Marijuana

MarijuanaMarijuana

CANNABIS SPECIESCANNABIS SPECIES Cannabis sativaCannabis sativa

grows worldwidegrows worldwide Tall plant with long, thin light green leavesTall plant with long, thin light green leaves used for fibers to make cloth and rope, but also used for fibers to make cloth and rope, but also

used for psychoactive properties.used for psychoactive properties.

Cannabis indicaCannabis indica Plentiful in Mideast, India, and Central AsiaPlentiful in Mideast, India, and Central Asia Short plant with broad dark leavesShort plant with broad dark leaves Mainly used for psychoactive resins. Mainly used for psychoactive resins.

Cannabis ruderalis Cannabis ruderalis grows primarily in Eastern Europe (Russia, grows primarily in Eastern Europe (Russia,

Poland)Poland) Short weedy plant, less THC content than othersShort weedy plant, less THC content than others

CANNABISCANNABIS Primary psychoactive agent in Cannabis Primary psychoactive agent in Cannabis

delta-9-tetrahydrocannabinol (THC)delta-9-tetrahydrocannabinol (THC) Various preparations from Various preparations from CannabisCannabis

Charas (in India) or HashishCharas (in India) or Hashish the pure resin from the leaves and stemsthe pure resin from the leaves and stems avg. concentration of THC is 3% to 7%, as high as avg. concentration of THC is 3% to 7%, as high as

20%20% Ganja (in India) or Sinsemilla (Spanish, without seeds)Ganja (in India) or Sinsemilla (Spanish, without seeds)

dried tops of female plants (without seeds)dried tops of female plants (without seeds) THC concentration 7 – 12%THC concentration 7 – 12%

BhangBhang dried, ground up remainder of the plant dried, ground up remainder of the plant avg. concentration of THC is 1% to 2%avg. concentration of THC is 1% to 2%

Early History of CannabisEarly History of Cannabis Cannabis probably originated in central AsiaCannabis probably originated in central Asia

Cultivated and widely dispersed before Cultivated and widely dispersed before recorded history.recorded history.

Scythians were probably responsible for Scythians were probably responsible for spreading its use to Egypt and north to Europe spreading its use to Egypt and north to Europe and Russia.and Russia.

In China, Cannabis probably known since In China, Cannabis probably known since ~4000 B.C.~4000 B.C.

Cultivated for fiber, seed, as well as intoxicating Cultivated for fiber, seed, as well as intoxicating and medicinal properties.and medicinal properties.

Social use began in North Africa by ~1000 A.D.Social use began in North Africa by ~1000 A.D.

Recent History of Cannabis Recent History of Cannabis UseUse

Widespread industrial use of hemp in Widespread industrial use of hemp in western Europe and American colonieswestern Europe and American colonies psychoactive properties not widely psychoactive properties not widely

recognized until 19recognized until 19thth century century 19th Century: Romantic Literature and the 19th Century: Romantic Literature and the

New Science of PsychologyNew Science of Psychology Use expanded into Europe and was widespread Use expanded into Europe and was widespread

among artists and writers.among artists and writers. The new science of psychology also introduced The new science of psychology also introduced

the use and study of psychoactive agents.the use and study of psychoactive agents.

HISTORYHISTORY ““Marijuana, Assassin of Youth”Marijuana, Assassin of Youth”

Sensationalized stories in the news mediaSensationalized stories in the news media e.g., blaming marijuana for violent crimese.g., blaming marijuana for violent crimes 36 states in U.S. had laws regulating the use, 36 states in U.S. had laws regulating the use,

sale and/or possession of marijuana by 1935.sale and/or possession of marijuana by 1935.

The Marijuana Tax Act of 1937The Marijuana Tax Act of 1937 Did not outlaw Did not outlaw CannabisCannabis, but taxed it, but taxed it

After the Marijuana Tax ActAfter the Marijuana Tax Act New York Academy study showed no New York Academy study showed no

physical or mental deterioration with long-physical or mental deterioration with long-term use.term use.

PHARMACOLOGYPHARMACOLOGY Cannabinoid ChemicalsCannabinoid Chemicals

Over 400 chemicals in marijuanaOver 400 chemicals in marijuana 61 unique to the 61 unique to the cannabiscannabis plant plant

called cannabinoidscalled cannabinoids PharmacokineticsPharmacokinetics

THC is a weak acid with a pKa of 10.6THC is a weak acid with a pKa of 10.6 not ionized at pH of bodily fluids not ionized at pH of bodily fluids

When smoked, rapid absorptionWhen smoked, rapid absorption Peak effects within 5-10 min.Peak effects within 5-10 min.

