caffeine as a drug, much less one that could cause dependence.33

Tolerance When individuals who do not usually use caffeine are administered repeated doses equivalent to amounts that would ordinarily be acquired from the diet, the initial increases in heart rate and blood pressure start to decline after approximately seventy-two hours.34 In other words, with respect to the cardiovascular effects of caffeine, a classic tolerance effect, as defined in Chapter 2, can be observed.

With respect to the behavioral and psychological effects of caffeine, tolerance effects are more difficult to evaluate, despite the fact that most of us have noticed at some time in our lives that caffeine was having a pro- gressively smaller effect on us as we started to be habit- ual caffeine consumers. The problem appears to be that once we are in a laboratory setting, most of us are already tolerant to the effects of caffeine. Recent stud- ies that have specifically controlled for variations in the subject’s recent dietary intake of caffeine have shown tolerance effects for dosage levels as low as 100 mg, the equivalent of one to two cups of coffee.

Withdrawal A stronger case for caffeine being a drug that produces physical dependence comes from research findings con- cerning withdrawal. As you may yourself have experi- enced, a sudden cessation in the intake of coffee or other caffeinated products results in symptoms of headache, impaired concentration, drowsiness, irritability, muscle

aches, and other flu-like symptoms. A headache is a typi- cal withdrawal symptom, usually appearing from twelve to eighteen hours after the last dose of caffeine, peaking over the next two days or so, and persisting in some indi- viduals for up to a week. This pain is associated with an increase in blood flow to the brain, at levels above what a person normally experiences. A reintroduction of caffeine causes the pain and other withdrawal symptoms to disap- pear. One study on the pattern of withdrawal symptoms from coffee found significant symptoms even when sub- jects had been consuming as little as 100 mg per day.35

Craving The case for physical dependence is clear; the case for psychological dependence, however, is presently uncer- tain. We do not know whether the tendency to have that next cup of coffee or other caffeinated product is a mat- ter of desiring to have it or an effort to avoid withdrawal symptoms that would ensue if we did not have it.

Acute Toxicity of Caffeine Too much caffeine can produce toxic effects on the body, but the amount that might do so is substan- tial and generally beyond what we typically consume. Approximately 1,000 mg of caffeine (equivalent to about ten cups of caffeinated coffee), consumed over a short period of time, results in extreme nervousness and agi- tation, muscle hyperactivity and twitching, profound insomnia, heart palpitations and arrhythmias, gastroin- testinal upset, nausea, and diarrhea. The condition is referred to as caffeinism. In a few individuals, particu- larly those who do not typically ingest caffeine, these symptoms might arise from a much lower dose level. There is also growing concern that caffeine use might magnify emotional difficulties in mental health patients and reduce the benefits of medications they are taking.

Caffeinism is not officially recognized as a psycho- logical disorder by the American Psychiatric Association, but the DSM-IV-TR and the newer DSM-5 manuals (see Chapter 2) define a condition called caffeine intoxica- tion, resulting from a caffeine intake in excess of 250 mg and producing caffeinism-like behavioral symptoms. It is admittedly unusual to observe such behaviors from a caffeine level equivalent to two or three cups of coffee, but as the dose rises above this level, the probability of observing a toxic reaction can be expected to increase.36

caffeinism: A dangerous state of behavioral and physiological overstimulation from a very large dose of caffeine.

288 ■ Part Three Legal Drugs in Our Society

The adult lethal dose is approximately 5 to 10 grams (5,000 to 10,000 mg), which is equivalent to somewhere between fifty and one hundred cups of caffeinated cof- fee. The lowest caffeine dose known to have been fatal in an adult is 3.2 grams (3,200 mg), administered mis- takenly by a nurse who believed the syringe contained another drug. A caffeine-induced fatality was reported in 2010 following an intentional ingestion of 10,000 mg. Naturally, lethal doses for children are lower, and a num- ber of accidental deaths have resulted from children eat- ing large quantities of caffeine-containing medications.37

Prescription Drugs Based on Xanthines Owing to the superiority of theophylline over caffeine in its ability to relax smooth muscle, theophylline has been used medically to treat a number of clinical condi- tions. Its application as a bronchodilator for asthmatics has been mentioned earlier. One particular medication, aminophylline, combines theophylline with methyledi- amine, an inert compound that increases the absorption of theophylline and enhances its clinical benefit. Because theophylline also stimulates cardiac muscle, it is some- times prescribed for patients with congestive heart disease.

Caffeine and Young People: A Special Concern

There is little doubt that caffeine consumption among young people in the United States under the age of eigh- teen has risen significantly in the last decade or so. One reason has to do with the consumption of caffeinated soft drinks. It has been estimated that teenagers consume about sixty-four gallons of soft drinks each year, largely in caffeinated forms. Mega-sized soft drinks, sometimes with free refills, are standard offerings in fast-food restaurants and convenience stores; soft-drink vending machines that provide 20-ounce bottles, instead of 12-ounce cans, are not uncommon. You might recall a similar issue in Chapter 8, related to calculating the total amount of alco- hol in a given number of alcoholic “drinks.”

Another major opportunity for caffeine consump- tion in this age group comes from patterns of cof- fee drinking at coffee bars, where highly caffeinated espresso drinks served sweet, cold, and in “grande” quantities are enormously popular. Although the level of caffeine intake in multiple soft drinks and cof- fee may be equivalent to levels experienced by many adults, the physiological and behavioral effects are

actually greater, since body weight in a younger popu- lation is only one-half to two-thirds that of an adult. In other words, the dosage level of caffeine, expressed as milligrams per kilogram (mg/kg), ends up exceeding levels typically ingested by adults (Table 11.3). In some European countries (the United Kingdom, Sweden, and Finland) per capita caffeine consumption among young people exceeds that in the United States.

The extent of caffeine consumption in this popula- tion raises some significant health concerns. Drinking caffeinated beverages instead of milk can result in obe- sity as well as deficient levels of calcium and phospho- rus, minerals that are needed for normal bone growth during adolescence. Although research is presently lacking on the issue of whether significant caffeine consumption in the early years will lead to osteoporo- sis in adulthood, the research showing an increased risk among the elderly suggests that a similar risk might exist for younger people as well. Finally, the evidence is quite clear that soft-drink consumption and the substantial calorie intake associated with it have significant adverse metabolic effects, resulting in obesity and increased risk of Type 2 diabetes. Indeed, soft-drink consumption is widely viewed as a factor in the increased prevalence of childhood obesity in American youths.38

On a behavioral level, there are concerns about insomnia, nervousness, and anxiety among young peo- ple who ingest large amounts of caffeine. On the other hand, some evidence suggests that moderate levels of caffeine consumption may reduce the hyperactivity and impulsiveness associated with attention-deficit/ hyperactivity disorder (ADHD). In this sense, caffeine acts as a CNS stimulant in much the same way as the stronger stimulant medications, such as methylpheni- date (Ritalin) and amphetamine, that are prescribed for this disorder (Chapter 4).39

The large doses of caffeine ingested by young people on a daily basis have raised health concerns.

Chapter 11 Caffeine ■ 289

Drugs . . . in Focus

Energy Shots Highly caffeinated “power drinks” such as Red Bull and Monster Energy, containing an approximate caffeine dos- age of 10 mg per fluid ounce (compared to Coca-Cola Classic at 2.9 mg per fluid ounce), have become a major part of the current soft drink industry market. Recently, a new class of highly concentrated caffeinated products, so- called energy shots, have appeared on the scene, packaged in two-ounce plastic bottles. A major brand, 5-Hour Energy, has been reported to contain about 215 mg of caffeine. Sales in energy drinks in general in 2012 exceeded $10 bil- lion, more than iced tea and sports beverages like Gatorade.

Health and nutrition professionals, however, have great concerns about young people indulging in energy-shot prod- ucts. Although the product manufacturers recommend taking no more than two bottles per day, spaced several hours apart, there are no restrictions on its sale and use by the consumer. There are reports of people taking energy shots combined with alcohol as a new form of club drug. Of particular con- cern is the combination of energy shots with the nonmedical use of stimulant medications such as Adderall (see Chapter 4).

In 2012, the FDA disclosed that it had received reports of 13 deaths over a four-year period that cited the pos- sible involvement of 5-Hour Energy, as well as more than

30 incidences of serious or life-threatening injuries such as heart attacks and convulsions. The reports had been sub- mitted by the manufacturer; since 2008, when products are classified as dietary supplements (as is the case with 5-hour Energy), producers are required to make such reports when they become aware of product-related death or seri- ous injury. Producers of energy drinks marketed as bever- ages (as is the case with Red Bull and similar products) are not required to do so, though they can notify the FDA on a voluntary basis. In 2010, German health authorities issued a statement warning against overconsumption of energy shots and have deemed the products unsafe.

Sources: Energyfiend.com, 2013. Garnier, L. M.; Arria, A. M.; Caldeira, K. M.; Vincent, K. B.; et al. (2009). Nonmedical pre- scription analgesic and concurrent alcohol consumption among college students. American Journal of Drug and Alcohol Abuse, 35, 334–338. Meier, B. (2013, January 2). Energy drinks promise edge, but experts say proof is scant. New York Times, pp. A1, B4. Meier, B. (2012, November 15). Caffeinated drink cited in reports of 13 deaths. New York Times, pp. B1, B10. Neuman, W. (2009, July 11). Little bottle, big punch: “Energy shots” stimulate power drink sales. New York Times, pp. B1, B5. Starling, S. (2010, February 4). Germans call for energy shot ban. Nutra ingredients.com.

Summary

Caffeine ● Caffeine belongs to a family of stimulant drugs called

xanthines. It is found in coffee, tea, chocolate, many soft drinks, and some medications.

● Other xanthines are theophylline (found in tea) and theobromine (found in chocolate).

Coffee ● Coffee drinking originated in the Middle East and

later was introduced to England in the seventeenth century. Coffee houses in Britain and in colonial America sprang up as establishments where political and social discussions could be held.

● On average, a 5-ounce cup of coffee contains roughly 100 mg of caffeine, the actual level being determined

by the type of coffee beans used and the method of brewing.

Tea ● Tea drinking originated in China and later was intro-

duced to Europe by Dutch traders in the early seven- teenth century. It became most popular in Britain and Russia. Today, tea consumption is greatest in Britain and Ireland.

● On average, a 5-ounce cup of tea contains roughly 60 mg of caffeine, the actual level being determined by the method of brewing and brand.

Chocolate ● Chocolate originated in pre-Columbian Central

America and was introduced into Europe by the

290 ■ Part Three Legal Drugs in Our Society

Key Terms

adenosine, p. 283 baking chocolate, p. 280 caffeine, p. 276 caffeinism, p. 287

Camellia sinensis, p. 278 chocolate liquor, p. 280 cocoa bean pods, p. 279 cocoa butter, p. 280

Coffea arabica, p. 277 Coffea robusta, p. 277 theobromine, p. 276 theophylline, p. 276

xanthines, p. 276

Endnotes

1. Austin, G. A. (1978). Perspectives on the history of psycho- active substance use. Rockville, MD: National Institute on Drug Abuse, p. 50. Jacob, H. E. (1935). Coffee: The epic of a commodity. New York: Viking Press, pp. 3–10.

2. Robinson, E. F. (1893). The early history of coffee houses in England. London: Kegan Paul, p. 26. Cited in E. M. Brecher and the editors of Consumer Reports (1972), Licit and illicit drugs. Boston: Little, Brown, p. 197.

3. Ukers, W. H. (1935). All about coffee. New York: Tea and Coffee Trade Journal Co., p. 61. Wellman, F. L. (1961).

Coffee: Botany, cultivation, and utilization. New York: Interscience Publishers, p. 22–23.

4. International Coffee Organization, London, 2013. Pen- dergrast, M. (1999). Uncommon grounds: The history of coffee and how it transformed our world. New York: Basic Books. Starbird, E. A. (1981, March). The bonanza bean: Coffee. National Geographic Magazine, pp. 398–399.

5. Barone, J. J., and Roberts, H. (1984). Human consump- tion of caffeine. In P. B. Dews (Ed.), Caffeine: Perspectives from recent research. Berlin: Springer-Verlag, pp. 60–63.

return of Cortés to Spain in 1528. Its popularity spread across Europe in the seventeenth century. By the 1880s, techniques for producing present-day milk chocolate had been perfected.

● The caffeine level in chocolate is relatively low, roughly 6 mg per ounce.

Soft drinks ● Caffeinated colas have most of the caffeine con-

tent added to the beverage during production. Lev- els of caffeine in these beverages are approximately 34–45 mg per 12 ounces.

● In recent years, a category of highly caffeinated soft- drinks (such as Red Bull and Monster Energy) has entered the market and represents currently the fast- est-growing segment of the beverage industry.

Caffeine from Medications ● Like drugs, caffeine and other xanthines are stimu-

lants of the CNS and of peripheral musculature. Theophylline, in particular, has a strong broncho- dilating effect and is useful for treating asthmatic conditions.

Caffeine as a drug ● The behavioral effects of caffeine can be character-

ized principally as a reduction in fatigue and bore- dom, as well as a delay in the onset of sleep.

● Recent evidence suggests that caffeine might lower the risk of developing Parkinson’s disease in men.

A comparable protective role in women is currently uncertain.

● Health risks from moderate consumption of caffeine are not clinically significant, except for the adverse effects on fetal development during pregnancy, the development of bone loss among the elderly, a possi- ble adverse effect on the cardiac condition of patients already suffering from cardiovascular disease, and the aggravation of panic attacks among patients with this disorder.

● Continued consumption of caffeine produces toler- ance effects; when caffeine consumption ceases, with- drawal symptoms are observed. High levels of caffeine consumption can produce toxic effects, although deaths are extremely rare.

Kids and Caffeine ● Young people in the United States ingest increasingly

large quantities of caffeine through the drinking of caffeinated soft drinks and coffee. The actual dosage level is substantial, since body weight is less than that of an adult.

● Health concerns regarding caffeine consumption in this population include potential deficiencies in calcium and phosphorus for normal bone growth as well as behavioral problems such as insomnia, nervousness, and anxiety. The current popularity of highly caffeinated “energy drinks” has added to these problems.

Chapter 11 Caffeine ■ 291

6. Shalleck, J. (1972). Tea. New York: Viking Press. 7. MacFarlane, A., and MacFarlane, I. (2003). The empire

of tea: The remarkable history of the plant that took over the world. New York: Overlook. Maitland, D. (1982). 5000 years of tea: A pictorial companion. Hong Kong: CFW Publications Limited, pp. 80–89.

8. Gilbert, R. (1986). Caffeine: The most popular stimulant. New York: Chelsea House, p. 23.

9. Grosser, D. S. (1978). A study of caffeine in tea. American Journal of Clinical Nutrition, 31, 1727–1731.

10. Pastore, R. L., and Fratellone, P. (2006). Potential health benefits of green tea (Camellia sinensis): A narrative review. Explore, 2, 531-539. Shah, J. J.; Kuhn, D. J.; and Orlowski, R. Z. (2009). Bortezomib and EGCG: No green tea for you? Blood, 113, 5695-5696. Weinreb, O.; Mandel, S., Amit, T.; and Youdim, M. B. H. (2009). Neurological mechanisms of green tea polyphenols in Alzheimer’s and Parkinson’s diseases. Journal of Nutritional Biochemistry, 2004, 506–516. Yang, C. S.; Lambert, J. D.; and San, S. (2009). Antioxidative and anti-carcinogenic activities of tea polyphenols. Archives of Toxicology, 83, 11-21. Zijp, I. M.; Korver, O.; and Tijberg, L. B. M. (2000). Effect of tea and other dietary factors on iron absorption. Critical Reviews in Food Science and Nutrition, 40, 371–398.

11. Courtesy of the Food and Agriculture Organization (FAO) of the United Nations, 2008.

12. Morton, M., and Morton, F. (1986). Chocolate: An illus- trated history. New York: Crown Publishers, pp. 77–87.

13. Information for 2012 courtesy of the Chocolate Manu- facturers’ Association and the CAOBISCO Secretariat, Brussels.

14. Apgar, J. L., and Tarka, S. M. (1998). Methylzanthine composition and consumption patterns of cocoa and chocolate products. In G. A. Spiller (Ed.), Caffeine. Boca Raton, FL: CRC Press, pp. 163–192. Courtesy of the Hershey Company, Hershey, PA.

15. Noonan, D. (2001, May 14). Red Bull’s good buzz. Newsweek, p. 39. Schwartz, N. D. (2012, August 29). New inquiry into energy drink firms. New York Times, pp. B1, B2. Substance Abuse and Mental Health Services Admin- istration (2011, November 22). Emergency Department visits involving energy drinks. The DAWN Report. Rock- ville, MD: Substance Abuse and Mental Health Services Administration. Warner, M. (2006, March 6). Soda sales are showing their age. New York Times, pp. C1, C6.

16. FDA issues warning letter to makers of AeroShot “caf- feine inhaler.” (2012, March 6). Press Release of the U.S. Food and Drug Administration, Silver Springs, MD. Kuchment, A. (2007, July 30). Make that a double: Our desire for caffeinated “energy” products is soaring. Newsweek, p. 48. Shute, N. (2007, April 23). Over the limit: Americans young and old crave high-octane fuel and doctors are jittery. Newsweek, pp. 60–68. Tumolillo, M. A. (2010, November 17). Company to drop caffeine from alcoholic drinks. New York Times, p. A22.

17. Fredholm, B. B.; Bättig, K.; Homén, J.; Nehlig, A.; and Zvartau, E. E. (1999). Actions of caffeine in the brain

with special reference to factors that contribute to its widespread use. Pharmacological Reviews, 51, 83–133. Gilbert, Caffeine, pp. 76–79. Julien, R. M. (2005). A primer of drug action (10th ed.). New York: Worth, pp. 225–231. Quinlan, P.; Lane, J.; and Aspinall, L. (1997). Effects of hot tea, coffee and water ingestion on physiological responses and mode: The role of caffeine, water, and beverage type. Psychopharmacology, 134, 164–173. Reid, T. R. (2005, January). Caffeine. National Geographic Magazine, pp. 2–32.

18. Davis, A. M.; Zhao, Z.; Stock, H. S.; Mehl, K. A.; et al. (2003). Central nervous system effects of caffeine and adenosine on fatigue. American Journal of Physiology, 53, R399. Schiwall, S. I. (1986, November). Asthma relief that’s brewed by the cup. Prevention, 38, 127. Spiller, G. A. (1998). Basic metabolism and physiological effects of the methylxanthines. In G. A. Spiller (Ed.), Caffeine. Boca Raton, FL: CRC Press, pp. 225–231.

19. Foad, A. J.; Beedie, C. J.; and Coleman, D. A. (2008). Pharmacological and psychological effects of caffeine ingestion in 40-km cycling performance. Medicine and Science in Sports and Exercise, 40, 158–165.

20. Brice, C., and Smith, A. (2001). The effects of caffeine on simulated driving, subjective alertness, and sustained atten- tion. Human Psychopharmacology: Clinical and Experi- mental, 16, 523–531. Lane, J. D., and Phillips-Bute, B. G. (1998). Caffeine deprivation affects vigilance performance and mood. Physiology and Behavior, 65, 171–175. Snel, J.; Lorist, M. M.; and Tieges, Z. (2004). Coffee, caffeine, and cognitive performance. In A. Nehlig (Ed.), Coffee, tea, chocolate, and the brain. Boca Raton, FL: CRC Press, pp. 53–71. Watters, P. A.; Martin, F.; and Schreter, Z. (1997). Caffeine and cognitive performance: The non- linear Yerkes-Dodson Law. Human Psychopharmacology: Clinical and Experimental, 12, 249–257.

21. Curatolo, P., and Robertson, D. (1983). The health con- sequences of caffeine. Annals of Internal Medicine, 98, 641–653. Snel, J.; Lorist, M. M.; and Tieges, Z. (2004). Effects of caffeine on sleep and wakefulness: An update. In A. Nehlig (Ed.), Coffee, tea, chocolate, and the brain. Boca Raton, FL: CRC Press, pp. 13–33.

22. Attwood, A. S. (2012). Caffeinated alcohol beverages: A public health concern. Alcohol and alcoholism, 47, 370–371. Fillmore, M. T.; Roach, E. L.; and Rice, J. T. (2002). Does caffeine counteract alcohol-induced impair- ment? The ironic effects of expectancy. Journal of Studies on Alcohol, 63, 745–754.

23. Ascherio, A.; Chen, H.; Schwarzschild, M. A.; Zhang, S. M.; Colditz, C. A., et al. (2003). Caffeine, postmenopausal estrogen, and risk of Parkinson’s disease. Neurology, 60, 790–795. Santos, C.; Lunet, N.; Azevedo, A.; de Mendoca, A.; Ritchie, K.; et al. (2010). Caffeine intake is associated with a lower risk of cognitive decline: A cohort study from Portugal. Journal of Alzheimer’s Disease, 20, S175–S185. Schwarzschild, M. A., and Ascherio, A. (2004). Caffeine and Parkinson’s disease. In A. Nehlig (Ed.), Coffee, tea, chocolate, and the brain. Boca Raton, FL: CRC Press, pp. 147–163.

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24. Curatolo and Robertson, The health consequences of caffeine. Gierach, G. L.; Freedman, N. D.; Andaya, A.; Hollenbeck, A. R., Park, Y.; et al. (2012). Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort. International Journal of Cancer, 131, 452–460. Michels, K. B.; Willett, W. C.; Fuchs, C. S.; and Giovannucci, E. (2005). Coffee, tea, and caffeine consumption and incidence of colon and rectal cancer. Journal of the National Cancer Institute, 97, 282–292. Ishitani, K.; Lin, J.; Manson, J. E.; Buring, J. E.; and Zhang, S. M. (2008). Caffeine consumption and the risk of breast cancer in a large prospective cohort of women. Archives of Internal Medicine, 168, 2022–2031.

