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Marijuana/Cannabis

Marijuana/Cannabis. Chapter 11. History of Marijuana. Oldest non-food crop cultivated by man/woman Originated in central Asia Cultivated & dispersed before written history 2700 BC - first written record in China Used for medicinal properties. History of Marijuana.

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Marijuana/Cannabis

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  1. Marijuana/Cannabis Chapter 11

  2. History of Marijuana Oldest non-food crop cultivated by man/woman • Originated in central Asia • Cultivated & dispersed before written history • 2700 BC - first written record in China • Used for medicinal properties

  3. History of Marijuana • Major cannabis spread about 200 BC with Scythians • warlike Middle Eastern tribe, gave us word “cannabis” • used in cleansing ceremony after funerals • threw hemp seeds on heated rocks inside tents & inhaled vapors

  4. History of Marijuana • Hebrews also used cannabis (Old Testament in Exodus) • God told Moses to make holy oil containing cannabis • Most infamous use by Muslim sect founded by Hasan-Sabbah (Hashishin) • secret assassination • gave us words hashish & assassin

  5. History of Marijuana • France in mid 1800s with "Club des Hachichins" • writer Gautier offered reward to anyone who invented a new pleasure – was given hashish by a doctor • Victor Hugo, Alexander Dumas • consumed large quantities of hash-like material • wrote accounts of their experiences

  6. History of Marijuana • In U.S., primarily for rope (George Washington) • Introduced by Mexican laborers in early 1900s (group targeted by 1st laws) • 1920s & 1930s - major attention - drug of violent crime & danger to society • Commissioner of Narcotics, Harry Anslinger -crusade against marijuana

  7. History of Marijuana 1937 Marijuana Tax Act • made possession of marijuana without having paid special tax illegal Early 1940s • NYC Mayor Fiorello La Guardia • set up commission of experts to determine consequences of marijuana use • Final report - marijuana fairly minor intoxicant with few side effects even when used excessively • Report ridiculed by Anslinger

  8. History of Marijuana • Marijuana comeback: late 1950s to early 1960s • Now most broadly used illicit substance in U.S. • 35-40% of Americans having tried • Numerous states have compassionate use laws

  9. Preparations of Marijuana • Leaves, stems and flowering buds of cannabis sativa • Most of the THC is in the buds

  10. Preparations of Marijuana Hashish - processing of plant to yield dried resin - more concentrated THC content • resins scraped/ plants harvested (female) • beaten down/ rolled in carpets/ leaf substance collected and placed in tubs containing alcohol • evaporated off • pressed into bars • content 5% - 20%

  11. Preparations of Marijuana Hash Oil - boil with solvent, solvent then strained out • THC concentration as high as 60% - 70% • Becoming more popular - ease of smuggling

  12. Industrial hemp Incense Various Uses

  13. Active Agents -9-THC -8-THC Cannabidiol Active Metabolites

  14. Active Agents • Cannabidiol - slows metabolism of THC increase duration • converted to THC when burned • may have neuroprotective, anticonvulsant and anti-psychotic effects

  15. Pharmacokinetics • Absorption • Smoking – rapid and complete • Oral – Half that of smoking • Distribution • Everywhere as it is highly lipophilic • Flies across BBB • Administration • Inhalation – Smoke • Oral – Tincture, Eating, Tea • Marinol • Oral-mucosal • Sativex

  16. Metabolism & Clearance • Binds to proteins and fats • Slow metabolism in liver • Metabolites for a week – three weeks • Primary metabolic product is more potent • (11-OH- 9-THC) • Delay between peak plasma levels and “high”

  17. Mechanism of Action • Mostly unknown until the late 1980s • 1988 – Isolated the receptors • 1992 – Discovered the first neurotransmitter for that receptor • THC binds to cannabinoid receptors • It’s and Agonist • Anandamide & 2-AG are the NTs for cannabinoid receptors • Works as a retrograde NT • It modulates the activity of many neurotransmitters • This is way it has such broad effects

  18. Two Receptor Types • Mostly in periphery • Found primarily in immune system • Found on heart – protects from inflammation? • Located in CNS and PNS CB-1 Receptor CB-2 Receptor

  19. Red = abundant CB1 receptor expressionBlack = moderately abundant CB1 receptor expression

  20. Low - Moderate Doses • STM impairment • Balance impaired • Decreased muscle strength • Small tremor • Poor on complex tasks (e.g., driving) • Disinhibition • Relaxation • Drowsiness • Exhilaration, euphoria • Sensory - perceptual changes • Overestimate time passage

