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Chapter 11. Oldest non-food crop cultivated by man/woman  Originated in central Asia  Cultivated & dispersed before written history  2700 BC - first.

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Presentation on theme: "Chapter 11. Oldest non-food crop cultivated by man/woman  Originated in central Asia  Cultivated & dispersed before written history  2700 BC - first."— Presentation transcript:

1 Chapter 11

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

7 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  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  Leaves, stems and flowering buds of cannabis sativa  Most of the THC is in the buds

10 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 Hash Oil - boil with solvent, solvent then strained out  THC concentration as high as 60% - 70%  Becoming more popular - ease of smuggling

12 Paper Plastics Fuels Textiles Animal Bedding Mulch Bird seed Flour and cereals Body care products Non diary milk/cheese Nut butter Salad dressing Sports Bars/ Protein Powder Margarine Paints/ Varnishes Detergents Industrial hemp Incense

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

14  Cannabidiol - slows metabolism of THC increase duration  converted to THC when burned  may have neuroprotective, anticonvulsant and anti-psychotic effects ◦

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

16 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  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 CB-1 Receptor CB-2 Receptor  Mostly in periphery  Found primarily in immune system  Found on heart – protects from inflammation? o Located in CNS and PNS

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21 Red = abundant CB 1 receptor expression Black = moderately abundant CB 1 receptor expression

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

24  Psychotomimetic ◦ Pseudo hallucinations ◦ Synesthesias ◦ Paranoia ◦ Agitation ◦ Disorganized thoughts ◦ Confusion  Impaired executive function ◦ Increased impulsivity ◦ Impaired judgment, slower RT ◦ Pronounced motor deficits

25 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.

26  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

27  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

28  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

29  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

30  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

31  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

32  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

33  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

34  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

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