Marijuana

1. Marijuana Chapter 11 • Cannabis sativa • Tetrahydrocannabinol (THC)

2. History of Marijuana Oldest non-food crop cultivated by man/woman • Earliest archaeological records from Taiwan, 10,000 yr (stone age) evidence of hemp fiber use • Pottery, clothes, shoes, bow strings, paper (105 A.D.) • Ts’ai Lun ridicule! • Use Spread throughout Asia, the mid East, and eventuallyEurope.

3. History of Marijuana- Religious and Medical use • Also originating in China…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. Early History • India • Bhang--tea • Ganja—pipe • Charas--hashish/hash

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

6. 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

7. History of Marijuana • In Early U.S., primarily for rope and canvas (George Washington), Minor medicinal use • Prohibition increased use of MJ..NYC “Tea Pads!”

9. The Bureau of Narcotics • Commissioner of Narcotics, Harry Anslinger -crusade against marijuana • 1920s & 1930s - major attention - drug of violent crime & danger to society

10. History of Marijuana 1937 Marijuana Tax Act • made possession of marijuana without having paid special tax illegal • classified marihuana as a controlled substance. Needless to say most doctors and dentists stopped using products covered by this law.

11. What we have lost

12. Industrial hemp Incense Various Uses

13. History of Marijuana 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

14. A harder attitude- 1950’s-60’s • VI. THE 1950's: HARSHER PENALTIES AND A NEW RATIONALE-THE "STEPPING STONE" THEORY • 1951 Congress passed -the Boggs Act . .much harsher penalties for all drug violators. marijuana and other narcotics were lumped together • First offense 2 - 5 years • Second offense 5 - 10 years • Third and subsequent offenses 10 - 20 years • Fine for all offenses $2,000.00 Boggs stated: "We need only to recall what we have read in the papers in the past week to realize that more and more younger people are falling into the clutches of unscrupulous dope peddlers . . . .“ Perhaps Commissioner Anslinger best described the prevailing climate when he stated: • Short sentences do not deter. In districts where we get good sentences the traffic does not flourish.... • There should be a minimum sentence for the second offense. The commercialized transaction, the peddler, the smuggler, those who traffic in narcotics, on the second offense if there were a minimum sentence of 5 years without probation or parole, I think it would just about dry up the traffic

16. 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

17. Marijuana use exploded in the 1960s

18. And use continued at high rates into the 70’s through today

19. Time/CNN Poll 2006 • 80% approve of medical use of marijuana • 72% say that marijuana possession should lead to fine, not jail • 47% say that they have tried marijuana at least once

23. A changing Attitude? Law Reforms: • 2006, Recreational Marijuana use on ballot in Colorado and Nevada • Defeated in both cases • January 02, 2009 MassachusettsOn Nov. 4, a majority of voters in Massachusetts chose to decriminalize possession of small amounts of marijuana. Those in possession of less than an ounce of marijuana are no longer charged with a criminal offense, but instead face a $100 fine.

24. U.S. Drug laws TODAY

25. The International perspective-The Dutch Experience • Marijuana is NOT legal, but laws are not enforced for Coffee shops in Amsterdam • Over 1000 shops are now licensed in the Netherlands • Cannot advertise • Cannot sell to minors

27. Current MJ World Laws

28. The Future?/ Politics of Marijuana

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

30. Cannabis Preparations

31. 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

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

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

34. Pharmacokinetics • Administration • Inhalation – Smoke • Oral – Tincture, Eating, Tea • Marinol • Oral-mucosal • Sativex • Distribution • Everywhere as it is highly lipophilic • Flies across BBB To meet demands for Sativex, GW Pharmaceuticals has increased production of cannabis at its fortified greenhouses to 60t/y. (Source: ABPI)

35. Pharmacokinetics of THC • Rapid absorption in lung • 2-4 hr duration of action • Erratic absorption after oral admin. • Great persistence in tissue: up to 30 days after a single dose • Detection in urine 10-14+ days after a single dose; >21 days after chronic use • Distribution • Everywhere as it is highly lipophilic • Flies across BBB

36. Metabolism & Clearance • Binds to proteins and fats • Slow metabolism in liver • Metabolites remain detectable for a week – three weeks • Primary metabolic products may be more potent • (11-OH- 9-THC)

37. Mechanism of Action • Mostly unknown until the late 1980s • 1988 – Isolated the receptors • 1992 – Discovered the first neurotransmitter for that receptor • THC binds to and agonizes cannabinoid receptors • Anandamide & 2-AG are the NTs for cannabinoid receptors • Anandamide : The brain’s own marijuana (from Ananda: Hindu word for bliss) • Works as a neuromodulator/ and “retrograde NT”

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

40. CB1 receptor hot spots

41. THC is a retrograde CB1 agonist- works on the presynaptic terminal to modulate NT release

42. Physiological Effectsof Marijuana Physiological effects • Increase in HR & drop in BP • Produces dry mouth & occasional dizziness • Reddening of eyes (dilation of vessels in cornea) • No permanent adverse cardiovascular effects • People with heart disease should abstain • Increased risk for heart attack four an hour after smoking • Appetite increased • May be related to actions on the Hypothalamus • or nucleus accumbens- when stimulated by cannabinoids there is an increase in the reward value of natural rewards.

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

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

45. 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

46. THC Toxicity • Almost impossible to OD • THC not toxic in this sense • Pot smoke contains more tar than cigarette smoke Data on cancer is very mixed – recent studies show no relationship Does one smoke the same? • 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

47. 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 • 5% of heavy users may experience it • 30 mg THC / 4 hrs / 10-20 days 15+ joints per day (unusual levels of intake) • Begin within 48 hours after cessation and lasts 2 – 10 days

48. Highly Debated Effects • Amotivational Syndrome • Amotivational Syndrome is a theoretical condition that proposes the heavy use of marijuana may alter a smoker’s motivations, goals, and possibly personality. • Most research has not found this to be true • When it appears to exist, It may be psychopathology independent of use

49. What is Amotivational Syndrome? • Amotivational Syndrome is a theoretical condition that proposes the heavy use of marijuana may alter a smoker’s motivations, goals, and possibly personality. • Better put, this syndrome may cause "... apathy, loss of effectiveness, and diminished capacity or willingness to carry out complex, long-term plans, endure frustration, concentrate for long periods, follow routines, or successfully master new material. Verbal facility is often impaired both in speaking and writing. Some individuals exhibit greater introversion, become totally involved with the present at the expense of future goals and demonstrate a strong tendency toward regressive, childlike, magical thinking.“ – McGlothin, W.H.

50. History of Amotivational Syndrome • The 1960’s are associated with an explosion of the use of marijuana. • Peak use was surveyed in 1979 with 24 million smokers. • Before this time, any record of amotivational syndrome was completely nonexistent.