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Chapter 15

Marijuana

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Marijuana is a preparation of leafy material from the Cannabis plant that is usually smoked

Three species:

Cannabis sativa: used primarily for its fibers from which hemp rope is made

Cannabis indica: grown for its psychoactive resins

Cannabis ruderalis: grows primarily in Russia

The Cannabis Plant

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delta-9-tetrahydrocannabinol (THC)

Primary psychoactive agent in Cannabis

THC is concentrated in the resin

Potency of Cannabis preparations depends on the amount of resin present

Most of the resin is in the flowering tops

Less in the leaves

Little in the fibrous stalks

Cannabis Preparations

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Hashish

Most potent preparation

In its purest form it consists of pure resin that has been carefully removed from the surface of leaves and stems

Relatively rare in the U.S.

About 1% of confiscated marijuana samples

Cannabis Preparations

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Image source: Drug Enforcement Administration (Image Ch15_10Hashish)

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Sinsemilla

2nd most potent preparation

Consists of dried flowering tops of plants
with pistillate flowers (i.e., female plants)

Average THC content is 11%

Smokable marijuana in U.S., can vary widely in potency from

Cannabis Preparations

1% THC (low-grade product)

11% THC (high-grade sinsemilla)

About 50% of confiscated marijuana is sinsemilla

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Image Source: Drug Enforcement Administration

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Earliest mention 2737 BC: Chinese pharmacy book

Recommended several medical uses

1000 AD: Social use of the plant had spread to the Muslim world and North Africa

“Hashishiyya” religious cult carried out political murders

Origin of the word “assassin”

Hashish use mentioned frequently in The Arabian Nights

Marijuana History

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1926:

Series of newspaper articles linked marijuana and crime

Public interest increased

1936:

All states had laws regulating the use, sale, and/or possession of marijuana

Most early regulation efforts

Based on concerns about use and criminal behavior

Concerns not based on direct evidence

Marijuana History: U.S. Regulation

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Followed the regulation-by-taxation theme of the 1914 Harrison Act

Grower, distributor, seller, and buyer were taxed

Result: administratively almost impossible to deal in Cannabis

State laws made possession and use illegal

1969: U.S. Supreme Court declared the Marijuana Tax Act unconstitutional

Marijuana Tax Act of 1937

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Cost of marijuana increased significantly

LaGuardia Report (1944):

Concluded that marijuana use had less serious effects than commonly believed

Report elicited strong negative reactions

Use of marijuana increased throughout the 1950s–1960s

Use peaked in 1970s

Marijuana use decreased in the 1980s

But rose again in the 1990s

After the Marijuana Tax Act

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Chemistry of Cannabis is complex

More than 400 chemicals in marijuana

About 70 are cannabinoids

delta-9-tetrahydrocannabinol (THC)

The most pharmacologically active cannabinoid

synthesized in 1964

Major active metabolite is 11-hydroxy-delta-9-THC

Cannabinoid Chemicals

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Cannabinoid Chemicals

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Figure 15.1 in text

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After smoking

THC is absorbed rapidly by the blood and travels to the brain and then to the rest of the body

Peak mood-altering and cardiovascular effects occur within 5 to 10 minutes

After oral administration

THC is absorbed more slowly

Peak effects occur about 90 minutes following ingestion

Metabolism

THC has a half-life of 19 hours

Complete elimination of THC and its metabolites may take 2–3 weeks

Pharmacology

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THC binds to two receptors

CB1 receptors

Found primarily in the brain but also throughout the body

High density in specific brain regions

Basal ganglia and cerebellum (movement coordination)

Hippocampus (memory storage)

Cerebral cortex (higher cognitive functions)

Nucleus accumbens (reward)

CB2 receptors

Found mainly outside the brain in immune cells

Potential role of cannabinoids in the modulation of the immune system

Mechanism of Action

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Dose-dependent increases heart rate

Time course differs depending on route of administration

Cardiovacular Effects

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Figure 15.2

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Reddening of the eyes

Dryness of the mouth and throat

Other Physiological Effects

Pulmonary effects

Acute:

Few effects on breathing

Chronic:

Heavy marijuana smoking over a long period could lead to clinically significant impairment of pulmonary function

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Image source: Doug Menuez (Image Ch15_14SmokingMarijuana1)

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Self-administration

Studies show both animals and humans self-administer smoked marijuana and oral THC