25. Jick, H.; Miettinen, O. S.; Neff, R. K.; Shapiro, S.; Heinonen, O.; et al. (1973). Coffee and myocardial infarction. New England Journal of Medicine, 289, 63–67. Myers, M. G. (1992, November). Caffeine under examination—A passing grade. The Western Journal of Medicine, pp. 586–587.

26. Bonita, J. S.; Mandarano, M.; Shuta, D.; and Vinson, J. (2007). Coffee and cardiovascular disease: In vitro, cellular, animal, and human studies. Pharmacological Research, 55, 187–198. Julien, R. M. (1998). A primer of drug action (8th ed.). New York: Freeman. Quotation on p. 163.

27. Bruce, B., and Spiller, G. A. (1998). Caffeine, calcium, and bone health. In G. A. Spiller (Ed.), Caffeine. Boca Raton, FL: CRC Press, pp. 345–356. Wetmore, C. M.; Ichikawa, L.; LaCroix, A. Z.; Ott, S. M.; and Scholes, D. (2007). Association between caffeine intake and bone mass among young women: Potential effect modification by depot medroxyprogesterone acetate use. Osteoporosis International, 19, 517–529.

28. Levinson, W., and Dunn, P. M. (1986). Nonassociation of caffeine and fibrocystic breast disease. Archives of Internal Medicine, 146, 1773–1775. Minton, J. P.; Foecking, M. K.; Webster, J. T.; and Matthews, R. H. (1979). Caffeine, cyclic nucleotides, and breast diseases. Surgery, 86, 105–109. Russell, L. C. (1989). Caffeine restriction as initial treat- ment for breast pain. Nurse Practitioner, 14, 36–37.

29. Caan, B.; Quesenberry, C. P.; and Coates, A., O. (1998). Differences in fertility associated with caffeinated bever- age consumption. American Journal of Public Health, 88, 270–274. Riduan J. M.; Beral, V.; Rolfs, R. T.; Aral, S. O.; and Cramer, D. W. (1990). Are caffeinated beverages risk factors for delayed conception? Lancet, 335, 136–137.

30. Grady, D. (2008, January 21). Pregnancy problems tied to caffeine. New York Times, p. A10. Savitz, D. A.; Chan, R. L.; Herring, A. H.; Howards, P. P.; and Hartmann, K. E. (2008). Caffeine and miscarriage risk. Epidemiology, 19, 55–62. Weng, X.; Odouli, R.; and Li, D. K (2008). Mater- nal caffeine consumption during pregnancy and the risk of miscarriage: A prospective cohort study. American Journal of Obstetrics and Gynecology, 198, 279e1–279e8.

31. Bakker, R.; Steegers, E.; Obradov, A.; Raat, H.; Hof- man, A.; et al. (2010). Maternal caffeine intake from

coffee and tea, fetal grown, and the risks of adverse birth outcomes: The Generation R Study. American Journal of Clinical Nutrition, 91, 1691-1698. Peck, J. D.; Levi- ton, A.; and Cowan, L. D. (2010). A review of the epide- miologic evidence concerning the reproductive health effects of caffeine consumption: A 2000-2009 update. Food and Chemical Toxicology, 48, 2549–2576.

32. Charney, D. S.; Heniger, G. R.; and Jatlow, P. L. (1985). Increased anxiogenic effects of caffeine in panic disor- ders. Archives of General Psychiatry, 42, 233–243.

33. Juliano, L. M., and Griffiths, R. R. (2004). A critical review of caffeine withdrawal: Empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology, 176, 1–29.

34. Robertson, D.; Wade, D.; Workman, R.; and Woosley, R. L. (1981). Tolerance to the humoral and hemodynamic effects of caffeine in man. Journal of Clinical Investigation, 67, 1111–1117.

35. Nehlig, A. (2004). Dependence upon coffee and caffeine: An update. In A. Nehlig (Ed.), Coffee, tea, chocolate, and the brain. Boca Raton, FL: CRC Press, pp. 133–145. Sigmon, S. C.; Herning, R. L.; Better, W.; Cadet, J. L.; and Griffiths, R. R. (2009). Caffeine withdrawal, acute effects, tolerance, and absence of net beneficial effects of chronic administration: Cerebral blood flow velocity, quantitative EEG, and subjective effects. Psychopharma- cology, 204, 573–585. Stiley, C. L. W.; Griffiths, R. R.; and Cottler, L. B. (2011). Evaluating dependence criteria for caffeine. Journal of Caffeine Research, 1, 219–225.

36. American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders (DSM-IV) (4th ed.). Text Revision. Washington, DC: American Psychiatric Association, p. 232. American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (DSM-5) (5th ed.). Washington, DC: American Psychiatric Association.

37. Gilbert, Caffeine, pp. 108–109. Rudolph, T., and Knud- sen, K. (2001). A case of caffeine poisoning. Acta Anaes- thesiologica Scandinavica, 54, 521–523.

38. Dhingra, R.; Sullivan, L.; Jacques, P. F.; Wang, T. J.; Fox, C. S.; et al. (2007). Soft drink consumption and risk of developing cardiometabolic risk factors and the meta- bolic syndrome in middle-aged adults in the community. Circulation, 116, 480–488.

39. Cordes, H. (1998, April 27). Generation wired. The Nation, pp. 11–16. Heatherley, S. V.; Hancock, K. M. F.; and Rogers, P. J. (2006). Psychostimulant and other effects of caffeine in 9- to 11-year-old children. Journal of Child Psychology and Psychiatry, 47, 135–142. James, J. E.; Kristjansson, A. L., and Sigfusdottir, I. D. (2011). Adoles- cent substance use, sleep, and academic achievement: Evidence of harm due to caffeine. Journal of Adolescence, 34, 665–673. Pollak, C. P., and Bright, D. (2003). Caffeine consumption and weekly sleep patterns in U.S. seventh-, eighth-, and ninth-graders. Pediatrics, 111, 42–46.

293

Have I used steroids? You bet I did. Did steroids make me

a better baseball player? Of course they did. If I had it all

to do over again, would I live a steroid-enriched life? Yes,

I would. Do I have any regrets or qualms about relying on

chemicals to help me hit a baseball so far? To be honest,

no, I don’t.

—José Canseco, Juiced (2005)

. . . .I was immature and I was stupid . . . I blame myself. . . .

I knew we weren’t taking Tic Tacs.

—Alex Rodriguez (2009), On admitting steroid use during the 2001–2003

baseball seasons1

I think she [Pat Maris] was shocked that I called her. I felt

that I needed to do that. They’ve been such great support-

ers of me. She was disappointed, and she has every right

to be. I couldn’t tell her how so sorry I was.

—Mark McGwire (2010), On apologizing to Roger Maris’s widow prior to admitting

steroid use during the 1990s2

After you have completed this chapter, you should have an understanding of

▶ The history of performance- enhancing drugs in sports

▶ How anabolic steroids work

▶ The health risks of steroid abuse

▶ Patterns of steroid abuse

▶ Performance-enhancing nonsteroid hormones

▶ Dietary supplements marketed as performance- enhancing aids

▶ Nonmedical use of stimulant medications in baseball

▶ Present-day drug testing in amateur and professional sports

C h a p t e r

1 2

Part Four

Enhancers and Depressants

Performance- Enhancing Drugs and Drug Testing in Sports

294 ■ Part Four Enhancers and Depressants

For the modern-day athlete in a high-pressure world of competitive sports, running a hundredth of a second faster can mean the difference between an Olympic gold medal and a silver; throwing a javelin a few centimeters farther, lifting a kilogram more, or hit- ting a baseball a few feet farther can make you either the champion or an also-ran. The stakes have never been higher. The winning edge might be a matter of a novel technique in training, a new attitude toward winning, a special diet—or the use of drugs. This chapter focuses on issues surrounding performance-enhancing drugs in the world of sports, with particular attention to the abuse of anabolic steroids. We will also look at the continu- ing efforts by regulatory organizations at both the local and international levels to develop testing procedures to detect the presence of such drugs in the athlete’s body.

The use of performance-enhancing drugs is a con- cern not only among athletes who are in the public eye but also among a growing number of young people who simply want to look better by developing their muscles. The serious dangers in such drug-taking behavior, whether the motivation lies in competitive drive or in personal vanity, are major problems that need to be explored. As we will see, performance-enhancing drugs have been part of competitive sports for a very long time.

Drug-Taking Behavior in Sports

The first recorded athletic competition, the Olympic Games in ancient Greece, is also the place where we find the first recorded use of psychoactive drugs in sports. As early as 300 b.c., Greek athletes ate hallucino- genic mushrooms, either to improve their performance in the competition or to achieve some kind of mystical connection to the gods. Later, Roman gladiators and charioteers used stimulants to sustain themselves longer in competition, even when injured.

By the end of the nineteenth century, world-class athletes were experimenting with a variety of stimulant and depressant drugs, including cocaine, caffeine, alco- hol, nitroglycerine, opioids, strychnine, and amphet- amines. In 1886, while competing in a cross-country race, a Welsh cyclist died of an overdose of a combina- tion of morphine and cocaine (now referred to as a speed- ball), the first drug-related death ever recorded in sports. During the 1904 Olympics, U.S. marathoner Tom Hicks

collapsed after winning the race and lost consciousness. When he was revived, doctors were told that he had taken a potentially lethal mixture of strychnine (a CNS stimu- lant when administered in low doses) and brandy.

With the introduction in the 1930s of anabolic steroid drugs specifically patterned after the male sex hormone testosterone, however, a new element entered the arena of competitive sports. Here was a class of performance-enhancing drugs that did more than alter the behavior or experience of the athlete; these particular drugs actually altered the structure of the athlete’s body.

Anabolic steroid drugs had been studied since the 1930s as a treatment for anemia (low red blood cell count) and for conditions that caused muscles to waste away. Following the end of World War II, steroid drugs were administered to people who were near death from starvation and weight loss. It quickly became apparent, however, that steroids could be useful when given to otherwise healthy individuals as well. As pharmaceuti- cal companies began to introduce dozens of new body- building drugs based on the testosterone molecule, it was natural that information about anabolic steroids would come to the attention of athletes, as well as their coaches and trainers.3

What Are Anabolic Steroids? To understand how testosterone-based steroids pro- duce ergogenic (performance-enhancing) changes, we first have to recognize that testosterone itself has two

by the numbers . . .

46 Percentage of people who believe that Alex Rodriguez was using performance-enhancing drugs for a longer time than he admitted in his 2009 announcement.

25 Highest percentage of Hall of Fame voters approving Mark McGwire for admission into the Baseball Hall of Fame, in four ap- pearances on the ballot. A mini- mum of 75 percent approval is needed for admission.

Sources: Kepner, T. (2010, January 12). McGwire admits steroid use in 1990s, his years of magic. New York Times, pp. B10, B14. Perez, A. J. (2009, February 13). Gallup Poll: Nearly half think A-Rod was doping longer. www.usatoday.com.

ergogenic (ER-go-JEN-ik): Performance-enhancing.

androgenic (AN-droh-JEN-ik): Acting to promote masculinizing changes in the body.

Chapter 12 Performance-Enhancing Drugs and Drug testing in Sports ■ 295

primary effects on the human body. The first and most obvious effect is androgenic (literally, “man-producing”), in that the hormone promotes the development of male sex characteristics. As testosterone levels rise dur- ing puberty, boys acquire an enlarged larynx (resulting in a deeper voice), body hair, and an increase in body size, as well as genital changes that make them sexually mature adults. The second effect is anabolic (upward- changing), in that it promotes the development of protein and, as a result, an increase in muscle tissue. Muscles in men are inherently larger than muscles in women because of the anabolic action of testosterone in the male body.

Steroid drugs based on alterations in the testoster- one molecule are therefore called anabolic-androgenic steroids. Obviously, with respect to performance- enhancement, the goal has been to develop drugs that emphasize the anabolic function while retaining as lit- tle of the androgenic function as possible. For that rea- son, they are most often called simply anabolic steroids. Unfortunately, as we will see, it has not been possible to develop a testosterone-derived drug without at least some androgenic effects (Table 12.1).

It is important that anabolic steroids not be con- fused with adrenocortical steroids, drugs that are patterned after glucocorticoid hormones secreted by the adrenal gland. The major drug of this latter type is hydrocortisone (brand name, among others: Hydro- cortone injection or tablets). The molecular structure of these drugs qualifies them to belong to the steroid family, but there is no relationship to testosterone or any testosterone-like effects. Adrenocortical steroids are useful in the medical treatment of tissue inflam- mation; in sports; they reduce the inflammation asso- ciated with muscle injuries. Their effects on muscle development can be viewed as catabolic (downward- changing), in that they produce a weakening of the muscles, an obviously undesirable option for athletes on a long-term basis.4

Anabolic Steroids at the Modern Olympic Games Steroid use was clearly out in the open during the 1968 Olympic Games in Mexico City. An estimated one-third of the entire U.S. track and field team, not merely the strength-event and field-event competitors but sprinters and middle-distance runners as well, were using ana- bolic steroids. Any controversy over their use, however, did not concern the appropriateness or morality of tak- ing steroids, only which particular steroids worked best.

anabolic (AN-ah-BALL-ik): Acting to promote protein growth and muscle development.

anabolic-androgenic steroids: Drugs that promote masculinizing changes in the body and increase muscle development.

anabolic steroids: Drugs patterned after the testos- terone molecule that promote masculine changes in the body and increased muscle development. The full name is “anabolic-androgenic steroids.”

adrenocortical steroids: A group of hormones se- creted by the adrenal glands. Their anti-inflammatory action makes them useful for treating arthritis and muscle injuries.

TABLE 12.1

Anabolic steroids

TypE of STERoid

GENERic NAmE

BRANd NAmE

Oral danazol Danocrine

drostanolone Masteron

methandrostenolone Dianabol

methyltestosterone Android, Testred, Virilon

oxandrolone Oxandrin, Anavar

oxymetholone* Anadrol

stanozolol Winstrol

Intramuscular nandrolone Deca-Durabolin

injection decanoate IM

nandrolone phenpropionate

Durabolin IM

testosterone proprionate*

Testex IM

testosterone enantrate*

Delatestryl IM

Transdermal patch

testosterone Androderm transdermal system, Testoderm transdermal system

Note: Anabolic steroids are Schedule III controlled sub- stances. As such, they are considered illicit drugs under federal guidelines when not obtained with a medical pre- scription and restricted to medical use along with other Schedule III controlled substances. Several “brand names” marketed for performance-enhancing purposes are combinations of various steroids.

*Approved outside the United States.

Sources: Julien, R. M. (2005). A primer of drug action (10th ed.). New York: Worth, p. 631. National Institute on Drug Abuse (2000, April). Anabolic steroids. Community drug alert bulletin. Bethesda, MD: National Institute on Drug Abuse. Physicians’ desk reference (67th ed.) (2013). Montvale, NJ: PDR Network.

296 ■ Part Four Enhancers and Depressants

Strength-event athletes were taking at least two to five times the therapeutic recommendations (based on the original intent of replacing body protein). The follow- ing year, an editor of Track and Field News dubbed anabolic steroids “the breakfast of champions.” In 1971, one U.S. weight lifter commented, in reference to his Soviet rival,

Last year the only difference between me and him was I couldn’t afford his drug bill. Now I can. When I hit Munich [in 1972] I’ll weigh in at about 340, or maybe 350. Then we’ll see which is better, his ste- roids or mine.5

In the meantime, the notable masculine features of many female athletes from eastern European countries in the 1960s and 1970s, not to mention the number of Olympic records that were suddenly broken, prompted many observers to ask whether they were either men disguised as women or genetic “mistakes.” Questions about the unusually deep voices of East German women swimmers prompted their coach, at one point, to respond, “We came here to swim, not to sing.”

From information that subsequently came to light, we now know that the effects were due to large doses of steroids. Until the late 1980s, the East German govern- ment was conducting a scientific program specifically to develop new steroid formulations that would benefit their national athletes and, at the same time, would be undetectable by standard drug screening procedures. In 2000, the principal physician in the East German Swimming Federation at the time when these steroids were being administered was convicted on charges that from 1975 to 1985 the program caused bodily harm to more than four dozen young female swimmers.6

The 2000 Summer Olympic Games in Sydney, Australia, instituted the strictest drug-testing procedures to date for all competing athletes. For the first time, a specific phrase was inserted into the Olympic Oath, recited by all athletes at the beginning of the games: “. . . committing ourselves to a sport without doping and without drugs.”

In 2004, the World Anti-Doping Code was created. It included an agreed-upon list of prohibited perfor- mance-enhancing drugs and performance-enhancing methods in international sports competitions, testing procedures for their use, and specific penalties for vio- lations. Under the auspices of the World Anti-Doping Agency (WADA), rules and regulations have been for- mally accepted by more than 200 National Olympic Committees, as well as by professional leagues (such as the National Basketball Association and the National Hockey League) representing the United States in the

Olympic Games and other international competitions. The Code has been updated over the years as the devel- opment and availability of new drugs of this kind have changed.

Although the 2012 Olympic Games in London were the first in recent history to report no incidences of performance-enhancing drug use among com- peting athletes, drug-related scandals in sports con- tinue. In 2012, the United States Anti-Doping Agency announced that international cycling champion Lance Armstrong would be banned for life from cycling and stripped of his seven Tour de France titles as well as his bronze medal from the 2000 Olympic Games, after finding that Armstrong had used red-blood-cell booster erythropoietin (EPO), testosterone, corticosteroids and masking agents, as well as engaging in the trafficking of performance-enhancing drugs and participating in a widespread cover-up of doping activities. In 2013, after years of denials, Armstrong admitted using per- formance-enhancing drugs during his cycling career (Portrait).7

Russian pentathlon champion Nadezhda Tkachenko was one of several world-class female athletes in the 1970s who later tested positive for anabolic steroids.

Chapter 12 Performance-Enhancing Drugs and Drug testing in Sports ■ 297

Anabolic Steroids in Professional and Collegiate Sports The widespread use of anabolic steroids in interna- tional athletics in the 1960s quickly filtered down to sports closer to home. Trainers in the National Foot- ball League began to administer anabolic steroids to their players. By the 1970s and 1980s, virtually all the NFL teams were familiar with these drugs. Estimates of how many NFL players were on anabolic steroids var- ied from 50 to 90 percent. We will never know the full extent of the practice, but it was certainly substantial.

Several professional football players remarked at the time that their steroid use had begun while they were playing on collegiate teams, and indeed, football players in several colleges and universities during the 1980s were implicated in steroid use. Football players were not alone in this regard. Use of anabolic steroids had found its way into other collegiate and even high school sports, including track and field, baseball, bas- ketball, gymnastics, lacrosse, swimming, volleyball,

wrestling, and tennis. It is fair to say that until the late 1980s, when screening procedures became common- place, there was no sport, professional or amateur, for which the use of anabolic steroids was not an accepted element in athletic training programs.8

Performance-Enhancing Drug Abuse and Baseball

Record-breaking home-run performances in the late 1990s and early 2000s raised suspicions that these achievements in baseball were due not solely to athletic prowess but to some pharmacological assistance as well. Matters were made worse by the fact that major league baseball (MLB) had stood apart from other professional sports in the United States and sports organizations around the world by failing to establish regulatory poli- cies regarding steroid abuse and the use of other perfor- mance-enhancing drugs.

p o R T R A i T Lance Armstrong—From Honor to Dishonor

The athletic and personal re- cord of professional cyclist Lance Armstrong has made him an icon in modern-day sports. He won the Tour de France a record seven consecu- tive times between 1999 and 2005. In 1997, barely a year after his diagnosis of testicular cancer that had spread to his brain and lungs, Armstrong had conquered it through surgery and che- motherapy. He was the founder of the Lance Armstrong Foundation for can- cer support and was instrumental in raising more than 500 million dollars for the cause. By 2009 he had returned to competitive cycling, finishing third in the Tour de France of that year. Armstrong himself referred to his life as a “mythic, perfect story.”

It was in 2012 that it came apart. Shortly after his decision to renew his entry in the triathlon competitions (he had been in triathlon competi- tion earlier in his life), the United States Anti-Doping Agency (USADA) charged Armstrong with a longstand- ing record of having used illicit

performance-enhancing drugs. In other words, the USADA

was charging him with doping. Two months later, the agency imposed a lifetime ban from athletic competition.

Armstrong never appealed the USADA decision that effectively ended his career. Unlike other athletes for whom suspicions of performance- enhancing drug use have made them live only under a shadow of doubt that their achievements were warranted, there would not be an asterisk in the record books for Lance Armstrong; there would be nothing in the official record books to acknowledge his achievements in the first place. The name of the foundation he created would now simply known as the LIVESTRONG Foundation, severing all ties to Armstrong. Nonetheless, for a time, Armstrong continued to deny the accusations against him, as he had done through most of his career.

In January of 2013, on a televised interview, Oprah Winfrey asked Armstrong whether he had used during

his cycling career performance- enhancing drugs and blood-transfusions (specifically prohibited in competitive sports since 2000). He replied with a simple “yes.” What followed was a series of measured responses. No details were revealed, no names of teammates or other sports associates were mentioned, nor did he elaborate on the ways he had managed through his career to evade the authorities.

After years of denial, Armstrong’s less-than-complete confession of guilt has been viewed as too little and too late. He is a persona non grata in the world of sports, and he faces the possi- bility of major lawsuits from the inves- tors in his professional cycling team. It is unclear where it will end.

Sources: Austin, I. (2013, January 19). Armstrong’s critics largely unmoved by interview. New York Times, p. D2. Macur, J. (2013, January 20). As Armstrong decides next move, agencies are watching. New York Times, p. SP4.

298 ■ Part Four Enhancers and Depressants

In 2004, a prominent track coach, two executives of BALCO, a nutritional supplements laboratory in California, and the personal trainer for outfielder Barry Bonds were indicted on charges of illegally distribut- ing steroids and other performance-enhancing drugs to dozens of professional athletes in baseball and other sports. In a subsequent development, a New York Mets clubhouse assistant pleaded guilty to having supplied performance-enhancing drugs to dozens of current and former major MLB players and their associates between 1995 and 2005, and subsequently laundering the pro- ceeds from these transactions.