When ingested, peak effects ~90 min.When ingested, peak effects ~90 min. Half-life ~ 19 hours, longer for metabolites (20-30 hrs)Half-life ~ 19 hours, longer for metabolites (20-30 hrs)

Main metabolite: 11-hydroxy-delta-9-THC, which Main metabolite: 11-hydroxy-delta-9-THC, which may be more active than delta-9-THCmay be more active than delta-9-THC

NEUROPHARMACOLOGYNEUROPHARMACOLOGY Mechanisms of Action Mechanisms of Action

CB receptors discovered in brain, 1990CB receptors discovered in brain, 1990 CB1 receptors: in CNSCB1 receptors: in CNS

primarily in cortex, hippocampus, cerebellum, primarily in cortex, hippocampus, cerebellum, basal gangliabasal ganglia

CB2 receptors: spleen, immune systemCB2 receptors: spleen, immune system Endocannabinoids were discovered soon after .Endocannabinoids were discovered soon after .

Anandamide, 2-arachidonylglycerol (2-AG)Anandamide, 2-arachidonylglycerol (2-AG) Neuromodulators of multiple neurotransmitters, Neuromodulators of multiple neurotransmitters,

including monoamines, GABA, ACh and endorphinsincluding monoamines, GABA, ACh and endorphins Signaling between postsynaptic and presynaptic Signaling between postsynaptic and presynaptic

cellscells Interactions with opioid peptides to modulate DA Interactions with opioid peptides to modulate DA

transmission in mesolimbic structurestransmission in mesolimbic structures

Acute Physiological EffectsAcute Physiological Effects

Cardiovascular and Peripheral Cardiovascular and Peripheral EffectsEffects Increased heart rateIncreased heart rate Variable effects on blood pressureVariable effects on blood pressure Dry mouth, “bloodshot” eyesDry mouth, “bloodshot” eyes

Effects on SleepEffects on Sleep Drowsiness, increased sleep timeDrowsiness, increased sleep time High doses can produce insomnia.High doses can produce insomnia.

Cognitive/Behavioral EffectsCognitive/Behavioral Effects Low to moderate doses produce Low to moderate doses produce

euphoria, a pleasant state of euphoria, a pleasant state of relaxation, laughterrelaxation, laughter

Some loss of coordination and balanceSome loss of coordination and balance Simple reaction times relatively unaffectedSimple reaction times relatively unaffected Complex and choice reaction time, accuracy Complex and choice reaction time, accuracy

but not speed affected.but not speed affected. Impaired short-term memoryImpaired short-term memory Reduced sustained attentionReduced sustained attention Impaired visuo-spatial and temporal Impaired visuo-spatial and temporal

processing processing

Adverse Behavioral EffectsAdverse Behavioral Effects Moderate to high doses may produce Moderate to high doses may produce

mild anxiety to panic and paranoiamild anxiety to panic and paranoia A few rare cases have been reported A few rare cases have been reported

of cannabis-induced psychoses, of cannabis-induced psychoses, delusional and bizarre behavior, and delusional and bizarre behavior, and hallucinationshallucinations These reactions occur most frequently in These reactions occur most frequently in

individuals who are under stress, individuals who are under stress, anxious, depressed or borderline anxious, depressed or borderline schizophrenic.schizophrenic.

Driving PerformanceDriving Performance

The ability to perform complex tasks, The ability to perform complex tasks, such as driving, may be impaired while such as driving, may be impaired while under the influence of marijuana.under the influence of marijuana. Laboratory studies with non-regular Laboratory studies with non-regular

marijuana users show significant marijuana users show significant impairments.impairments.

Results suggest that marijuana has little Results suggest that marijuana has little effect on ability to control a car, but impairs effect on ability to control a car, but impairs the driver’s ability to attend to peripheral the driver’s ability to attend to peripheral stimuli.stimuli.

Effects of THC on driving ability are Effects of THC on driving ability are amplified when combined with alcohol.amplified when combined with alcohol.

Critical Thinking SkillsCritical Thinking Skills

Marijuana has been found to have a Marijuana has been found to have a negative impact on critical thinking skills.negative impact on critical thinking skills.

Impairment can affect: attention, Impairment can affect: attention, memory, learning.memory, learning.

An unresolved question is whether these An unresolved question is whether these impairments are due to acute drug impairments are due to acute drug effects or long-term consequences of effects or long-term consequences of regular use.regular use.

Behavioral Effects in Behavioral Effects in NonhumansNonhumans

Unconditioned BehaviorUnconditioned Behavior Biphasic effect on motor activity; initial increase, Biphasic effect on motor activity; initial increase,

then depressant effects.then depressant effects. Stimulatory effects represent an exaggerated Stimulatory effects represent an exaggerated

response to environmental stimuli.response to environmental stimuli. High doses produce ataxia.High doses produce ataxia. Reduced aggressive behaviorReduced aggressive behavior

Conditioned BehaviorConditioned Behavior Interference with tasks that assess short term Interference with tasks that assess short term

memorymemory THC decreases avoidance responding, like THC decreases avoidance responding, like

depressantsdepressants Unlike depressants, THC does not increase Unlike depressants, THC does not increase

punished behavior.punished behavior.

