Transcript Drugs, Society, and Human Behavior

Marijuana
CANNABIS SPECIES
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Cannabis sativa
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Cannabis indica
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grows worldwide
Tall plant with long, thin light green leaves
used for fibers to make cloth and rope, but also
used for psychoactive properties.
Plentiful in Mideast, India, and Central Asia
Short plant with broad dark leaves
Mainly used for psychoactive resins.
Cannabis ruderalis
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grows primarily in Eastern Europe (Russia,
Poland)
Short weedy plant, less THC content than others
CANNABIS
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Primary psychoactive agent in Cannabis
delta-9-tetrahydrocannabinol (THC)
Various preparations from Cannabis
 Charas (in India) or Hashish
 the pure resin from the leaves and stems
 avg. concentration of THC is 3% to 7%, as high as
20%
 Ganja (in India) or Sinsemilla (Spanish, without seeds)
 dried tops of female plants (without seeds)
 THC concentration 7 – 12%
 Bhang
 dried, ground up remainder of the plant
 avg. concentration of THC is 1% to 2%
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Early History of Cannabis
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Cannabis probably originated in central Asia
 Cultivated
and widely dispersed before
recorded history.
 Scythians were probably responsible for
spreading its use to Egypt and north to Europe
and Russia.
 In China, Cannabis probably known since
~4000 B.C.
 Cultivated for fiber, seed, as well as intoxicating
and medicinal properties.
 Social use began in North Africa by ~1000 A.D.
Recent History of Cannabis Use
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Widespread industrial use of hemp in
western Europe and American colonies
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psychoactive properties not widely
recognized until 19th century
19th Century: Romantic Literature and the
New Science of Psychology
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Use expanded into Europe and was widespread
among artists and writers.
The new science of psychology also introduced
the use and study of psychoactive agents.
HISTORY
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“Marijuana, Assassin of Youth”
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Sensationalized stories in the news media
e.g., blaming marijuana for violent crimes
36 states in U.S. had laws regulating the use, sale
and/or possession of marijuana by 1935.
 The
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Marijuana Tax Act of 1937
Did not outlaw Cannabis, but taxed it
After the Marijuana Tax Act
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New York Academy study showed no
physical or mental deterioration with longterm use.
PHARMACOLOGY
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Cannabinoid Chemicals
 Over 400 chemicals in marijuana
 61 unique to the cannabis plant
 called cannabinoids
Pharmacokinetics
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THC is a weak acid with a pKa of 10.6
 not ionized at pH of bodily fluids
When smoked, rapid absorption
 Peak effects within 5-10 min.
When ingested, peak effects ~90 min.
Half-life ~ 19 hours, longer for metabolites (20-30 hrs)
 Main metabolite: 11-hydroxy-delta-9-THC, which
may be more active than delta-9-THC
NEUROPHARMACOLOGY
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Mechanisms of Action
 CB receptors discovered in brain, 1990
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CB1 receptors: in CNS
 primarily in cortex, hippocampus, cerebellum,
basal ganglia
CB2 receptors: spleen, immune system
Endocannabinoids were discovered soon after .
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Anandamide, 2-arachidonylglycerol (2-AG)
Neuromodulators of multiple neurotransmitters,
including monoamines, GABA, ACh and endorphins
 Signaling between postsynaptic and presynaptic
cells
 Interactions with opioid peptides to modulate DA
transmission in mesolimbic structures
Acute Physiological Effects
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Cardiovascular and Peripheral Effects
 Increased heart rate
 Variable effects on blood pressure
 Dry mouth, “bloodshot” eyes
Effects on Sleep
 Drowsiness, increased sleep time
 High doses can produce insomnia.
Cognitive/Behavioral Effects
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Low to moderate doses produce euphoria,
a pleasant state of relaxation, laughter
Some loss of coordination and balance
Simple reaction times relatively unaffected
Complex and choice reaction time,
accuracy but not speed affected.
Impaired short-term memory
Reduced sustained attention
Impaired visuo-spatial and temporal
processing
Adverse Behavioral Effects
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Moderate to high doses may produce mild
anxiety to panic and paranoia
A few rare cases have been reported of
cannabis-induced psychoses, delusional
and bizarre behavior, and hallucinations
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These reactions occur most frequently in
individuals who are under stress, anxious,
depressed or borderline schizophrenic.
Driving Performance
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The ability to perform complex tasks, such
as driving, may be impaired while under
the influence of marijuana.
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Laboratory studies with non-regular marijuana
users show significant impairments.
Results suggest that marijuana has little effect
on ability to control a car, but impairs the
driver’s ability to attend to peripheral stimuli.
Effects of THC on driving ability are amplified
when combined with alcohol.
Critical Thinking Skills
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Marijuana has been found to have a
negative impact on critical thinking skills.
Impairment can affect: attention, memory,
learning.
An unresolved question is whether these
impairments are due to acute drug effects
or long-term consequences of regular use.
Behavioral Effects in Nonhumans
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Unconditioned Behavior
 Biphasic effect on motor activity; initial increase, then
depressant effects.
 Stimulatory effects represent an exaggerated response
to environmental stimuli.
 High doses produce ataxia.
 Reduced aggressive behavior
Conditioned Behavior
 Interference with tasks that assess short term
memory
 THC decreases avoidance responding, like depressants
 Unlike depressants, THC does not increase punished
behavior.
Behavioral Effects in Nonhumans
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Drug Discrimination
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Self-Administration
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Rats readily learn to discriminate THC
Some evidence for partial generalization to
depressants, but not to any other drug classes
THC discrimination is blocked by CB1 antagonists.
Due to low solubility in water, I.V. self-administration
of THC has been difficult to study.
Water soluble synthetic cannabinoids are selfadministered.
THC also establishes Conditioned Place
Preference in rats.
Health Risks
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Abuse/Dependence Potential
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Tolerance occurs when high levels are used
over long periods.
Physical dependence has been observed
under certain heavy use conditions.
Psychological dependence does not occur
for most users, but can occur with frequent
heavy use.
Withdrawal symptoms occur within 1 day
and persist 4-12 days
 Anxiety, restlessness, depression,
irritability, disrupted sleep, decreased
food intake, sometimes increased
aggression
Health Risks
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Chronic Lung Exposure
 Similar chemicals to tobacco
 Levels of exposure differ from tobacco
 Marijuana as a causal factor in COPD or
lung cancer is still debated
Reproductive Effects
 Effects noted but significance not known
Immune System Effects
 No relationship established between
marijuana use and overall death rate
MEDICAL USES OF CANNABIS
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China
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First mention in 2737 B.C. was medical use
Cannabis mixed with wine was used for anesthetic
2900 years later (A.D. 200)
Europe
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Almost no mention until 1800s
1839, W.B. O’Shaughnessy reported on
anticonvulsant and appetite stimulant effects.
Several publications followed regarding numerous
other medical uses (e.g., tetanus, neuralgia,
dysmenorrhea, asthma, gonorrhea, migraine,
alcohol addiction).
MEDICAL USE OF CANNABIS
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United States
Some early medicinal use in 1800s
 Minimal uses until Marijuana Tax Act of
1937 resulted in withdrawal of existing
products
 Renewed interest following a 1972 report
showed help for glaucoma patient and a
1975 report noted reduced nausea in
chemotherapy patients.
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MEDICAL USE OF CANNABIS
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Suggested medical uses of marijuana
include
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Reduced intraocular pressure
Antiemetic
Appetite stimulant
Pain management
Reduced muscle spasticity
Recent developments with synthetic
derivatives of THC (e.g., Marinol) and
oral preparations from cannabis extracts
(e.g., Savitex).