Under intense pressure from public opinion and from government officials, the MLB players union

agreed in early 2005 to a policy of steroid testing that was more in line with those of the National Football League and the National Basketball Association. In late 2005, MLB penalties for steroid use were stiffened. Testing procedures and penalties for the use of amphetamine and other stimulants, which had been omitted from consideration in the earlier agreement, were added and later extended to minor league players (see Drugs . . . in Focus).

D e s p i t e c h a n g e s i n p o l i c y w i t h r e g a r d t o performance-enhancing drugs in MLB baseball, it became evident that these kinds of abuses had not ended. In 2007, a major investigation under the direc- tion of former U.S. senator and federal prosecutor

Drugs . . . in Focus

Suspension Penalties for Performance-Enhancing Drug Use in Sports The 2005 agreement on regulations against performance-enhancing drug use in major league baseball (MLB) included a ban on “all substances regarded now, or in the future, by the federal government as steroids” as well as human growth hormone and steroid precursor hormones such as androstenedione. Suspension penalties for positive-test infractions under these new regulations are shown in comparison to previous MLB regulations and those of other U.S. and interna- tional athletic organizations. In 2013, MLB announced an expansion of their drug-testing program, with players required to undergo in-season (as opposed to spring-training and off-season) blood testing for human growth hormone as well as a new test for synthetic testosterone.

Positive test

First Second Third Fourth Fifth Major League Baseball Pre-2005 counseling 15 days 25 days 50 days 1 year Late 2005 50 games 100 games lifetime suspension, with

right of reinstatement after two years

Minor League Baseball 15 days 30 days 60 days 1 year lifetime National Football League 4 games 6 games 1 year 1 year 1 year National Basketball Association 5 games 10 games 25 games 25 games 25 games National Hockey League —no testing for steroids— World Anti-Doping Association (Olympic sports)

2 years

lifetime

Sources: Curry, J. (2006, November 16). Baseball lacks stiffer penalties for steroid use. New York Times, pp. A1, D2. Schmidt, M. S. (2013, January 13). Baseball to expand drug-testing program. New York Times, pp. B13, B17. Schmidt, M. S. (2010, February 24). Baseball plans to start testing for human growth hormone in minors. New York Times, p. B11. NFL will ban amphetamines as enhancers (2006, June 28). Newsday, p. A53.

Chapter 12 Performance-Enhancing Drugs and Drug testing in Sports ■ 299

George J. Mitchell concluded that MLB policies had reduced the use of steroids but that other, nonsteroid performance-enhancing drugs, particularly human growth hormone, had increased in popularity and were widely used. In 2011, Barry Bonds was convicted of one felony count of obstruction of justice in connec- tion with BALCO investigations, although acquitted of charges of perjury. In 2012, pitcher Roger Clemens was found not guilty of lying to Congress in 2008, when he testified that he never administered performance- enhancing drugs during his baseball career. Whether there will be future high-profile trials of this type remains to be seen.9

The Hazards of Anabolic Steroids

One of the problems in evaluating the adverse effects of steroid abuse is that the dosage levels can vary over an enormous range. Since nonmedical steroid use is illegal, it is virtually impossible to know the exact dos- age levels or even the exact combinations of steroids a particular individual may be taking. It is estimated that a “typical” body builder on anabolic steroids takes in a minimum of five to twenty-nine times the therapeutic doses recommended for the medical use of these drugs, but in some cases, the estimates have gone as high as

a hundred to a thousand times the recommended ther- apeutic dose.10

Effects on Hormonal Systems At these huge dosages, anabolic steroids are literally flooding into the body, upsetting the delicate balance of hormones and other chemicals that are normally con- trolled by testosterone. The primary effect in men is for the testes gland to react to the newly increased testoster- one levels in the blood by producing less testosterone on its own. In other words, the gland is getting the incor- rect message that its services are no longer needed. As a result, the testicles shrink, and a lower sperm count leads to sterility, reversible for most men but irrevers- ible in a small number of cases. Paradoxically, the male breasts enlarge (a condition called gynecomastia) because steroids break down eventually into estradiol, the female sex hormone. Other related consequences include frequent, sustained, and often painful penile erections (a condition called priapism) and an enlarge- ment of the prostate gland. Severe acne, particularly on the shoulders and back, results from an increase in the secretions of the sebaceous glands in the skin. Other testosterone-related effects include two changes in hair growth patterns: increased facial hair growth and accel- erated balding on the top of the head.

Some athletes have attempted to counter these undesirable hormonal effects by combining anabolic steroids with human chorionic gonadotropin (HCG), a hormone that ordinarily stimulates the testes to secrete testosterone. In theory, this strategy can work, but the dosages have to be carefully controlled, something that self-medicating athletes are unlikely to do. Repeated HCG treatments actually can have the opposite effect from the one that is intended, making matters worse rather than better. In addition, HCG itself has its own adverse effects, including headaches, mood swings, depression, and retention of fluids.11

Among women taking anabolic steroids, the dra- matically increased levels of testosterone in bodies that normally have only trace amounts produce major physi- ological changes, only some of which return to normal when steroids are withdrawn. Table 12.2 lists the major reversible and irreversible effects among women.

gynecomastia (GUy-neh-coh-mAST-ee-ah): An enlargement of the breasts.

priapism (pRy-ah-pih-zem): A condition marked by persistent and frequently painful penile erections.

Fans expressed their opinion on steroid use at Major League Baseball’s All-Star Game in 2002. Between 5 and 7 percent of MLB players tested positive for anabolic steroids when ran- domized screening was conducted during spring training in 2003. Players involved in steroid use have been dubbed “the syringe generation.”

300 ■ Part Four Enhancers and Depressants

Effects on Other Systems of the Body Given the fact that the liver is the primary mechanism for clearing drugs from the body (see Chapter 3), it is

not surprising that large doses of anabolic steroids take their toll on this organ. The principal result is a greatly increased risk of developing liver tumors. The type of liver tumors that are frequently seen in these circum- stances are benign (noncancerous) blood-filled cysts, with the potential for causing liver failure. In addition, a rupture in these cysts can produce abdominal bleeding, requiring life-saving emergency treatment. Fortunately, these liver abnormalities are reversible when steroids are withdrawn from use.

There is evidence from animal studies that increased steroid levels in the body can produce high blood pressure and high cholesterol levels, as well as heart abnormalities. In human studies, chronic steroid abuse has been associated with an increased risk of cardiovascular disease. There are documented cases of heart-related sudden death among athletes who have been steroid users, even though there was no history of illness or any family history that would predispose them to heart trouble. Cardiac abnormalities such as enlarge- ment of the left ventricle are not reversible when steroid use is discontinued.12

Psychological Problems Stories abound of mood swings and increased aggres- siveness, often referred to by athletes as ‘roid rage, when taking anabolic steroids. Numerous anecdotal reports force us to consider the possibility that real psychologi- cal changes are going on.13

Beyond the well-publicized anecdotal reports, however, more rigorous laboratory investigations into the relationship between anabolic steroid use and psy- chological problems are needed to provide a better understanding of the phenomenon. In a major study addressing this issue, a group of male volunteers were randomly administered intramuscular injections of either testosterone cyprionate or a placebo over a period of twenty-five weeks. All of them were screened for cur- rent or prior psychological problems. One subgroup was engaged in weight training but had no prior history of steroid use. A second subgroup had no training experi- ence and had not used steroids. A third group reported a history of steroid use but had refrained from any use for a minimum of three months prior to the beginning of the study.

The results showed that, on average, testosterone significantly increased manic behavior and feelings of aggressiveness, but the individual reactions were quite variable. Only eight of the fifty men in the study showed any mood changes at all. Two of them showed marked symptoms. One of these men experienced an aggressive

Whether or not aided by performance-enhancing drugs, massive development of musculature continues to be a prized asset in competitive bodybuilding.

TABLE 12.2

Reported side effects of anabolic steroids in ten women

EffEcT

NUmBER REpoRTiNG ThE EffEcT

REvERSiBLE AfTER ENd of USE

Lower voice 10 no

Increased facial hair 9 no

Enlarged clitoris 8 no

Increased aggressiveness 8 yes

Increased appetite 8 unknown

Decreased body fat 8 unknown

Diminished or stopped menstruation

7 yes

Increased sexual drive 6 yes

Increased acne 6 yes

Decreased breast size 5 unknown

Increased body hair 5 no

Increased loss of scalp hair 2 no

Note: The ten women were all weight-trained athletes.

Sources: Strauss, R. H., and Yesalis, C. E. (1993). Additional effects of anabolic steroids in women. In C. E. Yesalis (Ed.), Anabolic steroids in sport and exercise. Champaign, IL: Human Kinetics Publishers, pp. 151–160. Strauss, R. H.; Ligget, M. T.; and Lanese R. R. (1985). Anabolic steroid use and perceived effects in ten weight-trained women athletes. Journal of the American Medical Association, 253, 2871–2873.

Chapter 12 Performance-Enhancing Drugs and Drug testing in Sports ■ 301

outburst at work and, on one occasion, reacted to being cut off in traffic by following the person in his car for several miles. The other man developed extreme eupho- ria and reported a decreased need for sleep. Six other study participants showed more moderate changes. One man in this category found himself wanting to beat up his opponent in a college sports competition, even though he had never had such aggressive feelings before in the course of a game. All of the other participants in the study showed minimal or no effects, and in no case was there an incident of actual violent behavior. Nei- ther previous steroid use nor regular weight training was associated with the symptoms observed in the men responding to testosterone.

Because the study used a double-blind design, nei- ther the experimenters nor the men being studied knew whether they were being injected with testosterone or a placebo (see Chapter 3); half of the men started with the active drug condition, and half started with the pla- cebo condition. Therefore, in interpreting the results, we can eliminate any possible influences of expecta- tions and preconceptions about what different behaviors and experiences might result from anabolic steroids. On the basis of this information, mood changes and aggres- siveness seem genuinely to result from an elevation in testosterone levels, although the reactions of people tak- ing anabolic steroids are far from uniform. It has been estimated, by extrapolating from the available research literature, that somewhere between 2 and 20 percent of men will develop mood-related psychological problems from anabolic steroid use.

However, it is important to realize that experimen- tal studies underestimate the extent of the phenomenon in the real world. In the study reported here, the maxi- mum dosage of testosterone was 600 mg per week. In actual practice, steroid abusers often take drugs that boost testosterone to as much as 1,000 to 1,500 mg per week—levels that far exceed those that can be safely studied in the laboratory. As a consequence, the per- centage of individuals developing significant mood changes and behavioral problems is likely to be much higher, and the changes and problems themselves can be expected to be substantially greater.14

Special Problems for Adolescents During puberty, a particularly crucial process among boys is growth of the long bones of the body, which results in an increase in height. Anabolic steroids sup- press growth hormones; as a result, muscular develop- ment is enhanced but overall body growth is stunted. Among girls, testosterone-related drugs delay the onset

of puberty, making the body shorter, lighter, and more “girl-like,” while enhancing the user’s overall strength. On a psychological level, feelings of euphoria and aggression that adolescents experience while using anabolic steroids can be replaced by lethargy, loss of confidence, and depression when these drugs are discontinued.15

Patterns of Anabolic Steroid Abuse

In 1990, as a response to increasing awareness of the abuse of anabolic steroids both in and outside of competitive sports, Congress passed the Anabolic Steroid Control Act, reclassifying anabolic steroids as Schedule III controlled substances. Jurisdiction was transferred from the Food and Drug Administra- tion (FDA) to the Drug Enforcement Administration (DEA). As a result of this legislation, pharmacies are permitted to fill anabolic-steroid prescriptions only up to a maximum of five times. Penalties for violating the law can result in a five-year prison term and a $250,000 fine for illegal nonmedical sales, and a one-year term and a $1,000 fine for nonmedical possession. Penalties are doubled for repeated offenses or for selling these drugs to minors. States are permitted to draft their own

Quick Concept Check 12.1

Understanding the Effects of Anabolic Steroids Check your understanding of the effects of anabolic steroids by indicating whether the following conditions can be attributed to steroid use.

1. severe acne on the lower extremities of the body

2. increased aggressiveness and mood swings

3. premature balding in men

4. increased development of the testicles

5. enlarged breasts (gynecomastia) among women

6. accelerated growth in adolescents around the time of puberty

Answers: 1. no 2. yes 3. yes 4. no 5. no 6. no

302 ■ Part Four Enhancers and Depressants

laws regarding the definition of anabolic steroids and to set sentencing guidelines for steroid offenders. Although most states follow the federally mandated Schedule III classification, New York lists steroids in Schedule II, while other states have their own classification systems. In some states, possession of small quantities of steroids is regarded as a misdemeanor; other states regard it as a felony. In most but not all states, first-time offenses do not result in imprisonment, unless there are aggravating circumstances, such as possession of large quantities or evidence of intent to sell or distribute the drugs.16

Despite the regulations now in effect, steroid abuse today remains a major problem. Steroid distribution has become an enormous black-market enterprise. With their use commonly referred to as being “on the juice,” these drugs are channeled principally through people associated with body-building gyms and through Inter- net web sites that frequently change a company’s name and location in an effort to stay one step ahead of the law. Some Internet-based suppliers include a warning on their web sites, “Due to their profound effects and poten- cies, it is recommended to seek the guidance of a phy- sician prior to use,” to protect themselves from liability, although few if any customers would voluntarily divulge their steroid abuse, much less seek medical guidance.

It is estimated that the illicit anabolic steroid market is valued at between $300 million and $400 million each year, and the drugs are smuggled into the United States from Europe, Canada, and Mexico. In 2011, the Uni- versity of Michigan survey reported that between 1 and 2 percent of eighth graders, tenth graders, and high school seniors had used anabolic steroids in their lifetime.17

The Potential for Steroid Dependence Some anabolic steroids can be taken orally and others through intramuscular injections, but abusers often administer a combination of both types in a practice called stacking. Hard-core abusers may take a com- bination of three to five different pills and injectables simultaneously, or they may consume any steroid that is available (“shotgunning”), with the total exceeding a dozen. In addition to the complications that result

from so many different types of steroids being taken at the same time, multiple injections into the buttocks or thighs, with 1.5-inch needles (called “darts” or “points”), are painful and inevitably leave scars. If these needles are shared, as they frequently are, the risk of hepatitis or HIV contamination is significant.

Steroid abusers often follow a pattern called cycling, in which steroids are taken for periods lasting from four to eighteen weeks, the “on” periods being separated by “off” periods of abstinence. Unfortunately, when the drugs are withdrawn, the newly developed muscles tend to “shrink up,” throwing the abuser into a panic that his or her body is losing the gains that have been achieved. In addition, abstinence from steroids can lead to signs of depression, such as problems sleeping, lack of appetite, and general moodiness. All these effects encourage a return to ste- roids, frequently in even larger doses, and generate a crav- ing for the euphoria that the person felt while on them.

A variation of the cycling pattern is the practice of pyramiding. An individual starts with low doses of ste- roids, gradually increases the doses over several weeks prior to an athletic competition, and then tapers off entirely before the competition itself in an attempt to escape detection during drug testing. However, pyra- miding leads to the same problems during abstinence and withdrawal as cycling, except that the symptoms occur during the competition itself.

A major problem associated with steroid abuse is the potential for an individual to believe that his or her physique will forever be imperfect. In a kind of “reverse anorexia” that has been called muscle dysmorphia, some body builders continue to see their bodies as weak and small when they look at themselves in the mirror, despite their greatly enhanced physical development. Peer pressure at the gyms and clubs is a factor in never being satisfied with the size of one’s muscles, but it is becoming apparent that societal pressures play a role as well. In the case of males, it is interesting to examine the evolution of the design of G.I. Joe action figures over the years, from the original toy introduced in 1964 to the most recent incarnation introduced in 1998 (Figure 12.1). Just as the Barbie doll has been criticized as setting an impossible ideal for the female body among girls, male- oriented action figures can be criticized on the same basis for boys.18

Traditional estimates of substance dependence among steroid users range from 13 to 18 percent, but more recent studies indicate that the prevalence rate may be somewhat higher. In an Internet survey, about one in four weight lifters and body builders using ste- roids have reported that they were taking larger amounts of steroids over a longer period of time than originally

muscle dysmorphia (dis-moRf-ee-ah): The per- ception of one’s own body as small and weak and of one’s musculature as inadequately developed, despite evidence to the contrary. Also known as meg- orexia, the condition of muscle dysmorphia is a form of body dysmorphic disorder.

Chapter 12 Performance-Enhancing Drugs and Drug testing in Sports ■ 303

intended, that they needed increased amounts of ste- roids to achieve the desired effect, or that they experi- enced physical or emotional problems when steroids were discontinued. One in eight admitted that they had resumed steroid use to relieve a problem that occurred when they stopped (Health Alert). About one-third of them met the criteria for substance dependence, accord- ing to DSM-IV guidelines (see Chapter 2).19

In light of the potential for steroid dependence and the adverse effects of acute steroid use, prevention pro- grams have been instituted to address the problems of ste- roid abuse, particularly among male adolescents involved in sports. The most prominent example, developed by Linn Goldberg at Oregon Health and Science Univer- sity at Portland, is called the Adolescents Training and Learning to Avoid Steroids (ATLAS) program. Young athletes, team coaches, and team captains receive instruc- tion on both sides of the issue—the desirable effects as well as the adverse effects of steroid use. This approach is taken because a failure to acknowledge potential benefits reduces the credibility of the intervention.

Evaluations of the ATLAS program have shown that program participants were better informed than a control group about proper exercise, had a better understanding of the harmful effects of steroids, devel- oped a more negative attitude toward others who used steroids, and were more likely to engage in healthful eating habits. They also showed a 53 percent reduction in new use of anabolic steroids after one year, as well as a 63 percent reduction in the intention to use these drugs in the future. Another prevention and education program originating at the Oregon Health and Science

University called Athletes Targeting Healthy Exercise and Nutrition Alternatives (ATHENA), is specifically oriented toward female athletes, addressing issues such as the connection between disordered eating behaviors and use of body-shaping and performance-enhancing drugs. The program promotes healthful sports nutrition and strength-training alternatives, as well as the training needed to make healthy choices in sports and through- out their lives.20

Counterfeit Steroids and the Placebo Effect As with many illicit drugs, some products marketed to look like anabolic steroids are not the real thing. The problem here is that athletes are notoriously supersti- tious and easily leave themselves open to placebo effects. On the one hand, in the case of anabolic steroids, the effects on muscle development are usually so dramatic that it is difficult to mistake the response as simply a result of a placebo effect. On the other hand, some per- formance-enhancing drugs have far more subtle effects, and psychological factors can end up playing a greater role. In relating his own experience with steroids, MLB superstar Alex Rodriguez spoke of the placebo effect:

I’m not sure what the benefit was. . . . I will say this: when you take any substance, especially in baseball, it’s half mental and half physical. If you take this glass of water and say you’re going to be a better baseball player, if you believe it, you probably will be. I certainly felt more energy, but it’s hard to say.21

1974 1994 MARK MCGWIRE

BICEPS CIRCUMFERENCE EXTRAPOLATED

TO A 6-FOOT MAN

A decade later, Joe was bulked up and given a "kung- fu grip."

The original G.I Joe from 1964 had relatively normal proportions.

Hall of Fame series

Gung-Ho, the ultimate marine, had a Marine Corps tattoo.

15.2 INCHES

12.2 INCHES

16.4 INCHES

20.0 INCHES

Sources: "The G.I. Joe Encyclopedia," by Vincent Santelmo; Photographs by Vincent Santelmo (G.I. Joes, except far right) and Associated Press (Mark McGwire).

N.Y. Times News Service

1964 First G.I. Joe released

1998 26.8 INCHES

The latest incarnation is the aptly named G.I. Joe Extreme.

Even at 6'5", Mark McGwire, the homerun king, is no match for the latest incarnation of Joe.

f i G U R E 1 2 . 1

The muscle development of the G.I. Joe action figure has increased dramatically since its introduction in 1964. The estimated bcep circumference for a six-foot man, based on dimensions of the action figure, more than doubled from 1964 to 1998.

Source: GI Joe figures courtesy of Vincent Santelmo from his book The Complete Encyclopedia of GI Joe, (3rd ed.) August 2001. Photo of Mark McGwire © Getty Images.

304 ■ Part Four Enhancers and Depressants

Nonsteroid Hormones and Performance-Enhancing Supplements

Certainly anabolic steroids have dominated the perfor- mance-enhancing drug scene, but other products have been promoted as having performance-enhancing prop- erties. They include human growth hormone, andro- stenedione, and creatine.

Human Growth Hormone One illicit alternative, human growth hormone (hGH), has become increasingly popular, according

to experts in this field, because it is more widely avail- able and cheaper than in previous years, in contrast to the ever more costly illicit steroids. Those who take this pituitary hormone, however, face the increased risk of developing a significant side effect called acromegaly, a condition resulting in a coarse and misshapen head, enlarged hands and feet, and damage to various inter- nal organs.

Prior to 1985, hGH was obtained from the pituitary glands of human cadavers, but now genetically engi- neered hGH (brand names: Protropin and Humatrope) is available, having been approved by the FDA for the treatment of rare cases of stunted growth in children. Although the distribution of these drugs is controlled by their manufacturers as carefully as possible, supplies manage to get diverted for illicit use.

Testimony in 2008 that prominent major league baseball players had used hGH for performance- enhancing purposes revealed the abuse potential of this hormone in professional sports. It is doubtful, how- ever, that its reputation for performance enhancement is justified, according to a major review of more than forty studies of hGH in healthy athletes, conducted

human growth hormone (hGh): A naturally occur- ring hormone promoting growth, particularly in the long bones of the body.

acromegaly (A-kroh-mEG-ah-lee): A condition result- ing in structural abnormalities of the head, hands, and feet, as well as damage to internal organs.

h E A L T h A L E R T !