Behavioral Effects in Behavioral Effects in NonhumansNonhumans

Drug DiscriminationDrug Discrimination Rats readily learn to discriminate THCRats readily learn to discriminate THC Some evidence for partial generalization to Some evidence for partial generalization to

depressants, but not to any other drug classes depressants, but not to any other drug classes THC discrimination is blocked by CB1 antagonists.THC discrimination is blocked by CB1 antagonists.

Self-AdministrationSelf-Administration Due to low solubility in water, I.V. self-Due to low solubility in water, I.V. self-

administration of THC has been difficult to study.administration of THC has been difficult to study. Water soluble synthetic cannabinoids are self-Water soluble synthetic cannabinoids are self-

administered.administered. THC also establishes Conditioned Place THC also establishes Conditioned Place

Preference in rats.Preference in rats.

Health RisksHealth Risks Abuse/Dependence PotentialAbuse/Dependence Potential

Tolerance occurs when high levels are used Tolerance occurs when high levels are used over long periods.over long periods.

Physical dependence has been observed Physical dependence has been observed under certain heavy use conditions.under certain heavy use conditions.

Psychological dependence does not occur Psychological dependence does not occur for most users, but can occur with frequent for most users, but can occur with frequent heavy use.heavy use.

Withdrawal symptoms occur within 1 day Withdrawal symptoms occur within 1 day and persist 4-12 daysand persist 4-12 days Anxiety, restlessness, depression, Anxiety, restlessness, depression,

irritability, disrupted sleep, decreased irritability, disrupted sleep, decreased food intake, sometimes increased food intake, sometimes increased aggressionaggression

Health RisksHealth Risks Chronic Lung ExposureChronic Lung Exposure

Similar chemicals to tobaccoSimilar chemicals to tobacco Levels of exposure differ from tobaccoLevels of exposure differ from tobacco Marijuana as a causal factor in COPD or Marijuana as a causal factor in COPD or

lung cancer is still debatedlung cancer is still debated Reproductive EffectsReproductive Effects

Effects noted but significance not knownEffects noted but significance not known Immune System EffectsImmune System Effects

No relationship established between No relationship established between marijuana use and overall death ratemarijuana use and overall death rate

MEDICAL USES OF MEDICAL USES OF CANNABISCANNABIS ChinaChina

First mention in 2737 B.C. was medical useFirst mention in 2737 B.C. was medical use CannabisCannabis mixed with wine was used for anesthetic mixed with wine was used for anesthetic

2900 years later (A.D. 200)2900 years later (A.D. 200)

EuropeEurope Almost no mention until 1800sAlmost no mention until 1800s 1839, W.B. O’Shaughnessy reported on 1839, W.B. O’Shaughnessy reported on

anticonvulsant and appetite stimulant effects.anticonvulsant and appetite stimulant effects. Several publications followed regarding numerous Several publications followed regarding numerous

other medical uses (e.g., tetanus, neuralgia, other medical uses (e.g., tetanus, neuralgia, dysmenorrhea, asthma, gonorrhea, migraine, dysmenorrhea, asthma, gonorrhea, migraine, alcohol addiction).alcohol addiction).

MEDICAL USE OF MEDICAL USE OF CANNABISCANNABIS

United StatesUnited States Some early medicinal use in 1800sSome early medicinal use in 1800s Minimal uses until Marijuana Tax Act of Minimal uses until Marijuana Tax Act of

1937 resulted in withdrawal of existing 1937 resulted in withdrawal of existing productsproducts

Renewed interest following a 1972 report Renewed interest following a 1972 report showed help for glaucoma patient and a showed help for glaucoma patient and a 1975 report noted reduced nausea in 1975 report noted reduced nausea in chemotherapy patients.chemotherapy patients.

MEDICAL USE OF MEDICAL USE OF CANNABISCANNABIS Suggested medical uses of Suggested medical uses of

marijuana includemarijuana include Reduced intraocular pressureReduced intraocular pressure AntiemeticAntiemetic Appetite stimulantAppetite stimulant Pain managementPain management Reduced muscle spasticityReduced muscle spasticity

Recent developments with synthetic Recent developments with synthetic derivatives of THC (e.g., Marinol) and derivatives of THC (e.g., Marinol) and oral preparations from cannabis extracts oral preparations from cannabis extracts (e.g., Savitex).(e.g., Savitex).