Marijuana

1. Marijuana ADDICTION MEDICINE EDUCATIONAL SERIES WORKBOOK

2. Marijuana STEVEN KIPNIS, MD, FACP, FASAM MEDICAL DIRECTOR OASAS ROBERT KILLAR, CASAC DIRECTOR COUNSELOR ASSISTANCE PROGRAM OASAS KAITLYN PICKFORD, MA FELLOW – CENTER FOR WOMEN IN GOVERNMENT AND CIVIL SOCIETY GOVERNMENT AFFAIRS OFFICE OASAS

3. FLOWERING PLANTS • There are 250,000 – 350,000 species of flowering plants • We have tested most of them • Medicinal value • Poisons • Psychoactive • Religious ceremonies • Magic • Initiation into puberty • Escape reality • Fashionable • Social pleasure

4. FLOWERING PLANTS • Psychoactive substances are found in various parts of the plant • Resin • Fleshy fruit • Stems • Leaves • Seeds • Roots

5. FLOWERING PLANTS • Psychoactive substances can be introduced into the body by • Eating • Drinking (teas) • Smoking • Inhalation • Ointments • Enemas

6. FLOWERING PLANTS • Psychoactive substances are usually members of the chemical class • Alkaloids • Contain nitrogen • Many are toxic • Some are teratogenic (can interfere with normal embryonic development) • Indole rings • 8 carbon atoms and 1 nitrogen • Same structure is seen in serotonin • This group may interfere with serotonin in the brain

7. CANNABIS FAMILY • Cannabaceae contains two genera • Cannabis • Humulus (hop plant) • Resin used as a preservative and as a natural flavor in beer

8. CANNABIS • Known as cannabis, hashish, hemp and marijuana • Source of: • Strong fiber for rope and paper • Nutritious fruit • Industrial oil • Medicine • Cannabis Sativa is a fiber plant • Cannabis Indica is a resin plant

9. CANNABIS • Male and female plants • Female plants are better resin producers • If female plant is not allowed to be fertilized, it flowers but does not produce seeds – sinsemilla (spanish for “without seeds”) • Greatest resin producers

10. CANNABIS • Resin contains • Hallucinogenic compounds called cannabinoids • Delta-1 Tetrahydrocannabinol, also known as • Delta-1-THC • THC • Major active compound in the cannabis plant

11. CANNABIS • How is it used? • Leaves and flowering tips are dried • Smoked • Consumed as tea • Mixed into food • Resin from flowering heads • Smoked • Mixed with tobacco • Alcohol extract (cannabis oil) is mixed with tobacco and smoked

12. CANNABIS HISTORY • 4,000 BC - used as a medicine • Rheumatism – loss of yin (female energy) • 2,700 BC - Chinese emperor said “liberator of sin - good for female weakness, gout, rheumatism, malaria, beri beri, constipation and absent-mindedness”

13. CANNABIS HISTORY • 1,400 BC - in India used to treat anxiety • Bhang (drink from leaves) • Ganja (dried resin) • 1,200 BC - found in a Chinese burial site, also used for bow strings and paper (mixed with mulberry bark)

14. CANNABIS HISTORY • First century AD • Chinese use it to treat constipation, malaria and absent-mindedness • Greeks use it to treat earaches and as a pleasurable dessert made from the seeds • Indian physicians used it for treatment of fever, insomnia, appetite stimulation, headaches and sexually transmitted diseases

15. CANNABIS HISTORY • 200 A.D. Chinese use it as anesthesia for operations • 13th century, Marco Polo learned of a band of thugs in Iran whose leader controlled his followers using hashish. These murderers were called hashishins which was modified to assassins later on.

16. CANNABIS HISTORY • Folk medicine in Europe • Germany - to treat seizures, aid in childbirth • Poland - for toothache (seeds put on hot stones and vapors inhaled) • Czechoslovakia - to treat fever • Russia - to treat jaundice • Serbia - as an aphrodisiac

17. CANNABIS HISTORY • Pilgrims grew it for fiber: ropes and clothing • 1843 U.S. Medical text, treatment for • Gout • Tetanus • Hysteria • Depression • Insanity • Dysentery

18. CANNABIS HISTORY Sumo wrestler with hemp belt which is part of the ritual to cleanse the ring prior to a match

19. CANNABIS HISTORY • 1850 listed in US pharmacopoeia • Abolished use in 1937 Marijuana Tax Act • 1951 Bogg’s Act • Increased penalties for marijuana use because it was thought to lead to heroin addiction • 1956 Narcotics Act • Imposed mandatory prison sentences for cannabis possession • 1965 THC first isolated

20. CANNABIS HISTORY • 2003 - 75 million people in the US have tried marijuana at least once (34% of population) • DAWN* data of emergency room visits show marijuana is number 1, alcohol number 2 and cocaine number 3 • New hydroponically grown marijuana with increased THC levels • Age of onset of use declining from 16 year old to 13.6 year olds • Brain is still not completely developed *The Drug Abuse Warning Network (DAWN) is a public health surveillance system that monitors drug-related hospital emergency department visits and drug-related deaths to track the impact of drug use, misuse and abuse in the U.S.