The Symptoms of Steroid Abuse For Both Sexes 1. Rapid increases in strength and/or size beyond what

you would expect in a relatively short time. Putting on ten to twenty pounds of solid muscle within a period of a few weeks or so should be a major warning.

2. Involvement in activities in which steroid abuse is known to be condoned or encouraged

3. Sudden increases in appetite and preoccupation with changes in one’s physical condition

4. Recent appearance of acne, particularly on the upper back, shoulders, and arms

5. Premature male-pattern baldness, including a rapidly receding hairline or loss of hair from the top rear of the head

6. A puffy appearance in the face, as if the individual is retaining water

7. An increase in moodiness or unusual shifts in mood 8. A reddening of the face, neck, and upper chest,

appearing as if one is constantly flushed 9. A yellowing of the skin or the whites of the eyes,

stemming from a disturbance in liver function

For Men 1. An enlargement of the breasts, often accompanied by

protruding nipples 2. An increase in sexual interest and a tendency to

display that interest more aggressively

For Women 1. A lowering of the vocal range 2. Smaller or flatter breasts (see Table 12.1)

Where to go for assistance: www.nida.nih.gov/Infofacts/Steroids.html www.steroidabuse.gov

The National Institute on Drug Abuse sponsors a vast array of web sites related to drug use and abuse. The first web site on steroid abuse includes a comprehen- sive list of potential adverse effects of anabolic steroids; the second web site emphasizes issues of prevention and education.

Source: Wright, J. E., and Cowart, V. S. (1990). Anabolic steroids: Altered states. Carmel, IN: Benchmark, pp. 71–91.

Chapter 12 Performance-Enhancing Drugs and Drug testing in Sports ■ 305

between 1966 and 2007. The conclusion is that hGH use increases lean body mass, but the increased bulk does not raise levels of strength or endurance. Indeed, hGH produces higher levels of lactate in muscle tissue, leading to fatigue; hGH users are more likely than oth- ers to develop joint pain and carpal tunnel syndrome. In the absence of scientific evidence of any performance- enhancing effects, it has been suggested that reports by athletes that hGH helped to increase their athletic per- formance are probably due to a placebo effect. None- theless, despite hGH’s dubious value, hGH screening, capable of differentiating naturally produced hGH from synthetic hGH, became a fixture of drug testing at the 2008 Summer Olympic Games in Beijing. Because hGH has a relatively short half-life, athletes tested posi- tive only if the drug had been injected in the previous twelve to twenty-four hours. No major hGH-related scandals occurred in the 2010 Winter Olympic Games in Vancouver, although, with the number of urine and blood tests exceeding 2,000, it will take up to eight years to determine whether any participating athlete violated anti-doping regulations.22

Dietary Supplements as Performance-Enhancing Aids As recently as ten to twenty years ago, fitness-oriented young people might have taken only basic vitamins and minerals to help them build muscle mass or improve cardiovascular performance. Today, the fitness market is inundated with a growing number of dietary supplement products with presumed performance-enhancing prop- erties; sales of such products exceed $2 billion each year in the United States. They are sold under short, appeal- ing names such as Adenergy and Lean Stack, alongside impressive before-and-after photographs or under long, pseudoscientific names like Vaso XP Xtreme Vasodila- tor and Xenadrine-NRG that are accompanied by com- plex molecular diagrams.23

A prominent example of a dietary supplement used for performance-enhancing purposes is androstenedione. Technically, androstenedione is not an anabolic steroid because it is not based on the specific structure of tes- tosterone itself. Nonetheless, it is testosterone-related because it is a naturally occurring metabolic precursor to testosterone. In other words, the body converts andro- stenedione to testosterone via the action of specific enzymes in the liver. At the recommended daily dose of 300 mg, androstenedione has been found to increase testosterone levels by an average of 34 percent above normal. Despite the increase in testosterone, however, no change in body composition or strength is observed when its effect is compared to that of placebo controls.

There is no evidence that androstenedione promotes muscle protein synthesis at these dosage levels.24 Andro- stenedione rose to prominence in the late 1990s when it became public that St. Louis Cardinals baseball player Mark McGwire had been taking the supplement dur- ing his phenomenal 1998 hitting season (seventy home runs, far eclipsing the previous record). A storm of con- troversy ensued, with some commentators suggesting that McGwire’s record be disallowed because of his androstenedione use. Although it had been banned by the National Football League and other professional and amateur sports organizations, androstenedione had not yet been banned in major league baseball at that time, so McGwire’s use of it was not illegal. The pub- licity surrounding McGwire’s use of androstenedione and its easy availability were blamed for a 30 percent increase among eighth-grade boys and a 75 percent increase among tenth-grade boys in the use of anabolic steroids from 1998 to 2000.

In 2005, the FDA banned the over-the-counter sale of androstenedione (Andro) and other testosterone pre- cursors. By this time, the Anabolic Steroid Control Act of 2004 had expanded the Schedule III classification (see Chapter 2) to include androstenedione and other testosterone precursors, along with anabolic steroids themselves. In early 2010, it was disclosed that andro- stenedione had not been the only performance-enhanc- ing drug in McGwire’s life. He admitted what had been suspected for some time: that during the 1990s he had used anabolic steroids as well. McGwire has denied that his home-run record-breaking achievements could be attributed to steroid use, but it will never be known whether the performance-enhancing drugs he took did indeed enhance his performance.25

Another dietary supplement marketed as a performance-enhancing agent is creatine (brand names: Creatine Fuel, Muscle Power, and many other prod- ucts), a nonprotein amino acid synthesized in the kid- ney, liver, and pancreas from L-arginine, glycine, and L-methionine. Ingestion of creatine has been found to enhance the retention of water by muscle cells, caus- ing them to expand in size. One hypothesis is that water retention might stimulate protein synthesis and increase muscle mass as a result, but there is no evidence from controlled studies that this is the case. Although creatine appears to enhance performance in repetitive bouts of

androstenedione (AN-dro-steen-dyE-own): A dietary supplement, acting as a metabolic precursor to tes- tosterone and used as an ergogenic agent.

creatine (cREE-ah-teen): A dietary supplement avail- able for ergogenic uses.

306 ■ Part Four Enhancers and Depressants

high-intensity cycling and sprints, the weight gain expe- rienced by creatine users makes it undesirable for run- ners or swimmers. Short-term use of creatine has been found to produce muscle cramping, and its long-term adverse effects have not been fully explored.26

Nonmedical Use of Stimulant Medication in Baseball

Earlier in the chapter, we cited nineteenth-century examples of world-class athletes experimenting with stimulants in attempts to achieve some level of perfor- mance enhancement in their sport. More than a cen- tury later, stimulants have continued to be an attractive option. Amphetamines were officially banned from major league baseball in 2005, but before that time, amphetamine use may have been a mainstay for players to stay focused and ward off fatigue in a grueling and lengthy competitive season. According to a professional baseball team psychiatrist, testifying in congressional hearings in 2008, “Amphetamines are the real perfor- mance-enhancing drugs that people should always have been worried about.”

It is therefore not surprising that since 2005, some players have attempted to circumvent the amphet- amine ban by taking stimulant medications intended for the treatment of attention-deficit/hyperactivity dis- order (ADHD). In 2007, 103 therapeutic-use exemp- tions for ADHD were approved for MLB players—a suspiciously high number considering that only 28 players received such approval in 2006. Whether these exemptions reflected a fourfold increase in the incidence of ADHD symptoms over a single year or an effort to benefit from the performance-enhanc- ing effects of stimulant drugs, without violating the amphetamine ban, continues to be a matter of con- cern to MLB management as well as baseball fans (see Point/Counterpoint II, pages 116–117).27

Current Drug-Testing Procedures and Policies

Since the mid-1960s, organizers of major athletic com- petitions have attempted to develop effective screening

procedures to prevent the use of performance-enhanc- ing drugs from giving one competitor an unfair advan- tage over another. Needless to say, these procedures have neither proved perfect nor served as an effective deterrent for drug use among athletes. We are used to hearing about championship events accompanied by reports of an athlete disqualified from competing or denied the honor of winning because he or she tested positive for a particular banned substance. Ironically, the present status of drug testing as a fact of life in mod- ern sports has brought with it a new form of contest, pitting the skill and ingenuity of the laboratory scientist whose job it is to detect the presence of performance- enhancing drugs against the skill and ingenuity of the athlete in devising ways to use them without detection (Drugs . . . in Focus).28

This section looks at drug-testing techniques designed to detect not only performance-enhancing drugs that are relevant to sports but also a wider range of illicit drugs, such as heroin, cocaine, and marijuana. Within some sports organizations, such as the National Collegiate Athletic Association (NCAA), drug tests are conducted not only for the presence of performance- enhancing drugs but also for the presence of drugs that have no particular performance-enhancing benefits. In the case of marijuana, for example, the proper descrip- tion for its effects with regard to athletic competitions might be ergolytic (“performance-reducing”). The pol- icy is defended on the premise that athletes are likely to be exposed to illicit substances, and no collegiate ath- lete should be permitted to compete while engaging in illegal activity. Related issues surrounding drug testing in the general population, particularly in the workplace, will be examined in Chapter 17.

The Forensics of Drug Testing Present-day drug-testing procedures begin with a urine sample from the individual in question. The advantages lie in the ease and noninvasiveness of collecting urine, the ease with which urine can be analyzed for specific factors, and the fact that drugs or their metabolites (by-products) are usually very stable in frozen urine. Therefore, it is possible to provide long-term storage of positive samples, in case the results are disputed. The disadvantages are that many perceive urine collection to be a humiliating experience, a dehydrated athlete may find it difficult to urinate immediately after competing, and there may be ways to tamper with the urine sample prior to testing.

The two major urinalysis methods are the enzyme immunoassay (eiA) technique and a procedure

enzyme immunoassay (EiA): One of the two major drug-testing techniques for detecting banned substances or drugs.

Chapter 12 Performance-Enhancing Drugs and Drug testing in Sports ■ 307

combining gas chromatography and mass spectrom- etry (GC/Ms). In both methods, the collected urine is divided into two samples prior to being sent off to the laboratory so that if the analysis of one sample yields a positive outcome, the analysis can be repeated on the other sample. This reanalysis procedure is often required if an individual appeals the original test result.29

With the EIA method, a separate test must be run on each particular drug that is being screened. First, at an earlier time, the substance to be tested for (THC or

gas chromatography/mass spectrometry (Gc/mS): A drug-testing technique based on the combination of gas chromatography and mass spectrometry.

Drugs . . . in Focus

Pharmaceutical Companies and Anti-Doping Authorities: A New Alliance Through the years of scandals involving performance- enhancing drugs, while the World Anti-Doping Agency (WADA) engaged in a continuing and often frustrating game of “cat and mouse” with competitive athletes, major pharmaceutical companies for the most part remained on the sidelines. Now it appears that they are getting increas- ingly in the game.

A case in point is the medication erythropoietin, marketed in its natural form as Epogen (Amgen Pharma- ceuticals) or in synthetic forms as Aranesp (Amgen) and NeoRecorman (Roche Pharmaceuticals). On the one hand, erythropoietin (also known as EPO) is an effective hormonal treatment for millions of anemia patients who suffer from a deficiency in production of red blood cells in bone marrow. On the other hand, the use of EPO for its performance-enhancing (red blood cell boosting) effect in normal individuals, particularly trained athletes, is clearly a form of cheating, a classic example of “doping.” Prominent headlines regarding accusations and later confirmation of EPO use by world-champion cyclist Lance Armstrong (see Portrait) have been a public-relations problem of sorts for those manufacturing EPO-related drugs. Would the public now associate a valuable medicinal agent with the dark world of doping? Even worse, would some people accuse these companies of developing drugs that could be mis- used by athletes essentially as a way of enhancing sales?

In a major gesture of good “corporate citizenship,” GlaxoSmithKline Pharmaceuticals sponsored the drug- testing laboratories for the 2012 London Summer Olympic Games, carrying the costs for the facilities and the more than 1,000 staff involved in drug screening. It was the first time in Olympic history that an anti-doping operation had a specific corporate sponsor. But the relationship between pharmaceutical companies and international anti-doping

efforts has gone beyond simply the contribution of financial support. Two major manufacturers, Glaxo and Hoffman- LaRoche, are now evaluating every new drug candidate in their development pipeline (see Chapter 14) for potential abuse as a performance-enhancing drug. Customarily, when developing a new drug, a number of reagents are also created in company laboratories that react to the molecular structure of the drug. These reagents remain proprietary compounds, and information about them is kept secret. These particular companies took the unusual step of sharing the reagents with WADA, since it is pre- cisely those reagents that can be “markers” for future drug screening tests.

The actions of Glaxo and Roche are not entirely new. Amgen, for example, was asked by WADA officials to help develop a screening test for Aranesp, released for marketing in 2001, in anticipation of possible doping incidents in the 2002 Salt Lake City Winter Olympic Games. However, not all pharmaceutical companies have been as eager to cooperate with anti-doping authorities in this regard. There remains some reluctance on the part of companies in releasing proprietary information in such a highly competi- tive business as pharmaceuticals. Nonetheless, there is an increasing awareness that the benefits outweigh the costs.

It must be pointed out that performance-enhancing drugs are also being developed in illicit laboratories around the world, having contacts with athletes in nations that have less strict control over doping than the United States. These laboratories work in the shadows of competitive athletics and have little or no incentive to cooperate with WADA or any other anti-doping agency.

Sources: Salyer, K. (2012, July 18). At London Games, a new record for doping tests. BloombergBusinessweek, http://www.businessweek.com/articles/2012-07-18/ at-london-games-a-new-record-for-doping-tests#p2. Thomas, K. (2013, February 19). An unexpected drug reac- tion. Manufacturers increasing join the fight against doping. New York Times, pp. B1, B4.

308 ■ Part Four Enhancers and Depressants

cocaine, for example) has been injected into an ani- mal, eliciting specific immunological antibodies to that substance. The antibodies are then purified into a testing substrate. The combination of the collected urine and the testing substrate will yield a specific reaction if the urine contains the banned substance. A popular commercial testing kit for screening major controlled substances (opi- oids, amphetamines, cocaine, benzodiazepines, and mari- juana), called eMit (enzyme multiplied immunoassay technique), has been marketed by Syva Laboratories, a subsidiary of Syntex Corporation in Palo Alto, California, since the early 1970s. This kit is relatively inexpensive and can be used to screen large numbers of urine samples. It is so widely available that its trademark name, EMIT, is often used to mean any form of EIA method.

With the GC/MS method, the urine is first vapor- ized and combined with an inert gas and then passed over a number of chemically treated columns. Through the process of gas chromatography, technicians are able to identify the presence of a banned substance by the different colorations that are left on the columns. After this has been done, the gas is ionized (converted into an electrically active form) and sent through an electric current and magnetic field that separates out each of the different ions (electrically charged particles) in the gas. Through the process of mass spectrometry, a par- ticular “fingerprint,” or “signature,” of each chemical substance can be detected and measured. The GC/MS technique is considered more definitive than the EIA technique, but it is considerably more expensive and time-consuming. It is also the only testing procedure that adequately screens for anabolic steroids.30

Until the late 1990s, urinalysis was the sole means for drug testing. Since then, however, there has been increasing interest in oral fluid testing. In this proce- dure, a collection pad is placed between the lower cheek and gum for two to five minutes. The collection pad is then sealed and later analyzed by EIA. The sensi- tivity and specificity of the results (see the next section) are comparable to those obtained through urinalysis. As with positive urinalysis tests, a confirmation of positive oral fluid results is made by GC/MS.

Currently available FDA-approved drug-testing sys- tems using oral fluid samples can now provide test results in approximately fifteen minutes. The advantages over traditional urinalysis are obvious. Samples are analyzed on-site rather than having to be sent to laboratories.

Specimen collection can be performed face-to-face (lit- erally) with the donor, with little risk of sample substi- tution, dilution, or adulteration. Embarrassment on the part of the donor is eliminated, as are privacy concerns.31

Sensitivity and Specificity As you might imagine, two general questions can be posed with regard to drug-testing methods.

■ What is the sensitivity of the test? The sensitivity is de- termined by the likelihood that a specimen contain- ing drugs (or drug metabolites) will test positive. This outcome is referred to as a “true positive.” If a drug test has a high degree of sensitivity, then there will be very few “false negatives.” If a test is sensitive, the subject will seldom test negative when drug-taking behavior has actually occurred.

■ What is the specificity of the test? The specificity is de- termined by the likelihood that a drug-free (or drug metabolite-free) specimen will test negative. This out- come is referred to as a “true negative.” If a drug test has a high degree of specificity, then there will be very few “false positives.”

In other words, sensitivity indicates the ability of the test to correctly report the presence of drugs. Specific- ity indicates the ability of the test to correctly report the absence of drugs. In this regard, the GC/MS test is more sensitive and specific than the EIA test.

Frequently, the GC/MS analysis is performed as a confirmation of a positive EIA test. Nonetheless, false positives can occur even with the GC/MS test. Eating a poppy seed roll prior to drug testing or taking quinolone antibiotic medications such as ofloxacin (brand name: Floxin) and ciprofloxacin (brand name: Cipro), for exam- ple, has resulted in false-positive indications of opiate use. Therapeutic levels of ibuprofen (brand names: Advil, Motrin, and Nuprin, among others) have resulted in false-positive indications of marijuana smoking. In addi- tion, the passive inhalation of marijuana smoke can leave sufficient levels of THC metabolites to result in false-pos- itive indications of marijuana smoking, although the den- sity of smoke that needs to be present for this to happen makes it unlikely that individuals would be completely unaware that they were being exposed to marijuana.32

Masking Drugs and Chemical Manipulations Two specific tactics have been employed to disguise the prior use of anabolic steroids so that the outcome of a drug test becomes, in effect, a false negative; both

EmiT (enzyme multiplied immunoassay technique): A commercial testing kit for screening for major controlled substances, based on enzyme immunoas- say analysis.

Chapter 12 Performance-Enhancing Drugs and Drug testing in Sports ■ 309

are now relatively obsolete. The first strategy was to take the anti-gout drug probenecid (brand name: Benemid). Available since 1987, it does mask the presence of ana- bolic steroids, but it is now on the list of banned sub- stances for competitive athletes and is easily detected by GC/MS techniques. The second strategy was to increase the level of epitestosterone in the body. The standard procedure for determining the present or prior use of anabolic steroids is to calculate the ratio of tes- tosterone against the level of epitestosterone, a naturally occurring hormone that is usually stable at relatively low levels in the body. International athletic organiza- tions now use the standard of a 4:1 ratio (formerly 6:1) or higher as indicating steroid use. If epitestosterone is artificially elevated, the ratio can be manipulated down- ward so as to indicate a false-negative result in drug test- ing. However, suspiciously high levels of epitestosterone can now be detected by GC/MS techniques, so this form of manipulation is no longer successful.33

Pinpointing the Time of Drug Use It is important to remember that a positive result in a drug test indicates merely that the test has detected a minimal level of a drug or its metabolite. It is difficult to determine when that drug was introduced into the body or how long the drug-taking behavior continued. In the case of urinalysis testing, the time it takes for the body to get rid of the metabolites of a particular drug varies con- siderably, from a few hours to a few weeks (Table 12.3). In the case of oral-fluid (saliva) drug testing, the window of detection may be different, depending on the drug of interest. Opioids and cocaine are detected within two to three days of ingestion; THC in marijuana is detected within a period ranging from one hour after ingestion to fourteen hours later. Because THC metabolites are excreted into the urine for several days or in some cases for several weeks, oral-fluid testing for marijuana is bet- ter suited for determining when marijuana has been last used. In effect, the “window of detection” is narrower. If the interval between use and testing has been longer than fourteen hours or so but shorter than a few days, urinalysis would pick up a positive result, but oral-fluid testing would not.34

Owing to the expense of randomized drug-testing programs, not every institution can afford the costs. Large corporations may be able to budget for poten- tially thousands of tests for preemployment screening purposes, but relatively few colleges and consider- ably fewer high schools are able to establish the level of funding needed to test their student populations. Even if the costs were lower, it is questionable

whether illicit drug-taking behavior would be reduced in the long run as a result. Interestingly, recent evi- dence indicates that the prospect of randomized drug testing in schools fails to act as a deterrent among students. University of Michigan researchers in 2003 found virtually identical rates of illicit drug use in schools that had drug-testing programs and schools that did not. This general finding was replicated in a study reported in 2008. The deterrent effect of drug testing on illicit drug use in schools clearly has not been demonstrated.35

I t i s a l s o w o r t h c o n s i d e r i n g t h e f o l l o w - ing fact regarding abusers of steroids and related

TABLE 12.3

Detection periods for various drugs in urinalysis testing

dRUG dETEcTioN pERiod

Alcohol 1-12 hours

Amphetamines in general 1-2 hours

Barbiturates

Short-acting 2 days

Long-acting 1-3 weeks

Benzodiazepines

Therapeutic use 3 days

Chronic use (>one year) 4-6 weeks

Cocaine 2-4 days

Marijuana (THC)]

Single use 2-7 days

Chronic, heavy use 1-2 months

MDMA (Ecstasy) 1-2 days

Methamphetamine 1-2 hours

Opioids

Codeine 2 days

Heroin or morphine 2 days

Darvon, Darvocet 6 hours to 2 days

Phencyclidine (PCP)

Casual use 14 days

Chronic, heavy use up to 30 days

Note: The detection periods vary according to the sensitivity of the test or the subject’s physical condition, fluid balance, and state of hydration. Detection periods are relatively longer for hair samples and detection periods are relatively shorter for blood or saliva samples than for urine samples. Detection times for steroids vary from days to months, depending on the steroid and the length of use.

Sources: Drugs of abuse reference guide (2007). Occupa- tional testing services, LabCorp, Research Triangle Park, NC.; Verstraete, A. G. (2004). Detection times of drugs of abuse in blood, urine, and oral fluid. The Drug Monitor, 26, 200–205.