  21. Higher Doses • Impaired executive function • Increased impulsivity • Impaired judgment, slower RT • Pronounced motor deficits • Psychotomimetic • Pseudo hallucinations • Synesthesias • Paranoia • Agitation • Disorganized thoughts • Confusion

  22. Physiological Effectsof Marijuana Physiological effects • Increase in pulse rate & slight drop in BP • Produces dry mouth & occasional dizziness • Reddening of eyes (dilation of vessels in cornea) • No permanent adverse cardiovascular • People with heart disease should abstain • Increased risk for heart attack four an hour after smoking • Appetite increased • Hypothalamus • “Hedonic Hotspot” – specific area of NAC when stimulated by cannabinoids there is an increase in the reward value of natural rewards.

  23. Side Effects of Marijuana • THC suppresses immune system, but not enough to increase risk of infection it appears. • Lowers testosterone levels & sperm count as well as estrogen • Crosses placental barrier • Lower birth weight • Some evidence suggests a relation between mother smoking while pregnant and childhood cancer • Most severe side effects • Respiratory - can lead to asthma & bronchitis • Anxiety/panic in some users

  24. THC Toxicity • Almost impossible to OD • 1-1.8 kg w/5% taken orally in a female • THC not toxic in this sense • Pot smoke contains more tar than cigarette smoke • Does one smoke the same? • Cancer and respiratory possibilities • Data on cancer is very mixed – recent studies show no relationship • THC found to kill cultured hippocampal cells, but so far not in other cells high in CB receptor density • Effect reversed with NSAIDS • Possible mechanism for memory loss

  25. THC – Tolerance & Dependence • Tolerance develops with heavy long-term use • Reverse tolerance in consistent users • Cross tolerance with sedatives - alcohol • Dependence – mild (like SSRIs) • Mild withdrawal symptoms in humans, with irritability, depression, sleep disturbances, nausea, diarrhea, sweating, tremors, reduced food intake, and salivation • 50% of heavy users may experience it • 30 mg THC / 4 hrs / 10-20 days (unusual levels of intake) • Begin within 48 hours after cessation and lasts 2 – 10 days

  26. Highly Debated Effects • Amotivational Syndrome • Most research has not found this to be true • Is it a HOST effect? • It may be psychopathology independent of use • Gateway Drug • Most well-designed studies suggest this is false. • “Common liability model” is a better explanation • Alcohol and cigarettes are stronger gateway drugs if one accepts the data

  27. Medical Marijuana • Many states have compassionate use laws • California, Washington, Oregon, Nevada, Alaska, Vermont, Maine, Colorado, New Mexico, Montana, Rhode Island, Maryland • Physicians “recommend” marijuana and patient buy it at buyers clubs. • Would lose license if prescribed • 2003 Gallup Pole – 75% for medical use, 66% against legalization • 2005 study of physicians'’ attitudes • 36 % were in favor of legal prescription • 26% were neutral

  28. Medical Marijuana • 1998 IOM report concluded that there is scientific evidence for the medical use of marijuana • Analgesic – Next slide • Anti-emetic • Anti-spastic • Appetite Stimulant • Glaucoma • Tumor suppression (lung cancer) • Siezures? – THC & Cannibidiol protect against neurotoxicity • Cannabinoid Antagonists? - Ramonabant

  29. THC and Analgesia • Likely mediated through CNS/PNS mechanism as well as non-NS systems • RVM – Part of brainstem • THC increases activity of pain suppressing neurons and decreases activity of pain enhancing neurons • Inhibits glutamate release • Increases dynorphin release • CB receptors located on peripheral sensory nerves • Reduce pain signaling from the site of “damage” • Inhibits prostaglandin synthesis

  30. How to administer THC • Studies show smoking is superior to oral administration of either synthetic or natural THC • Significant problems w/smoking however • Tar and toxins • Respiratory problems • Cancer? – Want to make sure it’s not an issue • Vaporizers • Heat pot to 180-200 degrees • Releases active drugs, but does not produce toxins • Sativex – THC spray • Delivered as a mist • Used in Western Europe and Canada • Studies are positve

  31. Medical Marijuana • The Empirical View……. • There is a medical use for THC • Medical use does not require legalization • You can be anti-drug and pro-medicalization • Saying there is no medical value is a statement based in either politics or ignorance/stupidity • There are ways to get the gains of smoked THC without smoking • Like many other medicines, there are risks and the a potential for abuse

  32. The debate continues

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