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Lecture 8

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PSYC 3403
Tarry Ahuja

Lecture 8 Overview - Tetrahydrocannabinol (THC) • Pharmacokinetics • Pharmacological effects • Tolerance and dependence • Therapeutic uses Cannabis - Hemp plant, Cannabis sativa - Also known as cannabis, marijuana, or ganja - Psychoactive compounds produced: • Delta-9-tetrahydrocannabinol (THC) • Cannabinol • Cannabidiol - Hashish: dried portions of the female flower • High potency; 10-20% - Ganja: dried tops of the female flower • Medium potency; 5-8% - Marijuana: dried remainder of the plant • Low potency; 2-5% • Improved growing 30% Cannabis (history) - Used for thousands of years - Ancient Hindus of India and Nepal - Used in religious and cultural ceremonies - Today used primarily for recreational usage - Still considered an illicit substance - Many believe marijuana should be legal - Canada made medical usage legal - Several US states have followed - 1920’s portrayed as a “evil” drug - Laws were passed banning its use - 1930’s looked on as a “narcotic” - 1940’s public convinced it was a “killer drug” - Still considered an illicit substance Cannabis (routes of administration) - Cigarette (joint): dried marijuana buds are mixed with tobacco and rolled into cigarette - Cigar (blunt): slice open and replace with marijuana - Pipe: higher level of drug entry - Bong: water pipes which increase concentration of THC - Food: baked in brownies or added to teas Cannabis (mechanism) **DON’T NEED TO KNOW** - THC was isolated as the active ingredient THC (mechanism) - 1990 THC receptor was isolated - G protein-coupled receptor: • Inhibits adenylate cyclise • Binds THC • Binds other cannabinoids - Found on the presynaptic nerve terminal (CB1) THC (mechanism) - Activation causes: 2+ • Inhibition of Ca entry • Facilitates K channels - As a result, inhibits release of other NTs • Presynaptic GABA release - Body has an endogenous cannabinoid: anandamide Anandamide - Binds to the cannabinoid receptor - Weaker agonist than THC - Both are partial agonists (interact with binding site, but not perfectly) - Activates 50% of available receptors (THC activates ~20%) Cannabinoid receptors - Found throughout the brain - Basal ganglia and cerebellum: • Movement and posture - Frontal cortex: • Psychoactive effects (senses, time) - Hippocampus: • Memory, memory storage THC (pharmacokinetics) - Low content and release through administration - Joint: • 75mg of THC present • 25mg available in smoke • 5-10mg absorbed into blood stream - Can also be taken orally dronabinol (marinol) • Slower onset, first-pass metabolism • Only 10-20% dose reaches bloodstream • Produces active metabolite with a prolonged half-life (11 hydroxy-delta-8-THC), 4-6 hours - The “high” is achieved quickly - Effects last between 2-3 hours - Readily passes through BBB, placental barrier - Metabolism of active metabolite produces inactive metabolite, carboxy-THC - Half-life of 30-60 hours, biomarker DA“reward” pathway THC (pharmacological effects) - Analgesic properties (helps with pain) - Decreases body temperature - Calms aggressive behavior - Temporal distortions - Memory impairments - Increased appetite/weight gain - Acute memory impairments are paired with decreased blood flow - Dose-dependent loses in memory, IQ - Heavy-users show parallel substance abuse THC (tolerance and dependence) - 2 mechanisms of dependence: • Down-regulation of cannabinioid receptors (fewer so that effect is muted, so people need to take more. Signs of tolerance) • Receptor internalization (minor) - Marijuana withdrawal syndrome • Depressed mood • Insomnia • Lower food intake • Irritability THC (therapeutic uses) - Dronabinol (Marinol) used as an: • Appetite stimulant forAIDS patients • Anti-nauseant for against “chemo” • Reduce intra-occular pressure - Other unverified uses have been suggested Cannabinoid antagonists - Provides a dose-dependent blockade of marijuana induced intoxication - Assist in marijuana abstinence - Enhancement of learning and memory - Assist in controlling obesity Overview - Psychedelics • History • Classification • Pharmacoki
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