310 ■ Part Four Enhancers and Depressants

performance-enhancing drugs: Individuals who are no longer students in a public institution or partici- pants in an organized athletic program do not need to fear a positive drug test because they will never be required to undergo any form of drug testing, random or otherwise.

The Social Context of Performance-Enhancing Drugs

Anabolic steroids and other performance-enhancing agents are quite different from many of the abused drugs covered in previous chapters in that they affect the way we look and how we compare to others, rather than the way we feel. Charles E. Yesalis, one of the leading experts in steroid abuse, has put it this way:

If you were stranded on a desert island, you might use cocaine if it were available, but nobody would use steroids. On a desert island, nobody cares what you look like and there is nothing to win. We are

the ones who have made the determination that appearance and winning are all important. We’re telling kids in our society that sports is more than a game. Until we change those signals, for the most part, we might as well tell people to get used to drug use.36

Unfortunately, there seems to be little reason to believe that the temptations to indulge in performance- enhancing drugs will go away anytime soon. Numerous surveys taken among young athletes and nonathletes alike indicate that the social signals are crystal clear, and they are more than willing to take up the challenge, despite the risks. Variations of the following question have been asked of them: “If you had a magic drug that was so fantastic that if you took it once you would win every competition you would enter, from the Olympic decathlon to Mr. Universe, for the next five years, but it had one minor drawback—it would kill you five years after you took it—would you still take the drug?” More than half of those polled have answered “yes” to this question.37

There is a more general sense of competition that goes beyond dreams of athletic achievement. It is apparent that an idealized body image is part of today’s

Quick Concept Check 12.2

Understanding Drug Testing Check your understanding of present-day drug-testing results by indicating whether the following statements are true.

1. EIA results are more sensitive than GC/MS results.

£ yes £ no

2. The anti-gout drug probenecid (Benemid) is an effective way of achieving a false-positive result.

£ yes £ no

3. The time of marijuana smok- ing is one conclusion that drug testing has great difficulty in determining.

£ yes £ no

4. Athletes are generally very coop- erative in achieving the least num- ber of false-negative outcomes.

£ yes £ no

5. Anabolic steroid screening is presently mandated by the Inter- national Olympic Committee for winners of Olympic events.

£ yes £ no

Answers: 1. no 2. no 3. yes 4. no 5. yes

The pressure to be number one exists in all areas of athletic competition. The intensity of competition in our culture, how- ever, extends beyond the world of sports. Temptations to se- cure a competitive edge in the corporate world have led to a growing and disturbing acceptance of stimulant abuse as a means of keeping pace with increasingly rapid technolo- gies for communication and business transactions.

Chapter 12 Performance-Enhancing Drugs and Drug testing in Sports ■ 311

standard for a sense of sexuality and social acceptance. This standard will not be news at all to women, but it is a fairly recent development in men. Anabolic steroids as a way of accelerating the effects of weight training are increasing in our culture. One high school senior has said, “The majority now are guys that don’t do it for sports. They do it for girls. For the look.” Another senior has remarked on a different kind of lifter in weight rooms and gyms: the vanity body builder. As he expressed it, “We notice a lot of kids now; they just want this certain type of body—with the abs and the ripped chest—and they want it quick.”38 An exercise

physiologist has remarked on the intense social pres- sures that are involved:

The teenage years are the skinniest and most awk- ward, and the idea of being the skinniest kid in the locker room is absolutely terrifying to a teenage boy.39

As usual, Internet web sites deliver mixed messages, promoting anabolic steroids as well as steroid precursors such as androstenedione with the promise “You’ll get huge!” while saying on the labels of their products that people younger than age eighteen should not take them or that they should consult a physician first.

Summary

drug-Taking Behavior in Sports ● The use of performance-enhancing (ergogenic)

drugs in athletic competition has a long history, dat- ing from the original Olympic Games in ancient Greece.

● In the modern era, the principal type of performance- enhancing drugs has been anabolic steroids. These synthetic drugs are all based on variations of the testos- terone molecule.

● Since the late 1980s, anabolic steroids have been pop- ular with body builders as well as competitive athletes. This latter group typically takes steroids in enormous quantities and administers them in a largely unsuper- vised fashion.

● Recently, great concerns have been raised about the use of anabolic steroids, as well as other performance- enhancing drugs, in major league baseball.

The hazards of Anabolic Steroids ● The hazards of steroid use include liver tumors, mood

swings, and increased aggressiveness. ● For men, the effects include lower sperm count,

enlargement of the breasts, atrophy of the testicles, baldness, and severe acne. For women, masculiniz- ing changes occur, only some of which are reversible when steroids are withdrawn.

patterns of Anabolic Steroid Abuse ● Since 1990, anabolic steroids have been classified

as Schedule III controlled substances, making their possession and sale without a specific medical pre- scription illegal. In 2004, steroid precursors were added to the category of Schedule III controlled sub- stances. These drugs are now distributed through il- licit black-market channels.

● About 13 to 18 percent of individuals taking large doses of steroids develop both physical and psycho- logical dependence.

Nonsteroid hormones and performance-Enhancing Supplements ● Human growth hormone (hGH) is a nonsteroid hor-

mone that has been used for performance-enhancing purposes.

● Two dietary supplements, androstenedione and cre- atine, have been prominent recently as performance- enhancing aids.

Nonmedical Use of Stimulant medication in Baseball ● Although amphetamines were officially banned in

major league baseball (MLB) in 2005, for a long time players had been taking amphetamines to stay focused and ward off fatigue.

● In 2007, an unusually large number of MLB players reported taking stimulant medications for ADHD treat- ment, raising suspicions that this was an effort to circum- vent prohibitions against nonmedical stimulant use.

current drug-Testing procedures and policies ● Drug-testing procedures, chiefly for those in organized

athletics, have become increasingly sophisticated in their ability to detect the presence of banned substances.

● Two major techniques, based either on urine or on oral-fluid (saliva) samples, are enzyme immunoassay (EIA) and a combination of gas chromatography and mass spectrometry (GC/MS).

● The ultimate goal of drug-testing procedures is to make it impossible to yield either a false-negative or false-positive result. A sensitive test yields few false negatives, and a specific test yields few false positives.

312 ■ Part Four Enhancers and Depressants

Key Terms

acromegaly, p. 304 adrenocortical steroids, p. 295 anabolic, p. 295 anabolic-androgenic

steroids, p. 295 anabolic steroids, p. 295

androgenic, p. 295 androstenedione, p. 305 creatine, p. 305 EMIT (enzyme multiplied

immunoassay technique), p. 308

enzyme immunoassay (EIA), p. 306

ergogenic, p. 294 gas chromatography/mass

spectrometry (GC/MS), p. 307

gynecomastia, p. 299 human growth hormone

(hGH), p. 304 muscle dysmorphia, p. 302 priapism, p. 299

Endnotes

1. Kepner, T. (2009, February 18). “We weren’t taking Tic Tacs.” As team looks on, Rodriguez details his use of ste- roids. New York Times, pp. B1, B15. Quotation on p. B1.

2. Kepner, T. (2010, January 12). McGwire admits steroid use in 1990s, his years of magic. New York Times, pp. B10, B14. Quotation on p. B10.

3. Dolan, E. F. (1986). Drugs in sports (rev. ed.). New York: F. Watts, pp. 17–18. Meer, J. (1987). Drugs and sports. New York: Chelsea House, pp. 2, 61–75. Quotation from Scott, J. (1971, October 17). It’s not how you play the game, but what pill you take. New York Times Maga- zine, pp. 40–41, 106–113. Taylor, W. N. (1991). Macho medicine: The history of the anabolic steroid epidemic. Jefferson, NC: McFarland and Co., pp. 3–16. Wadler, G. I., and Hainline, B. (1989). Drugs and the athlete. Philadelphia: F. A. Davis, pp. 3–17.

4. Bhasin, S.; Storer, T. W.; Berman, N.; Callegari, C.; Clevenger, B.; et al. (1996). The effects of supraphysi- ologic doses of testosterone on muscle size and strength in normal men. New England Journal of Medicine, 335, 1–7. Lombardo, J. (1993). The efficacy and mechanisms of action of anabolic steroids. In C. E. Yesalis (Ed.), Anabolic steroids in sport and exercise. Champaign, IL: Human Kinetics Publishers, p. 100.

5. Scott, J., It’s not how you play the game, p. 41. 6. Catlin, D. H., and Murray, T. H. (1996). Performance-

enhancing drugs, fair competition, and Olympic sport. Journal of the American Medical Association, 276, 231–237. Maimon, A. (2000, February 6). Doping’s sad toll: One athlete’s tale from East Germany. New York Times, pp. A1, A6. Yesalis, C. E.; Courson, S. P.; and Wright, J. (1993). History of anabolic steroid use in sport and exercise. In Yesalis, Anabolic steroids, pp. 1–33.

7. Litsky, F. (2003, March 6). International drug code is adopted. New York Times, p. D5. Longman, J. (2003, October 24). Steroid is reportedly found in top runner’s urine test. New York Times, p. D2. Macur, J. (2008, October 9). Beijing Games blood samples to be retested for new drug. New York Times, pp. B17, B20. Macur, J. (2012, October 11). Details of doping scheme paint Arm- strong as leader. New York Times, pp. A1, B15. Macur, J. (2013, January 5). In reversal, Armstrong is said to weigh admitting drug use. New York Times, kjpp. A1, D4. Starr,

M. (2003, November 3). Blowing the whistle on drugs: A raid on a California laboratory threatens to blemish America’s athletes—again. Newsweek, pp. 60–61. Vecsey, G. (2002, March 1). More curious material in skiing’s closet. New York Times, pp. D1, D4. World Anti-Doping Asso- ciation, Montreal.

8. W. W. F.’s McMahon indicted (1993, November 19). New York Times, p. B12. Yesalis, Courson, and Wright, History of anabolic steroid use, pp. 40–42.

9. Curry, J. (2005, November 16). Baseball backs stiffer penalties for steroid use. New York Times, pp. A1, D2. Kepner, T. (2009, July 31). A stain keeps spreading. New York Times, pp. B10, B11. Macur, J. (2011, April 14). Bonds guilty of obstruction, but not of perjury. New York Times, p. A1. B15. Macur, J. (2012, June 19). Clemens found not guilty of lying about drug use. New York Times, p. A1. Vecsey, G. (2008, January 16). Spring training and the syringe generation. New York Times, pp. D1, D3.

10. Council on Scientific Affairs (1990). Medical and non- medical uses of anabolic-androgenic steroids. Journal of the American Medical Association, 264, 2923–2927. Hartgens, F., and Kuipers, H. (2004). Effects of andro- genic-anabolic steroids in athletes. Sports Medicine, 34, 513–554. Perry, P. J.; Lund, B. C.; Deninger, M. J.; Kutscher, E. C.; and Schneider, J. (2005). Anabolic steroid use in weightlifters and bodybuilders: An Internet survey of drug utilization. Clinical Journal of Sport Medicine, 15, 326–330.

11. Neri, M.; Bello, S.; Bonsignore, A.; Cantatore, S.; Riezzo, I., et al. (2011). Anabolic androgenic steroids and liver toxicity. Mini Reviews in Medicinal Chemistry, 11, 430–437. Van Amsterdam, J.; Opperhuizen, A.; and Hartens, F. (2010). Adverse health effects of anabolic- androgenic steroids. Regulatory Toxicology and Pharma- cology, 57, 117–123.

12. DiPaolo, M.; Agozzino, M.; Toni, C.; Luciani, A. B; et al. (2005). Sudden anabolic steroid abuse–related death in athletes. International Journal of Cardiology, 114, 114–117. Karch, S. B. (2009). Pathology of drug abuse (4th ed.). Boca Raton, FL: CRC Press, pp. 617-623. Maravelias, C.; Dona, A.; Stefanidou, M.; and Spilio- poulou, C. (2005). Adverse effects of anabolic steroids in athletes: A constant threat. Toxicology Letters, 158,

Chapter 12 Performance-Enhancing Drugs and Drug testing in Sports ■ 313

167–175. Urhausen, A.; Albers, T.; and Kindermann, W. (2004). Are the cardiac effects of anabolic steroid abuse in strength athletes reversible? Heart, 90, 496–501.

13. Su, T-P.; Pagliaro, M.; Schmidt, P. J.; Pickar, D.; Wolkowitz, O.; et al. (1993). Neuropsychiatric effects of anabolic steroids in male normal volunteers. Journal of the American Medical Association, 269, 2760–2764.

14. Pope, H. G., Jr.; Kouri, E. M.; and Hudson, J. I. (2000). Effects of supraphysiologic doses of testosterone on mood and aggressiveness in normal men: A randomized con- trolled trial. Archives of General Psychiatry, 57, 133–140. Stocker, S. (2000). Study provides additional evidence that high steroid doses elicit psychiatric symptoms in some men. NIDA Notes, 15(4), pp. 8–9. Trenton, A. J., and Currier, G. W. (2005). Behavioural manifestations of anabolic steroid use. CNS Drugs, 19, 571–595.

15. Adler, J. (2004, December 20). Toxic strength. Newsweek, pp. 45–52. Bahrke, M. S. (1993). Psychological effects of endogenous testosterone and anabolic-androgenic ste- roids. In Yesalis, Anabolic steroids, pp. 161–192. Doff, W. (2005, March 10). After a young athlete’s suicide, steroids called the culprit. New York Times, pp. A1, D8. Estrada, M.; Varshney, A.; and Ehrlich, B. E. (2006). Elevated testoster- one induces apoptosis in neuronal cells. Journal of Biologi- cal Chemistry, 281, 25492–25501. Longman, J. (2003, November 26). An athlete’s dangerous experiment: Using steroids enhanced his physique, but he died trying to stop. New York Times, pp. D1, D4.

16. National Institute on Drug Abuse (2000, April). Anabolic steroids. Research report series. Bethesda, MD: National Institute on Drug Abuse. Collins, R. (2003, January 5). Federal and state steroid laws. Posted on the web site of C., McDonald, and Gann, P. C., Attorneys-at-law, Nas- sau County and New York, NY, www.steroidlaw.com.

17. DEA leads largest steroid bust in history (2005, De- cember 15). Drug Enforcement Administration, U.S. Department of Justice. Johnston, L. D.; O’Malley, P. M.; Bachman, (J. G.; and Schulenberg, J. E. (2012v). Monitoring the Future: National survey results on drug use, 1975–2011. Vol. I: Secondary school students 2011. Ann Arbor, MI: Institute for Social Research, The Uni- versity of Michigan, Table 2-1.

18. Pope, C. G.; Pope, H. G.; Menard, W.; Fay, C.; Oli- vardia, R.; et al. (2005). Clinical features of muscle dys- morphia among males with body dysmorphic disorder. Body Image, 2, 395-400. Wroblewska, Anna-M. (1997). Androgenic-anabolic steroids and body dysmorphia in young men. Journal of Psychosomatic Research, 42, 225–234.

19. Bahrke, M. S.; Yesalis, C. E.; and Brower, K. J. (1998). Anabolic-androgenic steroid abuse and performance- enhancing drugs among adolescents. Sport Psychiatry, 7, 821–838. Beel, A.; Maycock, B.; and McLean, N. (1998). Current perspectives on anabolic steroids. Drug and Alcohol Review, 17, 87–103. Kashkin, K. B., and Kleber, H. D. (1989). Hooked on hormones? An anabolic steroid

addiction hypothesis. Journal of the American Medical Association, 262, 3166–3169. Monaghan, L. F. (2000). Bodybuilding, drugs, and risk. New York: Routledge. Perry, Lund, Deninger, Kutscher, and Schneider, Ana- bolic steroid use. Schrof, J. M. (1992, June 1). Pumped up. U.S. News and World Report, pp. 55–63.

20. Goldberg, L.; Mackinnon, D. P.; Elliot, D. L.; Moe, E. L.; Clarke, G.; and Cheong, J. (2000). The Adoles- cents Training and Learning to Avoid Steroids program. Archives of Pediatrics and Adolescent Medicine, 154, 332–338. Information courtesy of the Oregon Health and Science University, Portland, 2008. Moe, E. L.; Gold- berg, L. D.; MacKinnon, D. P.; and Cheong, J. (1999). Reducing drug use and promoting healthy behaviors among athletes: The ATLAS program. Medical Science Sports Exercise, 31(5), S122.

21. Kepner, “We weren’t taking Tic Tacs.” Quotation from Alex Rodriguez on p. B15.

22. Interlandi, J. (2008, February 25). Myth meets science. Newsweek, p. 48. Juhn, M. S. (2003). Popular sports supplements and ergogenic aids. Sports Medicine, 33, 921–939. Liu, H.; Bravata, D. M.; Olkin, I.; Friedlander, A.; et al. (2008). Systematic review: The effects of growth hormone on athletic performance. Annals of Internal Medicine, 148, 747–748. Macur, J. (2008, June). Who has the horse tranquilizers? Play, p. 18. Macur, J. (2008, October 9). Olympic blood samples to be retested. New York Times, p. B17. Macur, J. (2010, February 28). No doping scandals at Games, but time will tell. New York Times, Sportspage 9.

23. Tuller, D. (2005, January 18). For sale: “muscles” in a bottle. New York Times, pp. F5, F10.

24. Androstenedione (2001). PDR for nutritional supple- ments (1st ed.). Montvale, NJ: Thomson HealthCare, pp. 26–28. Juhn, Popular sports supplements. Leder, B. Z.; Longcope, C.; Catlin, D. H.; Ahrens, B.; and Schoenfeld, J. S. (2000). Oral androstenedione administration and serum testosterone concentrations in young men. Journal of the American Medical Association, 283, 779–782.

25. Denham, B. E. (2006). The Anabolic Steroid Control Act of 2004: A study in the political economy of drug policy. Journal of Health and Social Policy, 22, 51–78. Kepner, T. (2010, January 12). McGwire admits steroid use. New York Times, pp. B10, B14. Mravic, M. (2000, February 21). Ban it, bud. Sports Illustrated, pp. 24, 26.

26. Buford, T. W.; Kreider, R. B.; Stout, J. R.; et al. (2007). International Society of Sports Nutrition position stand: Creatine supplementation and exercise. Journal of the International Society of Sports Nutrition, 4, 6. Creatine,. PDR for nutritional supplements, pp. 114–117. Free- man, M. (2003, October 21). Scientist fears athletes are using unsafe drugs: Discovery of an undetected steroid confirms suspicions. New York Times, p. D2. Gregory, A. J. M., and Fitch, R. W. (2007). Sports medicine: Performance-enhancing drugs. Pediatric Clinics of North America, 54, 797–806.

314 ■ Part Four Enhancers and Depressants

27. Schmidt, M. S. (2008, January 16). Baseball is chal- lenged on rise in stimulant use. New York Times, pp. A1, A16. Quotation on p. A16. Schmidt, M. S. (2009, January 10). Baseball officials give report on amphetamine use among players. New York Times, p. D5.

28. Hamilton, M. McNeil (2003, February 23). Beating drug screening builds cottage industry. Evaders change faster than testing technology. Houston Chronicle, p. 2.

29. Wadler and Hainline, Drugs and the athlete, pp. 201–202. 30. Hatton, C. K. (2007). Beyond sports-doping headlines:

The science of laboratory tests for performance-en- hancing drugs. Pediatric Clinics of North America, 54, 713–733. Meer, Drugs and sports, pp. 92–95.

31. Alternate specimen testing policies may be set soon (2005, September). Occupational Health and Safety, p. 26. Cone, Edward J.; Presley, L.; Lehrer, M.; Seiter, W.; Smith, M.; et al. (2002). Oral fluid testing for drugs of abuse: Positive prevalence rates by Intercept immu- noassay screening and GC-MS-MS confirmation and suggested cutoff concentrations. Journal of Analytical Toxicology, 26, 540–546.

32. Allen and Hanbury’s athletic drug reference (1994). Durham NC: Clean Data, pp. 65–66. Baden, L. R.; Horowitz, G.; Jacoby, H.; and Eliopoulos, G. M. (2001). Quinolones and false-positive urine screening for opiates by immunoassay technology. Journal of the American Medical Association, 286, 3115–3119. Struempler, R. E. (1987, May/June). Excretion of codeine and morphine following ingestion of poppy seeds. Journal of Analytical Toxicology, 11, 97–99. Wadler and Hainline, Drugs and the athlete, pp. 208–209.

33. Catlin, D.; Wright, J.; Pope, H.; and Liggett, M. (1993). Assessing the threat of anabolic steroids: Sportsmedicine update. The Physician and Sportsmedicine, 21, 37–44.

34. Rosenberg, R. (2000, October 12). Citgo to use Avitar drug tests, job applicants to undergo new saliva-based exam. Boston Globe, p. C3.

35. Brookman, R. R. (2008). Unintended consequences of drug and alcohol testing in student athletes. AAP (American Academy of Pediatrics) Grand Rounds, 19,

15–16. Editorial: To test or not to test: Screening for substance use in adolescents. Journal of Adolescent Health, 38, 329-331. Yamaguchi, R.; Johnston, L. D.; and O’Malley, P. M. (2003). Relationship between student illicit drug use and school drug-testing policies. Journal of School Health, 73, 159–164.

36. Quotation from C. E. Yesalis. In Wright, J. E, and Cowart, V. S. (1990). Anabolic steroids: Altered States. Traverse City, MI: Cooper Publishing, p. 196. Schwerin, M. J.; Corcoran, K. J.; Fisher, L.; Patterson, D.; Askew, W.; et al. (1996). Social physique anxiety, body esteem, and social anxiety in bodybuilders and self-reported anabolic steroid users. Addictive Behaviors, 21, 1–8.

37. Goldman, B., and Klatz, R. (1992). Death in the locker room II: Drugs and sports. Chicago: Elite Sports Medi- cine Publications, pp. 23–24. McHenry, C. R. (2007, December). Presidential address to the American Associ- ation of Endocrine Surgeons: The illicit use of hormones for enhancement of athletic performance: A major threat to the integrity of organized athletic competition. Sur- gery, 785–792. Shermer, M. (2008, April). The doping dilemma. Scientific American, pp. 82–89.

