The Cannabis PlantCannabis PreparationsHashishSinsemillaMarijuana HistoryU.S. RegulationMarijuana Tax Act of 1937After the Marijuana Tax ActCannabinoid ChemicalsPharmacologyMechanism of ActionCardiovascular EffectsOther Psychological EffectsPulmonary effectsBehavioral EffectsCognitive EffectsAcuteChronicMedical Uses of CannabisDronabinolState and Federal ActionAbuse and DependenceToleranceWithdrawalToxicity PotentialChapter 15: Marijuana The Cannabis Plant- 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 RussiaCannabis Preparations- 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 stalksHashish- Most potent preparation- In its purest form it consists of pure resin that has been carefully removed from the surface of leavesand stems- Relatively rare in the U.S. About 1% of confiscated marijuana samplesSinsemilla- 2nd most potent preparation Consists of dried flowering tops of plantswith pistillate flowers (i.e., female plants) Average THC content is 11%- Smokable marijuana in U.S., can vary widely in potency fromMarijuana History- 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 murderso Origin of the word “assassin” Hashish use mentioned frequently in The Arabian Nights U.S. Regulation- 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 evidenceMarijuana Tax Act of 1937- 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 unconstitutionalAfter the Marijuana Tax Act- 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 1990sCannabinoid Chemicals- 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-THCPharmacology- After smoking THC is absorbed rapidly by the blood and travels to the brain and then 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 weeksMechanism of Action- THC binds to two receptorsCB1 receptors CB2 receptors- Found primarily in the brain but also throughout the body- Found mainly outside the brain in immune cells- High density in specific brain regions Basal ganglia and cerebellum (movement coordination) Hippocampus (memory storage) Cerebral cortex (higher cognitive functions) Nucleus accumbens (reward)- Potential role of cannabinoids in the modulation of the immune systemCardiovascular Effects- Dose-dependently increases heart rate Time course differs depending on route of administrationOther Psychological Effects- Reddening of the eyes- Dryness of the mouth and throat Pulmonary effects- Acute: Few effects on breathing- Chronic: Heavy marijuana smoking over a long period could lead to clinically significant impairment of pulmonary function Behavioral Effects- Self-administration Studies show both animals and humans will self-administer both 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- Subjective effects Euphoria, “high,” mellowness, hunger, and stimulation Infrequent users experience similar but more intense effects compared with 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 increaseCognitive EffectsAcute- 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 effectsChronic- 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 cognitionMedical Uses of Cannabis- 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 can’t be injected Oral dose has delayed onset of action - 1970s–present: renewed interest in medical uses Glaucoma Cancer treatment-related nausea Dronabinol- Dronabinol (Brand Name: Marinol) Oral THC preparation- Used as an antiemetic 1985: