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Chapter 6

Stimulants

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Stimulants are substances that can keep a person going, both mentally and physically

Restricted stimulants:

Examples: cocaine and amphetamine

Readily available stimulants:

Examples: caffeine and nicotine

Stimulants

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Image Source: Janne Tervonen/Alamy

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Coca

A bush that grows in the Andes and produces cocaine

Harvested for thousands of years and actively cultivated for over 800 years

The coca leaf was an important part of Inca culture

Used in religious ceremonies and as currency

Some natives of the Andes still chew coca leaves to reduce fatigue and increase productivity

Cocaine History

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Cocaine was in use in Europe by the 19th century

Coca wine

Developed by Angelo Mariani

Used coca leaf extract in many other products including lozenges and tea

Cocaine History

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Image source: National Library of Medicine, National Institutes of Health (Image Ch06_06CocaWine)

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Cocaine was also used in the United States in early versions of Coca-Cola and in many patent medicines

Cocaine History

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Image source: National Library of Medicine, National Institutes of Health (Image Ch06_07CocaineDrops)

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Cocaine was isolated from the plant before 1860

Processing 500 kilograms of coca leaves yields
1 kilogram of cocaine

Medical use:

Dr. W. S. Halsted experimented with cocaine as a local anesthesic

Delivered via newly developed hypodermic syringe

“Father of modern surgery”

Cocaine History

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Early psychiatric uses:

Sigmund Freud studied use of cocaine as a treatment for depression and morphine dependence

Later opposed use of the drug after nursing a friend through cocaine psychosis

Cocaine History

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Press and politicians made unsubstantiated claims about cocaine use among southern blacks:

Widespread use

Associated with increased violent crime

46 states passed laws to regulate cocaine between 1887 and 1914

Negative racially-charged publicity about cocaine helped shape American drug policy

Early Legal Controls on Cocaine

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Coca paste

Crude extract created during the manufacture of cocaine

In South America, often mixed with tobacco and smoked

Cocaine hydrochloride

Most common form of pure cocaine

Stable water-soluble salt

Often insufflated

Forms of cocaine

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Freebase

Extraction of the cocaine base with a solvent (ether)

Can be heated and the vapors inhaled

Crack cocaine

Lumps of cocaine base prepared by mixing cocaine with water and baking soda

Can be heated and the vapors inhaled

Important Note: Powder and crack are the same drug

Cocaine base is the active ingredient in all forms of cocaine

Forms of Cocaine

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Cocaine use increased in the late-1960s

Prior to 1985, the major form of the drug available was cocaine hydrochloride

Most often insufflated

Usually sold in bulk amounts that were relatively expensive

Cocaine use was associated with status, wealth, and fame

By the mid-1980s, crack became available

Relatively inexpensive ($5 to $10 a hit)

Smoked cocaine use was associated with poor, black Americans

Contemporary Legal Controls

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Media and politicians focused on crack use among urban black Americans

Associated with violence and dependency

Anti-Drug Abuse Act of 1986

Penalties for sale of crack cocaine significantly more severe compared with powder cocaine

Tougher penalties for first-time users of crack

U.S. Sentencing Commission concerns about policy:

Penalties’ severity disproportionately impacted blacks

Exaggerated relative harmfulness of crack

Contemporary Legal Controls

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Federal Cocaine Offenders (by Race)

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Cocaine’s mechanism of action is complex

Cocaine blocks reuptake of dopamine, serotonin, and norepinephrine

GABA and glutamate have also been implicated

Mechanism of Action

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Figure 6.1 from text

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Chewing or sucking coca leaves

Slow absorption and onset of effects

Insufflation

“Snorting”

Absorbed through nasal mucous membranes

Rapid absorption and onset of effects

Intravenous injection

Rapid and brief effects

Smoked

Rapid and brief effects

Absorption and Onset of Effects

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Cocaine is metabolized by enzymes in the blood and liver

Half-life of about one hour

Major metabolites have a half-life of eight hours

These are detected by urine drug screens

It takes about 3 days for metabolites to be completely eliminated after moderate use

Cocaine Elimination

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Local anesthesia:

Used medically since 1884

Early applications were eye surgery and dentistry

Synthesized drugs with few CNS effects have largely replaced cocaine

Cocaine remains in use for surgery in the nasal, laryngeal, and esophageal regions

Beneficial Uses

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No evidence that occasional use of small amounts is detrimental to health

Potential toxicity increases with larger doses

Profound CNS stimulation

which can lead to respiratory or cardiac arrest

Illicit cocaine is often adulterated

Adulterants may be more toxic than the drug

Concerns: Acute Toxicity

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Binge use

Drug is taken repeatedly and at increasingly high doses

Risks of binge use

Increasing irritability, restlessness, paranoia

Can result in paranoid psychosis

Most seem to recover once the drug leaves the system

Concern: Chronic Toxicity

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Image source: McGraw-Hill Companies, Inc./Gary He, photographer

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Cocaine addiction occurs in some users

Animal and human studies have shown that cocaine is a powerfully reinforcing drug

Example: Animals will readily self-administer the drug by lever-pressing

After binge use, some people experience withdrawal symptoms

Cocaine craving, irritability, anxiety, depressed mood, increased appetite, fatigue