38. Egan, T. (2002, November 22). Body-conscious boys adopt athlete’s taste for steroids. New York Times, pp. A1, A24. Quotations on p. A24. Kolata, G.; Longman, J.; Weiner, T.; and Egan, T. (2002, December 2). With no answers on risks, steroid users still say “yes.” New York Times, pp. A1, A19. Pope, H. G., Jr., Phillips, K. A., and Olivardia, R. (2002). The Adonis complex: How to iden- tify, treat, and prevent body obsession in men and boys. New York: Simon and Schuster. Roosevelt, M. (2010, January 14). When the gym isn’t enough. New York Times, pp. E1, E8.

39. Kilgannon, C. (2001, May 27). Strong Island: More youngsters seek great physiques, and risky ways to get them. New York Times, Section 14 (Long Island), pp. 1, 9. Quotation on p. 9. Kolata, With no answers on risks, ste- roid users still say “yes,” pp. A1, A10. Morgan, R. (2002). The men in the mirror. Chronicle of Higher Education, 49, A53–A54.

315

“I remember,” Julio says, taking quick, nervous puffs from his

cigarette, “when I was a little kid, maybe eight or nine, and

I used to take the garbage out for my mother, I’d always

see tubes from airplane glue under the stairwell in our

apartment house and in the alley out back. At first, glue

just meant building models to me. But I’d see people sniff-

ing it, under the stairwell. I was curious, and one day I tried

it. It made me feel like I was in a trance. It wasn’t really

exciting, but I did it again and again until we moved, and

in the new neighborhood people weren’t into glue and

I didn’t see the empty tubes to remind me anymore.”1

— A teenager relating his early experience with inhalant abuse

After you have completed this chapter, you should have an understanding of

▶ The acute and chronic effects of barbiturates as sedative- hypnotic drugs

▶ The development of benzodiazepines as antianxiety medications

▶ Current sedative-hypnotics and antianxiety medications

▶ Present-day concerns about gamma-hydroxybutyrate (GHB)

▶ The history of psychoactive inhalants

▶ The acute effects and dangers of glue, solvent, or aerosol spray inhalation

▶ Patterns of inhalant abuse and its chronic effects

▶ Society’s response to concerns about inhalant abuse

C h a p t e r

1 3Depressants and Inhalants

316 ■ Part Four Enhancers and Depressants

Just as cocaine, amphetamines, and other stimulants bring us up, depressants bring us down. Just as people desire to be stronger, faster, and more attuned to the world, they also desire to move apart from that world, reduce the stress and anxiety of their lives, and fall asleep more easily. We examined in Chapter 5 the powerful effects of opioids not only to relieve pain but also to provide the means to retreat from the world around them. In Chapter 8, we examined the age-old allure of alcohol to relax our mind and body.

In the first part of this chapter, we will focus on a group of non-opioid, nonalcoholic depressant drugs called sedative-hypnotics, so named because they calm us down (from the Latin verb sedare, meaning “to calm or be quiet”) and produce sleep (from the Greek noun hypnos, meaning “sleep”). Several types of sedative- hypnotic drugs exist, ranging from drugs that were intro- duced more than two hundred years ago to others that have become available only recently.

A separate but related category consists of prescrip- tion drugs that provide specific relief from stress and anxiety without sedating us. These drugs have often been referred to as tranquilizers because of their abil- ity to make us feel peaceful or tranquil, but we will call them by their currently accepted name, antianxiety drugs. Unfortunately, sedative-hypnotics and antianxi- ety drugs have been subject not only to legitimate medi- cal use but to misuse and abuse as well. Many of them can be obtained through illicit sources as street drugs and are consumed for recreational purposes. The psy- chological problems and physical dangers associated with the misuse and abuse of these depressants are of particular concern.

This chapter also looks at a category of depressant drugs known as inhalants, a group of chemicals that emit breathable vapors and produce intoxicating effects. These chemicals do not need to be acquired in a phar- macy, a convenience store, a liquor store, or even on the street. They can be found under the sink, in kitchen or bathroom cabinets, in the basement, or in the garage.

Ordinary household products frequently have the poten- tial to intoxicate if they are sniffed or inhaled. When you consider that these substances are readily available to anyone in a family, including its youngest members, the consequences of their abuse become especially troubling. Glues, solvents, and other inhalant products will be exam- ined as dangerous recreational drugs in our society today.

Barbiturates

In 1864, the German chemist Adolf von Baeyer com- bined a waste product in urine called urea and an apple extract called malonic acid to form a new chemical compound called barbituric acid. There are two oft-told stories about how this compound got its name. One story has it that Von Baeyer had gone to a local tavern to celebrate his discovery and encountered a number of artillery officers celebrating the feast day of St. Barbara, the patron saint of explosives handlers. Von Baeyer was inspired by their celebration, and the name “barbituric acid” came to mind. The other story attributes the name to a relationship with a certain barmaid (perhaps at the same tavern) whose name was Barbara.2

Whichever story is true (if either is), Von Baeyer’s discovery of barbituric acid set the stage for the develop- ment of a class of drugs called barbiturates. Barbituric acid itself has no behavioral effects, but when additional molecular groups combine with the acid, depressant effects are observed. In 1903, the first true barbiturate,

sedative-hypnotics: A category of depressant drugs that provide a sense of calm and sleep.

antianxiety drugs: Medications that make the user feel more peaceful or tranquil; also called tranquilizers.

inhalants: Chemicals that produce breathable vapors. They produce euphoriant and depressant ef- fects when sniffed or inhaled.

barbiturate (bar-BIT-chur-rit): A drug within a family of depressants derived from barbituric acid and used as a sedative-hypnotic and antiepileptic medication.

by the numbers . . .

70 million Approximate number of Americans who suffer from insomnia

12 Percentage of eighth graders in 2011 who reported that they had used inhalants to get high at some previous time in their lives

1,000’s The estimated number of house- hold products containing toxic substances that can be ingested through inhalation

Sources: Johnston, L. D.; O’Malley, P. M.; Bachman, J. G.; and Schulenberg, J. E. (2012, December 19). The rise in teen marijuana use stalls, synthetic marijuana use levels, and use of “bath salts” is very low. University of Michigan News Service, Ann Arbor, MI, Table 1. Press release: U.S. sleep aids market grows to $23 billion, as Americans battle insomnia, sleep disorders (2008, June 6). Marketdata Enterprises, Tampa, FL.

Chapter 13 Depressants and Inhalants ■ 317

diethylbarbituric acid, was created and marketed under the name Veronal. Over the next thirty years, several major barbiturate drugs were introduced: phenobarbital (brand name: Luminal), amobarbital (brand name: Amytal), pentobarbital (brand name: Nembutal), and secobarbital (brand name: Seconal).

Categories of Barbiturates Barbiturates all share a number of common features. They are relatively tasteless and odorless, and at suffi- cient dosages, they reliably induce sleep, although the quality of sleep is a matter that will be discussed later. Because they slow down neural activity in the central nervous system (CNS), an important therapeutic appli- cation of barbiturates has been in the treatment of sei- zure disorders (epilepsy).

Barbiturates have elimination half-lives that range from 10 to 40 hours (in the case of amobarbital) to 50 to 120 hours (in the case of mephobarbital). All other factors being equal, injectable forms of barbiturates are shorter-acting than orally administered forms of the same drug because it takes longer for the drug to be absorbed when taken by mouth and longer for it to be eliminated from the body (Table 13.1). Naturally, a higher dose of any drug lasts longer than a lower dose because it takes longer for all of the drug to be eliminated from the body. Thiopental (brand name: Pentothal), a barbiturate used in surgical anesthesia, takes effect extremely rapidly (within seconds) and lasts only a few minutes unless administered in a continuous fashion. For this rea- son, it is referred to as an ultra-short-acting barbiturate.

Because this feature has little appeal to a person seeking a recreational drug, ultra-short-acting barbiturates are not commonly abused.

Acute Effects of Barbiturates You can visualize the effects of barbiturates on the body and the mind in terms of points along a scale ranging from mild relaxation on one end to coma and death on the other. In this sense, barbiturate effects are the same as the effects of depressants in general. The particular point that is achieved depends on the dose level that is taken.

At very low doses, the primary result of oral adminis- trations of a barbiturate is relaxation and, paradoxically, a sense of euphoria. These effects derive chiefly from a disinhibition of the cerebral cortex, in which nor- mal inhibitory influences from the cortex are reduced. These symptoms are similar to the inebriating or intoxi- cating effects that result from low to moderate doses of alcohol (Drugs . . . in Focus).

As the dose level increases, lower regions of the brain concerned with general arousal become affected.

phenobarbital (FEEN-oh-BAR-bih-tall): A long-acting barbiturate drug, usually marketed in generic form.

amobarbital (AY-moh-BAR-bih-tall): An intermedi- ate-acting barbiturate drug. Brand name is Amytal.

pentobarbital (PEN-toh-BAR-bih-tall): A short-acting barbiturate drug. Brand name is Nembutal.

secobarbital (SEC-oh-BAR-bih-tall): A short-acting barbiturate drug. Brand name is Seconal.

TABlE 13.1

Major barbiturates

GENERIC NAmE BRANd NAmE ElImINATIoN HAlF-lIFE IN HouRS RElATIvE PoTENTIAl FoR ABuSE

phenobarbital Luminal* 24–120 low

mephobarbital Mebaral 50–120 low

butalbarbital Pheniline Forte† 34–42 moderate

amobarbital Amytal 10–40 high

pentobarbital Nembutal 15–50 high

secobarbital Seconal 15–40 High

Note: Barbiturates take effect in a range of fifteen minutes to one hour, depending upon the type. Generally, the shorter-lasting barbiturates begin to act sooner.

*Phenobarbital is also available in combination with hyoscyamine, atropine, and scopolamine under the brand name Donnatal. †Several brands combine butalbarbital with acetaminophen.

Sources: Julien, R. M. (2005). A primer of drug action (10th ed.). New York: Worth, p. 146. Physicians’ desk reference (67th ed.) (2013). Montvale, NJ: PDR Network.

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At therapeutic doses (one 100-mg capsule of secobarbi- tal, for example), barbiturates make you feel sedated and drowsy. For this reason, patients are typically warned that barbiturates can impair the performance of driving a car or operating machinery. At higher doses, a hyp- notic (sleep-inducing) effect is achieved.

Historically, the primary use of barbiturates has been in the treatment of insomnia, and they were widely recommended for this purpose from 1903, when they were first introduced, until the develop- ment of safer alternatives in the 1960s. One of the reasons why barbiturates fell from favor was that the sleep induced by these drugs turned out to be far from normal. Barbiturates tend to suppress rapid eye move- ment (REM) sleep, which represents about 20 percent of everyone’s total sleep time each night. REM sleep is

associated with dreaming and general relaxation of the body. If barbiturates are consumed over many evenings and then stopped, the CNS will attempt to catch up for the lost REM sleep by producing longer REM peri- ods on subsequent nights. This REM-sleep rebound effect produces vivid and upsetting nightmares, along with a barbiturate hangover the next day, during which the user feels groggy and out of sorts. In other words, barbiturates may induce sleep, but a refreshing sleep it definitely is not.

The most serious acute risks of barbiturate use involve the possibility of a lethal overdose either from taking too high a dose level of the drug alone or from taking the drug in combination with alcohol, such as when a barbiturate is taken after an evening of drink- ing. In these instances, the sleeper can all too easily slip into coma and death, since an excessive dose produces an inhibition of the respiratory control centers in the brain. The mixture of barbiturates with alcohol pro- duces a synergistic effect (see Chapter 1) in which the combined result is greater than the sum of the effects of each drug alone.3

REm-sleep rebound: A phenomenon associated with the withdrawal of barbiturate drugs in which the quantity of rapid eye movement (REM) sleep increases, resulting in disturbed sleep and nightmares.

Drugs . . . in Focus

Is There Any Truth in “Truth Serum”? The idea that a sedative-hypnotic drug such as amobarbital (Amytal, or “sodium amytal”) may function as a “truth serum” is not at all new. It has been known for centuries that depressants can produce remarkable candor and free- dom from inhibition. The oldest example is simple alco- hol, whose effect on loosening the tongue led to the Latin proverb in vino veritas (“in wine, there is truth”).

Whether we are guaranteed truthfulness under any of these circumstances, however, is another matter entirely. Courts have ruled that expert opinion in criminal cases based solely on drug-assisted testimony cannot be admitted as evidence. Controlled laboratory studies have shown that individuals under the influence of Amytal, when pressed by questioners, are as likely to give convincing renditions of fabrications (outright lies) or fantasies as they are to tell the truth. So perhaps Amytal might be better described as a “say anything serum.”

Recently, the question of whether Amytal or other dep- ressant drugs should be used to gain information has arisen in connection with the interrogation of captured al Qaeda prisoners following the September 11, 2001, attacks. Legal

scholars have argued that the practice constitutes torture under international law. The United States has determined that such individuals are unlawful combatants, a designation that excludes them from protection under the Geneva Conven- tion guidelines prohibiting such practices for prisoners of war. On the record, U.S. officials deny that depressant drugs are being used to gain information from captives under American jurisdiction. It is possible that this practice is in effect in other countries to which captives have been transferred.

There is still no evidence that truthful information can be gained through the use of depressant drugs. Nonetheless, military and intelligence experts point to the potential for gaining some relevant information that might be “buried” in drug-induced ramblings.

Sources: CBS News (2003, April 23). Truth serum: A possible weapon. www.cbsnews.com. Keller, L. (2005). Is truth serum torture? American University International Law Review, 20, 523–612. Lillienfeld, S. O., and Landfield, K. (2008). Science and pseudoscience in law enforcement. Criminal Justice and Behavior, 35, 1215–1230. Michaelis, J. I. (1966). Quaere, whether “in vino veritas”: An analysis of the truth serum cases. Issues in Criminology, 2 (2), 245–267.

Chapter 13 Depressants and Inhalants ■ 319

Half of the lethal dose of secobarbital combined with one-fourth the lethal dose of alcohol can kill in a synergistic double whammy. In another typical case of accidental overdose, a person takes a sleep- ing pill and awakens drugged and confused a few minutes later, annoyed at being aroused. The person then forgetfully takes another pill, or several, from the nightstand, and goes to sleep forever. This is called “drug automatism,” a good reason not to keep medications within reach of the bed.4

During the period between 1973 and 1976, barbitu- rates were implicated in more than half of all drug-related deaths labeled as suicide by medical examiners. In fact, the potential of barbiturates for a lethal overdose is the major reason for their decline as a prescription sedative.5

Chronic Effects of Barbiturates The use of barbiturates as sleep medications often initi- ates a cycle of behavior that can lead to dependence. Even after brief use of barbiturates, anxiety may be temporarily increased during the day, and there may be an even greater degree of insomnia than before. In addition, because a barbiturate-induced sleep typically leaves a person feeling groggy the next morning, it is tempting to take a stimulant drug during the day to feel completely alert. At bedtime, the person still feels the stimulant effects and is inclined to continue taking a barbiturate to achieve any sleep at all. To make matters worse, the brain builds up a pharmacological tolerance to barbiturates quite quickly, requiring increasingly higher doses for an equivalent effect.

The withdrawal symptoms observed when bar- biturates are discontinued indicate a strong physical dependence on the drug. A person may experience a

combination of tremors (“the shakes”), nausea and vom- iting, intense perspiring, general confusion, convulsions, hallucinations, high fever, and increased heart rate. Not surprisingly, considering the parallels mentioned so far with alcohol, the barbiturate withdrawal syndrome closely resembles that of withdrawal after chronic alcohol abuse.

Professionals in the treatment of drug dependence often view the effects of barbiturate withdrawal as the most distressing, as well as the most dangerous, type of drug withdrawal. From a medical perspective, the with- drawal process is life-threatening unless it is carried out in gradual fashion in a hospital setting. Without medical supervision, abrupt withdrawal from barbiturates carries approximately a 5 percent chance of death.6

Current Medical Uses of Barbiturates Considering the problems of barbiturate use in the treatment of insomnia, it should not be surprising that the clinical use of barbiturates for this problem is essen- tially “obsolete.”7 Nonetheless, barbiturates continue to play an important role in the treatment of epileptic seizures. Phenobarbital and mephobarbital (two rela- tively long-acting barbiturates) are prescribed to prevent convulsions. Dose levels need to be adjusted and moni- tored carefully because the concentration must be high enough to control the development of seizures (despite the tendency for tolerance effects to occur over time) without being so high as to produce drowsiness. Other nonbarbiturate antiseizure medications commonly in use will be described in Chapter 15.

Patterns of Barbiturate Abuse There are clear indications that taking barbiturate drugs is positively reinforcing. Laboratory animals will eagerly press a lever to deliver intravenous injections of barbiturates, particularly the shorter-acting types, at rates that are equal to those for cocaine.8 When given the choice between pentobarbital and a nonbarbiturate depressant, and given no knowledge as to the identity of the drugs, human drug abusers reliably select an oral dose of pentobarbital.9

Barbiturate abuse reached its peak in the 1950s and 1960s. (Table 13.2). The principal reason for its decline after 1970 was that barbiturates became less widely available as prescription drugs. Stricter controls were placed on obtaining excessive amounts of barbiturates from pharmacies, whereas physicians, concerned with the potential of barbiturates for intentional suicide or unintentional lethal overdose, became reluctant to prescribe them on a routine basis.

Barbiturates and alcohol have frequently been combined in attempts to commit suicide.

320 ■ Part Four Enhancers and Depressants

Despite their decline as major drugs of abuse, however, barbiturates are still being abused. The 2011 University of Michigan survey of high school seniors found that 7 percent of them had used some form of barbiturates during their lifetime, down from 17 percent in 1975, and 4 percent had taken them within the past year, down from 11 percent in 1975.10

Nonbarbiturate Sedative-Hypnotics

As the hazards of barbiturate use became increasingly evident, the search was on for sedative-hypnotic drugs that were not derivatives of barbituric acid and had

fewer undesirable side effects. Unfortunately, these objectives were not realized.

One such drug, chloral hydrate, had been synthe- sized as early as 1832. As a depressant used for the treat- ment of insomnia, it has the advantage of not producing the REM-sleep rebound effect or bringing on the typical barbiturate hangover. A major disadvantage, however, is that it can severely irritate the stomach. Like other depressants, it is also highly reactive when combined with alcohol. In the nineteenth century, a few drops of chloral hydrate in a glass of whiskey became the infa- mous “Mickey Finn,” a concoction that left many an unsuspecting sailor unconscious and eventually “shang- haied” onto a boat for China. You might say that chlo- ral hydrate was an early precursor of the modern-day “date-rape” drug (see pages 326–327).

The development of methaqualone (brand names: Quaalude, Sopor), first introduced in the United States in 1965, was a further attempt to achieve the perfect sleeping pill. In 1972, methaqualone had become the sixth-best-selling drug for the treatment of insom- nia. During the early 1970s, recreational use of meth- aqualone (popularly known as “ludes” or “sopors”) was rapidly spreading across the country, aided by its unfounded reputation of having aphrodisiac proper- ties. In 1984, this drug’s legal status changed to that of a Schedule I controlled substance, the most restricted classification, which indicates a high potential for abuse and no medical benefits. Although it is no longer manu- factured by any pharmaceutical company, methaqua- lone is still available as an illicit drug and qualifies as a “date-rape” drug.11 It is either manufactured in domes- tic underground laboratories or smuggled into the coun- try from underground laboratories abroad.

The Development of Antianxiety Drugs

If social historians consider the 1950s “the age of anxi- ety,” then it is appropriate that this period also would be marked by the development of drugs specifically intended to combat that anxiety. These drugs were originally called minor tranquilizers, to distinguish them from other drugs regarded as major tranquilizers and developed at about the same time to relieve symptoms of schizophrenia. This terminology is no longer used today, for we now know that the pharmacological dif- ferences between the two drug categories are more than simply a matter of degree. Anxious people (and even people who are not bothered by anxiety) are not affected by drugs designed to treat schizophrenia. The current,

chloral hydrate: A depressant drug once used for the treatment of insomnia. It is highly reactive with alcohol and can severely irritate the stomach.

methaqualone (mEH-tha-QuAY-lone): A nonbarbitu- rate depressant drug once used as a sedative. Brand name is Quaalude.

TABlE 13.2

Street names for various barbiturates

TYPE oF BARBITuRATE

STREET NAmE

pentobarbital (Nembutal)

blockbusters, nebbies, nembies, nemmies, yellow bullets, yellow dolls, yellow jackets, yellows

amobarbital (Amytal)

blue angels, bluebirds, blue bullets, blue devils, blue dolls, blue heavens, blues

secobarbital (Seconal)

F-40s, Mexican reds, R.D.s, redbirds, red bullets, red devils, red dolls, reds, seccies, seggies,

secobarbital and amobarbital (Tuinal)

Christmas trees, reds & blues, trees, tuies

barbiturates in general

barbs, downers, down, goofballs, G.B.s, goofers, idiot pills,

Note: Like any other street drug, illicit barbiturate capsules often contain an unknown array of other substances, includ- ing strychnine, arsenic, laxatives, and milk sugars. Any yellow capsule is likely to be “marketed” as Nembutal, any blue capsule as Amytal, and any red capsule as Seconal.

Source: Drug Enforcement Administration (2011). Drugs of abuse: A drug resource guide. Washington, DC: Drug Enforcement Administration, U.S. Department of Justice, p. 79. Henningfield, J. E., and Ator, N. A. (1986). Barbiturates: Sleeping potion or intoxicant? New York: Chelsea House, p. 82.

Chapter 13 Depressants and Inhalants ■ 321

and more logical, practice is to refer to drugs in terms of a specific action and purpose. The minor tranquilizers are now called antianxiety drugs or anxiolytic (“anxiety- reducing”) medications.