Under controlled laboratory conditions:

Marijuana cigarettes with higher THC content are preferred

Participants choose more oral THC during periods of social interaction

Data indicate:

The abuse potential of THC

Cannabis self-administration is influenced by social factors

Behavioral Effects

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Subjective effects

Euphoria, “high,” mellowness, hunger, and stimulation

Infrequent users experience similar but more intense effects compared to experienced smokers

At high THC concentrations, infrequent users may report negative effects such as mild paranoia

Food intake

Marijuana and oral THC significantly increase total daily calorie intake

Verbal behavior

Verbal exchanges decrease

nonverbal social interactions increase

Behavioral Effects

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Infrequent users: marijuana disrupts cognitive performance

Slowed cognitive processing

Impaired short-term memory

Impaired inhibitory control

Loss of sustained concentration or vigilance

Impaired visuospatial processing

Frequent users: marijuana causes less dramatic effects

Slowed cognitive processing

Frequent users may be tolerant to cognitive effects

Cognitive Effects: Acute

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Difficult to make definitive statements about effects on long-term cognitive functioning

Studies have had divergent findings and interpretations

Current evidence suggests that

after abstaining for more than a month, regular marijuana use produces few effects on cognition

Cognitive Effects: Chronic

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Medical use declined before the 1937 Marijuana Tax Act for several reasons:

New and better drugs were developed to treat most illnesses

Variability of product

Active ingredient insoluble in water and thus cannot be injected

Oral dose has delayed onset of action

1970–present: renewed interest in medical uses

Glaucoma

Cancer treatment-related nausea

Medical Uses of Cannabis

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Dronabinol (Brand Name: Marinol)

Oral THC preparation

Used as an antiemetic

1985: FDA-approved for sale to cancer patients experiencing nausea from chemotherapy

Used to stimulate appetite

1993: FDA-approved for sale to AIDS patients

Dronabinol

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Failure of currently approved medications

Symptoms will be relieved by a rapid onset

Treatment is under medical supervision

Oversight strategy for dispensation

Legal medical use as of early 2014:

23 states and DC have legislation allowing medical use

Medical Use: State and Federal Action

1999: Institute of Medicine issued report that recommended use of marijuana when certain conditions are met:

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Image source: The McGraw-Hill Companies, Inc./Lars A. Niki, photographer (Image Ch15_19PotisMedicineSign)

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Tolerance

Tolerance to many marijuana effects develops after high levels of regular use

May not develop uniformly to all effects

Withdrawal

DSM-5: No listing of cannabis withdrawal

Research suggests a withdrawal syndrome does exist

Not life threatening but unpleasant

Begins about 1 day after the last dose

Lasts 4 to 12 days

Symptoms include anxiety, irritability, disrupted sleep, decreased food intake

Abuse and Dependence

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Acute physiological effects

Increased heart rate

Possibly risky for someone with preexisting cardiovascular disease

However, no human overdose deaths have been reported

Chronic lung exposure

Most recent research indicates that marijuana is not associated with respiratory symptoms or lung disease

Marijuana smoke contains many of the carcinogens found in tobacco smoke

Not yet clear whether marijuana smokers are at an increased risk for cancer

Toxicity Potential

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Reproductive effects

Reduced testosterone levels in men

Diminished sperm counts and abnormal sperm structure in men

Marijuana use by pregnant women does not appear to be associated with negative birth outcomes

Immune system effects

Findings have been mixed

Some evidence that suggests that marijuana use reduces immunity to infection

Mortality data do not show a relationship between marijuana use and overall death rate

Toxicity Potential

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Anxiety

Characterized by fear of loss of control

Some people seek medical treatment (e.g., sedatives)

The best treatment is likely “talking down”

Amotivational syndrome

Laboratory data do not support the hypothesis that frequent marijuana smokers exhibit diminished motivation

Driving ability

Laboratory studies: significant impairment in infrequent users

Epidemiological studies: little evidence for impairment

Toxicity Potential

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Marijuana Madness

Some studies have found a correlation between marijuana use and psychotic symptoms

Causation

Psychotic symptoms prior to using marijuana

Influence of other drug use on the psychotic symptoms

There is evidence that marijuana can increase the likelihood of psychotic episodes

in individuals with a history of psychiatric problems

Toxicity Potential

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