Concerns: Dependence Potential

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“Crack Baby” phenomenon

Media reports overstated the expected long-term effects of cocaine exposure

Recent studies indicate no consistent associations between cocaine exposure and several developmental measures

Cocaine use during pregnancy

Increased risk of miscarriage and torn placenta

Concerns: Reproductive Effects

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Image source: S. Meltzer/PhotoLink/Getty Images (Image Ch06_16CocaineInfant)

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Readily available in all major U.S. cities

Price and purity have remained stable for the past decade

Most illicit cocaine in the U.S. comes from:

Peru, Bolivia, and Columbia

Supplies of Illicit Cocaine

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NSDUH and MTF surveys indicate:

Less than 1 percent of adults currently use cocaine (2012 data)

Down from a peak of 12 percent in the 1980s

In general, usage rates of cocaine and amphetamine tend to cycle in opposition to each other

When cocaine use decreases, amphetamine use may increase

Current Patterns of Use

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The Chinese used a medicinal tea made from ma huang (Ephedra)

Amphetamines History

Active ingredient is ephedrine

Stimulates the sympathetic branch of the autonomic nervous system

Sympathomimetic drug

Used to treat asthma

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Image source: © Spike Mafford/Getty Images

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Amphetamine

Synthesized chemical similar to ephedrine

Patented in 1932

Early medical uses:

Asthma

Narcolepsy

Hyperactivity in children

Appetite suppressant

Stimulant

Amphetamines History

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Wartime uses:

Increased efficiency and reduced fatigue

1960s “speed scene”

Many IV drug users used amphetamines either alone or in combination with heroin (speedball)

Most street amphetamines came from prescriptions

Amphetamines became more tightly controlled, leading to:

Increased cocaine use

Increased illicit manufacture of methamphetamine

Amphetamines History

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Illicit manufacture of methamphetamine is dangerous and associated with toxic fumes and residue

The drug often contains impurities that may be toxic

Methamphetamine abuse rose in the Western and Midwestern United States throughout the 1990s

Increases in Eastern U.S. cities were relatively modest

Cocaine remains the stimulant of choice

The Return of Methamphetamine

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Chemical structure of amphetamine is similar to the catecholamine neurotransmitters

Causes increased activity of monoamine neurotransmitters by stimulating their release

dopamine, norepinephrine, serotonin

The structure of methamphetamine allows it to easily cross the blood-brain barrier

Ephedrine is less able to cross the barrier

Thus, produces more peripheral and fewer central nervous system effects

Amphetamine Pharmacology

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Peak effects

1.5 hours after oral ingestion

5-20 minutes after intranasal administration

5-10 minutes following intravenous injection or smoking

Half-life

5-12 hours

Completely eliminated in approximately 2–3 days

Rapid tolerance (tachyphylaxis) can occur after high doses

Absorption and Elimination

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Depression

Treatment of choice during the 1950s–60s

Now used as an adjunctive therapy

Major advantage = antidepressant effects occur relatively rapidly

Weight control

In the 1960s, widely used to reduce food intake and body weight for short periods of time

Methamphetamine currently FDA-approved

Long-term effects on obesity unclear

Beneficial Uses

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Figure 6.3 from text

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Narcolepsy

Uncontrolled daytime episodes of muscular weakness and falling asleep

Stimulants used to keep patients awake during the day

“Smart pills”

At a low level of arousal, may improve performance

At a high level of arousal, may decrease performance

Athletics

Under some circumstances, may produce slight improvements in athletic performance

Beneficial Uses

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Methamphetamine Effects on Performance

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Figure 6.3 from text

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Treatment of Attention-Deficit Hyperactivity Disorder (ADHD)

Characterized by problems with inattention, hyperactivity, and impulsivity

Stimulant medications can reverse catecholamine-associated deficits that may underlie ADHD

Concerns about abuse and side effects has lead to other treatment options

However, data suggest that stimulant is protective against substance abuse

Beneficial Uses

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Acute behavioral toxicity

Increases in feelings of power, suspicion, paranoia

In animals, very high doses may destroy catecholamine neurons

Caveat: dosing regimens used in animal studies do not mimic those used by humans

Concerns: Acute Toxicity

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Paranoid psychosis following binge use

Possible reasons for psychosis include:

Heavy methamphetamine users may have schizoid personalities

Primarily due to sleep deprivation

No good evidence for permanent behavioral or personality disruption

Concerns: Chronic Toxicity

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Can produce psychological dependence in some individuals

As defined by DSM criteria

A potent reinforcer in animals and humans

Abuse potential is likely dose-dependent

Low to moderate doses for medical use rarely lead to dependence

Concerns: Dependence Potential

or distribution without the prior written consent of McGraw-Hill Education.

Image Source: Janne Tervonen/Alamy

Image source: National Library of Medicine, National Institutes of Health (Image Ch06_06CocaWine)

Image source: National Library of Medicine, National Institutes of Health (Image Ch06_07CocaineDrops)

Figure 6.1 from text

Image source: McGraw-Hill Companies, Inc./Gary He, photographer

Image source: S. Meltzer/PhotoLink/Getty Images (Image Ch06_16CocaineInfant)

Figure 6.3 from text