The first antianxiety drug to be developed was meprobamate (brand name: Miltown), named in 1955 for a New Jersey community near the pharmaceutical company that first introduced it. Miltown became an immediate hit among prescription drugs, making its name a household word and essentially a synonym for tranquil- izers in general. It was the first psychoactive drug in history to be marketed specifically as an antianxiety medication.12

Meprobamate had advantages and disadvantages. On the positive side, the toxic dose was relatively high, so the possibility of suicide was more remote than with alcohol, barbiturates, and other depressants. In addition, judging from the reduction in autonomic responses to stressors, there were genuine signs that people on this medication were actually less anxious. On the negative side, motor reflexes were diminished, making driving more hazardous. People often complained of drowsi- ness, even at dose levels that should have only been calming them down. Meprobamate also produced both physical and psychological dependence, at slightly more than twice the normal recommended daily dose.13 This was not a very wide margin for possible abuse, and as a result, meprobamate was classified as a Schedule IV controlled substance, requiring limits on the number of prescription refills. By 1960, meprobamate had been eclipsed by a newer and quite different class of antianxi- ety drugs called benzodiazepines.

Benzodiazepines

The introduction of a group of drugs called benzo- diazepines was a dramatic departure from all earlier attempts to treat anxiety. On the one hand, for the first time, there now were drugs that had a selective effect on anxiety itself, instead of producing a generalized reduc- tion in the body’s overall level of functioning. It was their “tranquilizing” effects, rather than their sedative effects, that made benzodiazepines so appealing to mental health professionals. On the other hand, it is important to distinguish between the well-publicized virtues of benzodiazepines when they were introduced in the 1960s and the data that accumulated during the 1970s as millions of people experienced these new drugs. Although they are certainly very useful in the treatment of anxiety and other stress-related problems, long-acting benzodiazepines are no longer recognized as the miracle drugs they were promoted to be when they first entered the market.

Medical Uses of Benzodiazepines The first marketed benzodiazepine, chlordiazepoxide (brand name: Librium), was introduced in 1960, fol- lowed by diazepam (brand name: Valium) in 1963. Table 13.3 lists the major benzodiazepine drugs cur- rently on the market. They are all chemically related, but their potencies and time courses vary considerably. Valium, for example, is five to ten times stronger than

meprobamate (mEH-pro-BAYm-ate): A nonbarbi- turate antianxiety drug and sedative. Brand name is Miltown.

benzodiazepines (BEN-zoh-dye-AZ-eh-pins): A family of antianxiety drugs. Examples include diazepam (Valium), chlordiazepoxide (Librium), and triazolam (Halcion).

chlordiazepoxide (CHloR-dye-az-eh-PoX-ide): A major benzodiazepine drug for the treatment of anxiety. Brand name is Librium.

diazepam (dye-AZ-eh-pam): A major benzodiazepine drug for the treatment of anxiety. Brand name is Valium.

TABlE 13.3

The leading benzodiazepines on the market

TRAdE NAmE

GENERIC NAmE

ElImINATIoN HAlF-lIFE

(IN HouRS)

long-acting benzodiazepines

Valium Diazepam 20–50

Librium Chlordiazepoxide 8–24

Limbitrol chlordiazepoxide and amitriptyline (an antidepressant)

8–24

Dalmane Flurazepam 70–160

Tranxene Clorazepate 50–100

Intermediate-acting benzodiazepines

Ativan Lorazepam 10–24

Klonopin Clonazepam 18–50

ProSom estazolam 13–35

Short-acting benzodiazepines

Restoril

Versed

temazepam

midazolam

8–35

1.5–4.5

Halcion triazolam 1.5–5

Xanax alprazolam 11–18

Note: Klonopin is available in orally disintegrating wafers for panic-attack patients who need the medication in an easily administered form.

Sources: Julien, R.M. (2005). A primer of drug action (10th ed.). New York: Worth, p. 169. Physicians’ desk reference (67th ed.) (2013). Montvale, NJ: PDR Network.

322 ■ Part Four Enhancers and Depressants

Librium and takes effect about an hour sooner. The relatively quicker response from Valium is a principal factor in making it more popular than Librium.

The variations in the benzodiazepines’ effects have led to different recommendations for their medical use. Oral administration of the relatively long-acting ben- zodiazepines, in general, is recommended for relief from anxiety, with the effects beginning thirty min- utes to four hours after ingestion. Besides Librium and Valium, other examples of this type include fluraz- epam (brand name: Dalmane) and clorazepate (brand name: Tranxene). When a very quick effect is desired, an injectable form of diazepam is used—for example, to reduce the symptoms of agitation that follow alcohol withdrawal (delirium tremens, or the DTs), as an anti- convulsant for epileptic patients, or as a pre-anesthetic drug to relax the patient just prior to surgery. Shorter- acting oral benzodiazepines are recommended for sleeping problems because their effects begin more quickly and wear off well before morning. Examples of this type include alprazolam (brand name: Xanax) and temazepam (brand name: Restoril).

Interestingly, benzodiazepines work best when the physician prescribing the medication is perceived as being warm, has a positive attitude toward use of antianxiety drugs, and believes that the patient will improve.14 The positive impact of such psychological factors on the outcome of treatment underscores the importance of the physician–patient relationship, along with the genuine pharmacological effects of the drugs themselves.

Acute Effects of Benzodiazepines In general, benzodiazepines are absorbed relatively slowly into the bloodstream, so their relaxant effects develop more gradually and last longer than those of bar- biturates. This is because benzodiazepines are absorbed from the small intestine rather than the stomach, as is the case with barbiturates. The relatively greater water solubility and, by implication, the relatively lower fat solubility of benzodiazepines also are factors.

The major advantage that benzodiazepines have over barbiturates and other drugs previously used to control anxiety is their higher level of safety. Respiratory centers in the brain are not affected by benzodiazepines, so it is rare for a person to die of respiratory failure from an accidental or intentional overdose. Even after taking fifty or sixty times the therapeutic dose, the person will still not stop breathing. It is almost always possible to arouse a person from the stupor that such a drug quan- tity would produce. In contrast, doses of barbiturates or

nonbarbiturate sedatives that are ten to twenty times the therapeutic dose are lethal. Yet we must remember that this higher level of safety assumes that no alcohol or other depressant drugs are being taken at the same time.15

Despite the relative safety of benzodiazepines, this drug family poses a number of medical risks for spe- cial populations. For elderly patients, for example, the rate of elimination of these drugs is slowed down sig- nificantly, resulting in the risk of a dangerously high buildup of benzodiazepines after several doses. In the case of a long-acting benzodiazepine such as Valium or Librium, the elimination half-life is as long as ten days. An elderly patient with this rate of elimination would not be essentially drug-free until two months had passed since she or he took the drug.

The continued accumulation of benzodiazepines in the elderly can produce a form of drug-induced demen- tia in which the patient suffers from confusion and loss of memory. Without understanding the patient’s medi- cation history, one could easily mistake these symp- toms for the onset of Alzheimer’s disease. An additional problem with benzodiazepines is the increased risk of falls and bone fractures. It is for these reasons that long- acting benzodiazepines are no longer recommended for this age group, and those who are currently taking these drugs are being encouraged to switch to shorter-acting forms or alternative non-pharmacological treatments.16

Chronic Effects of Benzodiazepines The benzodiazepines were viewed originally as having few, if any, problems related to a tolerance effect or an acquired dependence. We now know that the anxiety- relieving aspects of benzodiazepines show little or no tolerance effects when the drugs are taken at prescribed dosages, but there is a tolerance to the sedative effects. In other words, when the drugs are taken for the pur- pose of relieving anxiety, there is no problem with toler- ance, but when they are taken for insomnia, more of the drug may be required in later administrations to induce sleep.17

We also now know that physiological symptoms appear when benzodiazepines are withdrawn, an indi- cation of benzodiazepine dependence. In the case of long-acting benzodiazepines, the slow rate of elimina- tion delays the appearance of withdrawal symptoms until between the third day and the sixth day follow- ing drug withdrawal. The first signs include an anxiety level that may be worse than the level for which the drug was originally prescribed. Later, there are symp- toms of insomnia, restlessness, and agitation. In general,

Chapter 13 Depressants and Inhalants ■ 323

however, withdrawal symptoms are less severe than those observed after barbiturate withdrawal, occur only after long-term use, and are gone in one to four weeks.18

How Benzodiazepines Work in the Brain The key factor in the action of benzodiazepines is the neurotransmitter gamma-aminobutyric acid (GABA), which normally exerts an inhibitory effect on the ner- vous system (see Chapter 3). When benzodiazepines are in the vicinity of GABA receptors, the actions of GABA are increased. The antianxiety drugs attach themselves to their own receptors on the membrane of neurons and, in doing so, heighten the effect of GABA. The facilitation of GABA produces a greater inhibition and a decreased activity level in the neurons involved.19

The receptor described in Figure 13.1 is a large protein molecule that has multiple binding locations, arranged like docking sites for different kinds of boats. The receptor consists of three binding sites: one for sedative-hypnotics (including the barbiturates), one for benzodiazepines (and alcohol), and one for GABA. When GABA attaches to its binding site, there is greater inhibition if the benzodiazepine sites are also occupied at the time by a benzodiazepine drug than if they are not so occupied.20 The successful binding of a chemical at one site facilitates the binding at the others.

It is not difficult to imagine how cross-tolerance among various depressant drugs would occur. If two depressant drugs were to bind to the same receptor, the receptor would not be able to “tell the difference” between them. As far as the receptor is concerned, the effect would be the same. Evidently, sedative-hypnotics and benzodiazepines share this ability to lock into a common receptor with multiple binding locations.21

Patterns of Benzodiazepine Misuse and Abuse Benzodiazepines do not present the same potential for abuse that cocaine, alcohol, or the barbiturates do, for two primary reasons. First, benzodiazepines are only weak reinforcers of behavior. When trained to press a lever for an injection of Valium, for example, laboratory animals self-administer the drug, but at far less robust levels than they would self-administer pentobarbital or methaqualone. Studies with normal college student vol- unteers show that when subjects are given the choice between a placebo and Valium, and the true identity of neither choice is known, they actually prefer the pla- cebo. For these individuals, who presumably are not drug abusers and are relatively anxiety-free, the results show no indication of a positive Valium reaction.22 Second, the slow onset of a benzodiazepine effect pre- vents the sudden “rush” feeling that is characteristic of many abused drugs such as cocaine, heroin, and amphetamines.

This is not to say, however, that benzodiazepines fail to be abused. It is simply that their abuse exists largely in the context of abusing other drugs as well. Alcoholics, for example, may take benzodiazepines to reduce anxiety and other withdrawal symptoms in the context of their alcoholism. Heroin abusers may take benzodiazepines to augment their euphoria and reduce their anxiety when the opioid levels in their blood begin to fall.23

Historically speaking, the principal concern regard- ing benzodiazepines concerned the enormous quan- tity of prescriptions that were being written. In 1972, Valium ranked first (and Librium third) among the most frequently prescribed drugs of any type. At the height of their popularity in 1975, more than 100 million prescriptions for benzodiazepines were processed around the world, 85 million of them in the United States. It was estimated at the time that in Western Europe and North America, 10 to 20 percent of adults were taking benzo- diazepines on a fairly regular basis.24

Benzodiazepines have declined substantially in psy- chiatric practice as newer approaches to anxiety disor- ders have been pursued. Nonetheless, benzodiazepines remain widely prescribed drugs throughout the world, particularly for people over the age of sixty-five years, to treat problems of insomnia and anxiety. Although they are useful for short-term applications, adverse side effects can arise when benzodiazepines are taken over a long period of time. The potential for cognitive impair- ment among elderly people and the adverse effects when benzodiazepines are combined with alcohol were

Benzodiazepine receptor

GABA receptor

Sedative- hypnotic receptor

F I G u R E 1 3 . 1

A simplified view of the benzodiazepine receptor.

324 ■ Part Four Enhancers and Depressants

discussed earlier in this chapter. These possibilities have been a particular problem in European countries where wine is consumed on a regular basis.25

In recent years, considerable publicity has focused on the social and personal concerns surrounding the abuse of a specific benzodiazepine, flunitrazepam (brand name: Rohypnol). This drug is not legally avail- able in the United States but is accessible as a “club drug” through illicit channels (Health Alert).

Nonbenzodiazepine Depressants

Just as benzodiazepines represented a great advance over barbiturates, the development of new nonbenzo- diazepine drugs has provided better opportunities to treat sleep disorders and anxiety. Prominent examples of this new generation of medications are zolpidem,

H E A l T H A l E R T !

The dangers of Rohypnol as a date-Rape drug Flunitrazepam (brand name: Rohypnol) is a long-acting benzodiazepine not unlike diazepam (Valium), except that it is approximately ten times stronger. Because of its extreme potency and the fact that it is highly synergistic with alcohol, Rohypnol is not legally available in the United States. It is, however, approved for medical use in Europe and South America, where it is marketed by Hoffmann–La Roche Pharmaceuticals as a treatment for sleep disorders and as a surgical anesthetic. The U.S. supply of Rohypnol is smuggled into the country from Mexico and South America and sold for recreational use, frequently in its original bubble packaging.

The abuse potential of Rohypnol surfaced in the mid-1990s, when the number of pills seized by the U.S. Customs Service increased by 400 percent from 1994 to 1995 alone. Increased efforts by U.S. Customs and the Drug Enforcement Administration (DEA) have drasti- cally reduced the availability of Rohypnol in the United States, although the drug remains a matter of great concern.

Under such street names as “roofies,” “rope,” “wolfies,” “roches,” “R2,” and “Mexican Valium,” this drug has been promoted as an alcohol enhancer and as a strategy for getting drunk without having a blood-alcohol concentration level that would be defined as legal intoxi- cation. Rohypnol also has been involved in numerous date-rape cases in which victims had been unknowingly slipped the drug, causing them to pass out. The disinhibi- tion of behavior and the subsequent loss of all memory of the experience are similar to an alcohol-induced blackout (see Chapter 8).

At one time, Rohypnol was odorless, colorless, and tasteless, so it could be easily combined with an alcoholic beverage without detection. Recently, in response to in- stances of abuse, Hoffmann–La Roche has taken steps to reformulate the drug so that it turns blue when dissolved in a clear liquid. This helps to make Rohypnol somewhat

more noticeable to an unsuspecting drinker, but it is difficult to notice changes in beverage color under the dim illumination of a typical bar. Besides, in blue tropical drinks and punches, blue dye produces no color change at all.

Since 1996, U.S. federal law has provided for a twenty-year sentence for the use of Rohypnol in con- nection with rape or other violent crime. Unfortunately, Rohypnol is an increasingly accessible illicit drug. According to one law-enforcement official in Miami, “It may be easier for teenagers to obtain flunitrazepam (Rohypnol) than alcohol.” A recent study has found that a variety of benzodiazepines, all marketed by Hoffmann–La Roche, are being abused and linked to sexual assaults. Because these drugs all bear the same Roche imprint on the tablets, they are collectively known as “roches.”

Rohypnol is an example of a group of present-day “club drugs” that have a dangerous potential for abuse as date-rape drugs. Other examples include MDMA, or Ecstasy (see Chapter 6), and GHB (discussed later in this chapter).

Where to go for assistance: http://www.4woman.gov/faq/rohypnol.htm

This web site is sponsored by the National Woman’s Health Information Center, a service of the U.S. Department of Health and Human Services dedicated to women’s health issues.

Sources: Community Epidemiology Work Group (1996). Epidemiologic trends in drug abuse, Volume 1: High- lights and executive summary. Rockville, MD: National Institute on Drug Abuse, pp. 8, 64. Quotation on p. 64. Drug Enforcement Administration, U.S. Department of Justice, Washington, DC, 1997. Office of National Drug Control Policy (2003, February). ONDCP Drug Policy Clearing- house fact sheet: Rohypnol. Washington, DC: Executive Office of the President.

Chapter 13 Depressants and Inhalants ■ 325

eszopiclone, buspirone, beta blockers, and, strangely enough, antidepressants.

Zolpidem and Eszopiclone Zolpidem (brand name: Ambien) is not a benzodiaz- epine drug, but it binds to a specific subtype of GABA receptor. This is probably why it produces only some of the effects usually associated with benzodiazepines and is especially useful in the short-term treatment of insomnia. Its strong but transient sedative effects (with a half-life of about two hours) have led to the marketing of zolpidem, since its introduction in 1993, as a sedative- hypnotic rather than an antianxiety agent. Little or no muscle relaxation is experienced.

Introduced in 2004, eszopiclone (brand name: Lunesta, formerly known as Estorra) is also a non- benzodiazepine drug prescribed for the treatment of insomnia. As a result of successful clinical trials last- ing six months, the FDA has approved Lunesta for an interval of treatment that is longer than the recom- mended treatment with Ambien. Because its half-life of six hours is longer than that of Ambien, Lunesta has been helpful for people who have difficulty stay- ing asleep during the night as well as difficulty falling asleep.26

Buspirone Buspirone (brand name: BuSpar), has a number of remarkable features. It has been found to be equivalent to Valium in its ability to relieve anxiety, but, unlike the benzodiazepines in general, buspirone shows no cross- tolerance effects when combined with alcohol or other depressants and no withdrawal symptoms when discon- tinued after chronic use. When compared with benzo- diazepines, side effects are observed less frequently and are less troublesome to the patient; approximately 9 per- cent report dizziness, and 7 percent report headaches. Animals do not self-administer buspirone in laboratory studies, and human volunteers indicate an absence of euphoria.

Buspirone also fails to cause the impairments in motor skills that are characteristic of benzodiazepines. In other words, the relief of anxiety is attainable with- out the accompanying feelings and behavioral conse- quences of sedation. Perhaps anxiety and sedation do not have to be intertwined after all. Unlike benzodiaz- epines, buspirone does not affect GABA receptors in the brain but rather acts on a special subclass of serotonin receptors. Evidently, the influence of buspirone on sero- tonin produces the antianxiety effects.

Despite its virtues, however, buspirone has a dis- tinct disadvantage: a very long delay before anxiety relief is felt. It may take weeks for the drug to become com- pletely effective. This feature makes buspirone clearly inappropriate for relieving acute anxiety conditions, but patients suffering from long-term generalized anxiety disorder find it helpful as a therapeutic drug. An extra benefit of the delay in the action of buspirone is that it becomes highly undesirable as a drug of abuse. Do not expect to see news headlines in the future warning of an epidemic of buspirone abuse.27

Beta Blockers The traditional medical uses of beta-adrenergic-blocking drugs, commonly known as beta blockers, include slow- ing the heart rate, relaxing pressure on the walls of blood vessels, and decreasing the force of heart contractions. The combination of a beta-blocker drug and a diuretic is a frequent treatment for the control of high blood pressure. These drugs are also prescribed for individuals facing an anxiety-producing event, such as performing on the stage or giving a speech. Examples of beta blockers include atenolol (brand name: Tenormin), metoprolol (brand name: Lopressor), and propranolol (brand name: Inderal).

Antidepressants Another approach in the treatment of panic disorder, post-traumatic stress disorder, and social anxiety disor- der has been the use of antidepressant medications— specifically, selective serotonin reuptake inhibitors (SSRIs) such as sertraline (brand name: Zoloft) and par- oxetine (brand names: Paxil, Asima).28

zolpidem (Zol-pih-dem): A nonbenzodiazepine sedative-hypnotic drug, first introduced in 1993, for the treatment of insomnia. Brand name is Ambien.

eszopiclone (es-ZoP-eh-clone): A nonbenzodiaze- pine sedative-hypnotic, first introduced in 2005, for the treatment of insomnia. Brand name is Lunesta.

buspirone (BYoo-spir-rone): A nonbenzodiazepine antianxiety drug first introduced in 1986. Brand name is BuSpar.

beta blockers: Medicinal drugs that are traditionally used to treat cardiac and blood pressure disorders. They are also prescribed for individuals who suffer from “stage fright” or anxiety regarding a specific event. Examples include atenolol (brand name: Tenormin), metoprolol (brand name: Lopressor), and propanolol (brand name: Inderal).

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A Special Alert: The Risks of GHB

Of all the much-publicized club drugs to emerge in recent years, perhaps the most notorious is the CNS depressant gamma-hydroxybutyrate (GHB). First synthesized in the 1960s, GHB is produced natu- rally in the body in very small amounts, but no one has discovered its function. At one time, GHB was sold in health-food stores and similar establishments. It was considered to have steroid-enhancing and growth-hormone-stimulating effects, leading to interest among body builders (see Chapter 12). Other promo- tions focused on GHB as a sedative. By 1990, how- ever, numerous reports of GHB-related seizures and comas led the Food and Drug Administration (FDA) to

remove GHB from the legitimate market. Since then, the drug has gone underground. The manufacture of GHB is currently controlled by small clandestine labo- ratories, guided in many instances by formulas available on the Internet, and its sale is maintained by networks of illicit drug distributors.

Acute Effects Present-day GHB abuse focuses on its ability to pro- duce euphoria, an “out-of-body” high, in conjunction with a lowering of inhibitions. Frequently, a combina- tion of GHB and alcohol can lead to unconsciousness in about fifteen minutes and to subsequent amnesia about the experience. The notoriety of GHB as a date- rape drug stems from its being colorless, odorless, and virtually tasteless. As a result, it can be slipped easily into alcoholic beverages without the knowledge of the drinker.29

Protective Strategies for Women The vulnerability of women to being drugged with GHB while consuming alcohol in a club or bar is con- siderable (Portrait), but a number of protective strategies can be employed to minimize the risk.

■ Watch the person who pours you a drink, even if he or she is a friend or a bartender. Even better, do not drink what you cannot open or pour yourself. Avoid punch bowls and shared containers. Never accept a drink offered to you by a stranger.

■ Do not leave a drink alone—not while you are danc- ing, using the restroom, or making a telephone call. If you have left it alone, toss it out.

gamma-hydroxybutyrate (GHB) (GAm-ma heye-dRoX-ee-BYoo-tih-rate): A powerful depres- sant, often abused to induce euphoria and sedation. When slipped into an alcoholic beverage without the knowledge of the drinker, GHB has been employed as a date-rape drug.

Quick Concept Check 13.1

Understanding the Abuse Potential in Drugs Each of the following statements describes a particular attribute of a new drug. Based on material in this chapter, indicate whether each description, when taken by itself, increases or decreases the abuse potential of the drug.

1. Drug fails to produce euphoria at any dose levels.

2. Drug acts very quickly.

3. Drug is cross-tolerant to barbiturates and alcohol.

4. Drug is not available to the public.

5. There are tolerance effects when taking this drug.

6. The drug can be used without the need for medical supervision of dose or dosage schedule.

Answers: 1. decreases 2. increases 3. increases 4. decreases 5. increases 6. increases

This commercially available bar coaster is used to test for the presence of GHB in an alcoholic beverage.

Chapter 13 Depressants and Inhalants ■ 327

■ Appoint a designated “sober” friend to check up on you at parties, bars, clubs, and other social gatherings.

■ If a friend seems extremely drunk or sick after a drink and has trouble breathing, call 911 immediately.

■ If you have been slipped GHB, the drug will take effect within ten to thirty minutes. Initially, you will feel dizzy or nauseated or will develop a severe headache. You can be incapacitated rapidly. This is the time when having a nondrinking friend nearby is crucial.

■ If you wake up in a strange place and believe that you have been sexually assaulted while under the influ- ence of GHB, do not urinate until you have been admitted to a hospital. There is an approximately twelve-hour window of opportunity to detect GHB through urinalysis.

A test strip created by Drink Safe Technology is now available that can detect not only GHB but also Rohypnol and ketamine. A straw can be used to place a few drops of one’s drink on the test strip. If the liquid turns blue, there is a positive result. Unfortunately, when the drink contains dairy prod- ucts, an accurate detection cannot be made. Bar coasters have been developed that incorporate this

particular test strip. Never forget, however, that the original and all-time leading date-rape drug is alco- hol itself.30

Inhalants through History

The mind-altering effects of substances inhaled into the lungs have been known since the beginnings of recorded history. Burnt spices and aromatic gums were used in worship ceremonies in many parts of the ancient world; exotic perfumes were inhaled dur- ing Egyptian worship as well as in Babylonian ritu- als. Inhalation effects also figured prominently in the famous rites of the oracle at Delphi in ancient Greece, where trances induced by the inhaling of vapors led to mysterious utterances that were interpreted as prophe- cies. We know now, from archeological studies, that limestone faults underneath the temple at Delphi once caused petrochemical fumes to rise to the sur- face. The oracle was probably inhaling ethylene, a sweet-smelling gas that produces an out-of-body sense of euphoria.31

It was not until the latter part of the eighteenth cen- tury that reports about the inhalation of specific drugs began to appear. The two most prominent examples

P o r t r a i t Patricia White, GHB, and the “Perfect” Crime

Patricia White, a forty-seven- year-old mother of three, was at a party celebrating the birthday of her boss, Lorenzo Feal. According to testimony later given by White, as she was about to leave the party, Feal handed her a bottle of water. She took a gulp. A few hours later, White woke up in Feal’s bed, naked and nauseated. She had been drugged and raped. Doctors at the emergency department of the local hospital found traces of GHB in her system, and Feal was eventually convicted of using an anesthetic substance in per- petrating White’s rape.

A prosecuting attorney has called GHB “ideal for predators and tough for prosecutors” because it is so easily concealed in a drink. Without

toxicological evidence, it is difficult to prove that the rape

victim had not given consent to sex. Perhaps GHB should really be called an “acquaintance-rape and date-rape drug.”

In 1994, when GHB was relatively new, only 56 GHB-related emergency department “mentions” were reported through the DAWN system (see Chapter 1). By 2002, that number had grown to 3,300 before holding steady at about 1500–2400 between 2004 and 2011. Colleges and universi- ties, as well as commercial bars, have become justifiably alarmed. The Drug Enforcement Administration (DEA) has collaborated with the Rape, Abuse, and Incest National Network (RAINN) in an effort to promote a heightened

awareness of GHB and other “preda- tory” drugs such as Rohypnol.

Patricia White now counsels GHB rape victims and speaks out publicly about her personal story. In the case of GHB, the more you know about this drug, the safer you are.

Sources: Smalley, S. (2003, February 3). “The perfect crime”: GHB is color- less, odorless, leaves the body within hours—and is fueling a growing num- ber of rapes. Newsweek, p. 52. Substance Abuse and Mental Health Services Administration (2013). Drug Abuse Warning Network: National estimates of drug-related emergency visits, 2004– 2011. Rockville, MD: Substance Abuse and Mental Health Services Administra- tion, Excel files.

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were cases involving nitrous oxide and ether. These anesthetic drugs were first used as surgical analgesics in the 1840s, but they had been synthesized decades earlier. From the very start, word had spread of recre- ational possibilities.

Nitrous Oxide In 1798, at the precocious age of nineteen, the British chemist Sir Humphry Davy began formal investiga- tions of a newly synthesized gas called nitrous oxide. He immediately observed the pleasant effects of this “laughing gas” and proceeded to give nitrous oxide parties for his literary and artistic friends. By the early 1800s, recreational use of nitrous oxide became wide- spread both in England and in the United States as a nonalcoholic avenue to drunkenness. In the 1840s, public demonstrations were held in cities and towns, as a traveling show, by entrepreneurs eager to market the drug commercially.

It was at such an exhibition in Hartford, Connecticut, that a young dentist, Horace Wells, got the idea of using nitrous oxide as an anesthetic. One of the intoxicated participants in the demonstration had stumbled and fallen, receiving in the process a severe wound to the leg. Seeing that the man showed no evidence of being in pain, Wells was sufficiently impressed to try out the anesthetic possibilities himself. The next day, he under- went a tooth extraction while under the influence of nitrous oxide. He felt no pain during the procedure, and nitrous oxide has been a part of dental practice ever since, although controversy exists about its routine use as an anesthetic.32

During the 1960s, nitrous oxide inhalation reap- peared as a recreational drug. Tanks of compressed nitrous oxide were diverted for illicit use, and health professionals, like their counterparts one hundred years earlier, were reportedly hosting nitrous oxide parties. Small cartridges of nitrous oxide called whippets (gen- erally used by restaurants to dispense whipped cream) became available through college campus “head shops” and mail-order catalogs. The customary pat- tern of nitrous oxide abuse was to fill a balloon from

these cylinders and inhale the gas from the balloon. The result was a mild euphoric high that lasted for a few minutes and a sense of well-being that lingered for several hours. Sometimes, there would be a loss of consciousness for a few seconds and an experience of “flying.” Once consciousness returned, there was the possibility of sensory distortions, nausea, or vomiting. Ordinary cans of commercial whipped cream, in which nitrous oxide is the propellant gas, currently provide easy access to this inhalant.

Nitrous oxide itself is a nontoxic gas, but its inhala- tion presents serious risks. As with any euphoriant drug, the recreational use of nitrous oxide can be extremely dangerous when a person is driving under its influence. In addition, if nitrous oxide is inhaled through an anes- thetic mask and the mask is worn over the mouth and nose, without being combined with oxygen, the conse- quences can be lethal. Nitrous oxide dilutes the air that a person breathes. Normally, the oxygen concentration in the air we breathe is 21 percent. If the oxygen con- centration falls below 17 percent, symptoms of hypoxia

Public demonstrations of nitrous oxide (“laughing gas”) inhalation were popular entertainments in the first half of the nineteenth century.

nitrous oxide (NIGH-trus oX-ide): An analgesic gas commonly used in modern dentistry. It is also referred to as laughing gas.

whippets: Small canisters containing pressurized nitrous oxide.

hypoxia (high-PoX-ee-ah): A deficiency in oxygen intake.

Chapter 13 Depressants and Inhalants ■ 329

(literally “oxygen deficiency”) such as light-headedness will result; if the concentration falls below 10 percent, there will be a loss of consciousness. The victim will be either asphyxiated and die or else sustain irreversible brain damge.33

Ether Like nitrous oxide, ether came into use well before its anesthetic effects were appreciated by the medical pro- fession. It was introduced by Friedrich Hoffmann at the beginning of the 1700s, under the name Anodyne, as a liquid “nerve tonic” for intestinal cramps, tooth- aches, and other pains. Whether it was swallowed or inhaled (it evaporated very quickly), ether also produced effects that resembled intoxication from alcohol. In fact, during the mid-1800s, when the com- bination of a heavy tax on alcohol and a temperance campaign in England and Ireland forced people to consider alternatives to alcoholic beverages, both ether drinking and ether inhalation became quite popular. It was used for the same purpose later in the United States during the Prohibition years and in Germany during World War II, when alcohol was rationed. The flammability of ether, however, made its recreational use highly dangerous.34

Glue, Solvent, and Aerosol Inhalation

The abuse of nitrous oxide and ether may have a rela- tively long history, but the more familiar reports of inha- lation abuse involving glue and solvent chemicals have appeared only since the late 1950s.

The common products that have been sub- ject to abuse include glues, paint thinners, lighter fluid, and stain removers. In addition, many aero- sol products are inhalable: hair sprays, deodorants, vegetable lubricants for cooking, and spray paints. Unfortunately, new products are continually being introduced for genuinely practical uses, with little awareness of (or little regard for) the consequences should someone inhale their ingredients on a recre- ational basis (Table 13.4). Significant problems are also associated with occupational exposure to solvent vapors. In a study reported in 1999, 125  pregnant women who had been exposed to solvent prod- ucts at the workplace were studied over a nine-year period. There was a thirteen times greater risk of birth defects among the exposed group, relative to

controls. These women included factory workers, laboratory technicians, artists, printing industry work- ers, chemists, and painters.35

The Abuse Potential of Inhalants Commercial glues, solvents, and aerosol sprays are prime candidates for drug abuse for a number of rea- sons. First, because they are inhaled into the lungs, the feeling of intoxication occurs more rapidly than with orally administered alcohol. “It’s a quicker drunk,” in the words of one solvent abuser.36 The feel- ing is often described as a “floating euphoria,” similar

Table 13.4

Household products with abuse potential and their ingredients

HouseHold ProducT Possible ingredienTs

Glues, plastic cements, and rubber cements

Acetates, acetone, benzene, hexane, methyl chloride, toluene, trichloroethylene

Cleaning solutions Carbon tetrachloride, petroleum products, trichloroethylene

Nail polish removers Acetone

Lighter fluids Butane, isopropane

Paint sprays, paint thinners, and paint removers

Acetone, butylacetate, methanol, toluene, methyl chloride

Other petroleum products

Acetone, benzene, ether, gasoline, hexane, petroleum, tetraethyl lead, toluene

Typewriter correction fluid Trichloroethylene, trichlorethane

Hair sprays Butane, propane

Deodorants, air fresheners Butane, propane

Whipped cream propellants

Nitrous oxide

Sources: Schuckit, M. A. (2006). Drug and alcohol abuse: A clinical guide to diagnosis and treatment (6th ed.). New York: Springer, p. 237. Sharp, C. W., and Rosenberg, N. L. (1997). Inhalants. In J. H. Lowinson, P. R., R. B. Millman, and J. G. Langrod (Eds.), Substance abuse: A comprehensive text- book (3d ed.). Baltimore: Williams and Wilkins, p. 248.

ether (ee-ther): An anesthetic drug first introduced to surgical practice by William T. Morton in the 1840s. It is highly flammable.

330 ■ Part Four Enhancers and Depressants

to the effect of alcohol but with a shorter course of intoxication. The high is over in an hour or so, and the hangover is considered less unpleasant than that following alcohol consumption. Second, the typical packaging of inhalant products makes them easy to carry around and conceal from others. Even if they are discovered, many of the products are so common that it is not difficult to invent an excuse for having them on hand.

Finally, most inhalants are easily available in hard- ware stores, pharmacies, and supermarkets, where they can be bought cheaply or stolen. Among some inhalant abusers, shoplifting these products from open shelves becomes a routine practice. Inhalants are even more widely available than alcohol in poor households; liquor may be in short supply, but gasoline, paints, and aerosol products are usually to be found around the house or garage.37 All these factors contribute to the considerable potential for inhalant abuse.

Acute Effects of Glues, Solvents, and Aerosols The fumes from commercial inhalant products fall into the general category of depressant drugs, in that the central nervous system is inhibited after they are inhaled. Brain waves, measured objectively through an electroencephalograph (EEG), slow down. Subjec- tively, the individual feels intoxicated within minutes after inhalation. The most immediate effects include giddiness, euphoria, dizziness, and slurred speech, last- ing from fifteen to forty-five minutes. This state is fol- lowed by one to two hours of drowsiness and sometimes a loss of consciousness. Along with these effects are occasional experiences of double vision, ringing in the ears, and hallucinations.38

The Dangers of Inhalant Abuse Inhalant abuse often involves concentrations of glue and solvent products that are fifty to a hundred times greater than the maximum allowable concentration of exposure in industry. The health of the inhalant abuser, therefore, is obviously at risk (Health Alert).

The dangers of inhalant abuse lie not only in the toxic effects of the inhaled compound on body organs but also in the behavioral effects of the intoxication itself. Inhalant-produced euphoria includes feelings of recklessness and omnipotence. The hallucinations that are sometimes experienced carry their own personal risks. Walls may appear to be closing in, or the sky may seem to be falling. Ordinary objects may be perceived

to be changing their shape, size, or color. Any one of these delusions can lead to impulsive and potentially destructive behavior.39

There are also significant hazards related to the ways in which inhalants are administered. Solvents are sometimes inhaled from a handkerchief or from the container in which they were originally acquired (“huffing”), but glues and similar vaporous compounds are often squeezed into a plastic bag and inhaled while the bag is held tightly over the nose and mouth (“bag- ging”). As in the case of nitrous oxide abuse, a loss of consciousness can result in hypoxia and asphyxia- tion. Choking can occur if there is vomiting while the inhaler is unconscious. Another danger lies in the

H E A l T H A l E R T !

The Signs of Possible Inhalant Abuse • Headaches and dizziness • Light sensitivity (from dilation of the pupils) • Reddened, irritated eyes and rash around the mouth • Double vision • Ringing in the ears (tinnitus) • Sneezing and sniffling • Coughing and bad breath • Nausea, vomiting, and loss of appetite • Diarrhea • Chest pains • Abnormal heart rhythm (cardiac arrhythmia) • Muscle and joint aches • Slurred speech and unsteady muscle coordination • Chemical odor or stains on clothing or body • Rags, empty aerosol cans and other containers • Plastic and paper bags found in closets and other

hidden places

Where to go for assistance: www.inhalant.org

The web site is sponsored by the National Inhalant Prevention Coalition, Austin, Texas.

Source: Schuckit, M.A. (2006). Drug and alcohol abuse: A clinical guide to diagnosis and treatment (6th ed.). New York: Springer, p. 219.

Chapter 13 Depressants and Inhalants ■ 331

inhalation of Freon, a refrigerant gas so cold that the lar- ynx and throat can be frozen upon contact.Identifying the toxic effects of inhalant drugs is complicated by the fact that most products subject to inhalant abuse con- tain a variety of compounds, and in some cases, the list of ingredients on the product label is incomplete. Therefore, we often do not know whether the medical symptoms resulted from a particular chemical or from its interaction with others. Nonetheless, there are spe- cific chemicals that have known health risks. The most serious concern involves sudden-death cases, brought on by cardiac dysrhythmia, that have been reported fol- lowing the inhalation of propane and butane, which are commonly used as propellants for many commer- cial products.40

Besides butane and propane, other inhalant ingre- dients that present specific hazards are acetone, benzene, hexane, toluene, and gasoline.

■ Acetone: Acetone inhalation causes significant damage to the mucous membranes of the respira- tory tract.

■ Benzene: Prolonged exposure to benzene has been associated with carcinogenic (cancer-producing) dis- orders, specifically leukemia, as well as anemia. Ben- zene is generally used as a solvent in waxes, resins, lacquers, paints, and paint removers.

■ Hexane: The inhalation of hexane, primarily in glues and other adhesive products, has been asso- ciated with peripheral nerve damage leading to muscular weakness and muscle atrophy. There is a latency period of a few weeks before the symptoms appear.

■ Toluene: Toluene inhalation through glue sniffing has been associated with a reduction in short-term memory, anemia, and a loss of hearing, as well as dys- functions in parts of the brain that result in difficul- ties in movement and coordination. Toluene also has been implicated as a principal factor in cases of lethal inhalation of spray paints and lacquers, although it is difficult to exclude the contribution of other solvents in these products.

■ Gasoline: Concentrated vapors from gasoline can be lethal when inhaled. Medical symptoms from gasoline inhalation are also frequently attributed to gasoline additives that are mixed in the fuel. The additive triorthocresyl phosphate (TCP), in par- ticular, has been associated with spastic muscle dis- orders and liver problems. Lead content in gasoline is generally linked to long-term CNS degeneration, but fortunately, leaded gasoline is no longer com- monly available in the United States. On the other

hand, present-day gasoline mixtures contain poten- tially lethal amounts of toluene, acetone, and hex- ane to help achieve the “anti-knock” property that lead had previously provided.41

Patterns of Inhalant Abuse

Among all the psychoactive drugs, inhalants are associ- ated most closely with the young—and often the very young. For those who engage in inhalant abuse, these compounds frequently represent the first experience with a psychoactive drug, preceding even alcohol or tobacco. Overall, inhalant abuse ranks fourth high- est in drug experimentation among secondary school students, surpassed only by alcohol, tobacco, and mari- juana (in that order). Most of those who engage in inhalant abuse, however, are younger than secondary school age; often they are between eleven and thirteen years old.

The University of Michigan survey of 2011 found that about 13 percent of eighth-grade students had used inhalants at some previous time. About 7 percent reported that they had used inhalants within the past year, and 3 percent within the past month. Inhalants are the only class of drugs for which the incidence of usage in the eighth grade significantly exceeds the incidence in the tenth and twelfth grades.

Evidently, awareness of this form of drug-taking activity is quite extensive in the later elementary and middle school student population. According to a recent survey, almost two-thirds of ten- to seventeen- year-olds know the meaning of “huffing” and report

acetone (ASS-eh-tone): A chemical found in nail polish removers and other products.

benzene: A carcinogenic (cancer-producing) com- pound found in many solvent products, representing a serious health risk when inhaled.

hexane: A dangerous compound present in many glues and adhesive products. Inhalation of these products has been associated with muscle weakness and atrophy.

toluene (Tol-yoo-ene): A compound in glues, cements, and other adhesive products. Inhalation of these products results in behavioral and neurological impairments.

triorthocresyl phosphate (TCP) (tri-oR-thoh-CREH-sil FoS-fate): A gasoline additive. Inhalation of TCP- containing gasoline has been linked to spastic muscle disorders and liver problems.

332 ■ Part Four Enhancers and Depressants

that they were about twelve years of age when they first became aware of classmates abusing inhalants.42

In other cultures and under different circumstances, inhalant abuse affects even younger children and a greater proportion of them. In Mexico City, among street children as young as eight or nine who live with- out families in abandoned buildings, rates of inhalant abuse are extremely high; 22 percent report engaging in some form of solvent inhalation on a daily basis. Inhal- ant abuse is reported to be commonplace among street children in Rio de Janeiro and other major cities in Central and South America as well as Asia (Drugs . . . in Focus).43

Inhalant abuse on an experimental basis is not restricted by social or geographic boundaries. Chronic inhalant abuse, however, is overrepresented among the poor and those youths suffering emo- tional challenges in their lives and seeking some form of escape. Studies of young inhalant abusers show high rates of delinquency, poor school perfor- mance, and emotional difficulties. They often come from disorganized homes in which the parents are actually or effectively absent or else engage in abuse of alcohol or some other substance themselves.44

High prevalence rates for inhalant abuse exist among such disparate groups as Latino children in a rural community in the Southwest, American Indian children on a U.S. reservation, and white children

Drugs . . . in Focus

Resistol and Resistoleros in Latin America In the cities of Central and South America, the street children are referred to as resistoleros, a name derived from their frequent habit of sniffing a commercial brand of shoemaker’s glue called Resistol. Granted, many cases of inhalant abuse among the hundreds of thousands of chil- dren in Latin America do not specifically involve Resistol; nevertheless, the frequency of Resistol abuse and the fact that Resistol dominates the market in commercial solvent- based adhesives have focused attention on the company that manufactures it, the H. B. Fuller Company of St. Paul, Minnesota.

Concern for the welfare of these children also has spotlighted a thorny ethical issue: Should a corporation accept the social responsibility when widespread abuse of its product exists, either in the United States or else- where in the world? Testor Corporation in 1969 added a noxious ingredient to discourage abuse of its model-kit

glue; in 1994, a German chemical company marketing a Resistol rival halted its distribution in this region. For its part, Fuller did modify the formulation of Resistol in 1992, replacing the sweet-smelling but highly toxic toluene with a slightly less toxic chemical, cyclohexane. However, it continues to sell Resistol, claiming that its legitimate uses benefit the economies of regions where it is marketed. Moreover, the company has funded community programs for homeless children throughout Central America and has limited its Resistol marketing efforts to large indus- trial customers, rather than marketing to small retailers. Unappeased, foes continue to press Fuller to discontinue the product entirely.

Note: There is no connection between Resistol glue and Resistol Western Hats or any corporation-related sponsor- ships such as the Resistol Arena in Mesquite, Texas.

Source: Henriques, D.B. (1995, November 26). Black mark for a “good citizen.” Critics say H. B. Fuller isn’t doing enough to curb glue-sniffing. New York Times, Section 3, pp. 1, 11.

A group of abandoned Brazilian children inhale glue from bags in Rio de Janeiro. Their dazed expression is a typical sign of inhalant intoxication.

Chapter 13 Depressants and Inhalants ■ 333