21. ER VISITS VS. POTENCYCAUSE AND EFFECT?

22. CANNABINOIDS 60 cannabinoids have been isolated from the hemp plant and there are naturally occurring cannabinoids in most species called endocannabinoids, in a similar fashion as endorphins (opiates) have been found.

23. CANNABINOIDS • There are two main receptors for cannabinoids in humans • CB1(in brain) if stimulated produces • Euphoria • Impaired short term memory and sense of time • CB2 (in spleen, peripheral sites) if stimulated produces • Immunosuppressant activity • Not psychoactive

24. CANNABINOIDS • Receptors have also been found in the • Cerebellum – body movement and coordination • Cortex – higher cognitive functions • Nucleus accumbens – reward • Basal ganglia – movement control • Hypothalamus – body temperature, salt and water balance, reproductive functions • Amygdala – emotional responses, fear

25. CANNABINOIDS • Receptors have been found in the hippocampus - an area that controls food intake • Works through leptin system – a peptide that controls satiety • A defect in the leptin or endocannabinoid system may lead to obesity

26. SPECT SCANHEATHLY SURFACE VIEWS TOP DOWN VIEW UNDERSIDE VIEW

27. SPECT SCANTHC Abuse A SPECT scan showing the underside of the brain with area that is showing no activity

28. CANNABINOIDS Cannabis use in the adolescent is highly correlated with subsequent alcohol use.

29. PREPARATION OF CANNABIS • Marijuana • Not a single drug but a complex mixture of over 400 chemicals • Dried flowering tops and leaves of the plant • THC concentration 0.5% - 5% in the past, now up to 20 – 25% Dried cannabis buds

30. PREPARATION OF CANNABIS • Hashish – dried cannabis resin and flowers • THC concentration, 2 - 8% or higher Pieces of Hash

31. PREPARATION OF CANNABIS • Hash oil – extraction of THC from hashish with an organic solvent • THC concentration 15 - 50%

32. CANNABIS • Routes of marijuana administration • Joints • Average is 500 mg of marijuana inside of rolling papers • 20% - 50% of the THC makes it into the bloodstream • Blunts (marijuana in hollowed out cigar) • 6 times the amount of marijuana • 20% of the THC makes it into the bloodstream

33. CANNABIS • Routes of marijuana administration • Pipes • Stone, ceramic or glass • 50% of the THC makes it into the bloodstream • Water pipes • Bongs – most efficient • 90% of the THC makes it into the bloodstream

34. PREPARATION OF CANNABIS • “Fry” / “fry sticks” / “wets” / “wac” • Marijuana soaked in embalming fluid or formaldehyde • In NYC, it has been reported that marijuana has been cooked in butter and spread on toast

35. CANNABIS KINETICS • THC • Noncrystalline • Waxy liquid at room temperature • (-) Trans-isomer is 6 to 100 times more potent than (+) trans-isomer • Psychoactive effect when bound to CB1 receptor

36. CANNABIS KINETICS • THC mechanism of action • Peripheral and central effect • Low dose • Mixture of depression and stimulation • High dose • CNS depression

37. CANNABIS KINETICS • Typical joint • 0.5 - 1 gram cannabis • THC concentration 5 - 150mg • 20 to 70% of THC is delivered in the smoke • 2 - 3 mg THC can produce a brief high • Lipid soluble so deposited into fat tissue

38. CANNABIS KINETICS • 80 probable biologically inactive metabolites of THC • 11-hydroxy - THC is the primary active metabolite • THC is eliminated in the feces and 33% in the urine

39. CANNABIS KINETICS • Oral use • Psychoactive effects slowed to about one hour • Absorption is erratic • High is less intense, but lasts longer than if smoked • IV use • Water insoluble so cannot be injected

40. CANNABIS KINETICS • SMOKING three cannabis joints will cause you to inhale the same amount of toxic chemicals as a whole packet of cigarettes. • The French Consumer Institute tested regular Marlboro cigarettes alongside 280 specially rolled joints of cannabis leaves and resin in an artificial smoking machine. • The tests examined the content of the smoke for tar and carbon monoxide, as well as for the toxic chemicals nicotine, benzene and toluene. • Cannabis smoke contains seven times more tar and carbon monoxide. • Someone smoking a joint of cannabis resin rolled with tobacco will inhale twice the amount of benzene and three times as much toluene as if they were smoking a regular cigarette, the study said.

41. CANNABINOIDS Desired effects of the user • Sense of well being • Relaxation • Euphoria • Modified level of consciousness • Altered perceptions • Intensified sensory experiences • Altered time sense • Sexual disinhibition

42. PHARMACOLOGIC ACTIONS • Psychomotor effects • Behavioral effects • Cognitive effects

43. PHARMACOLOGIC ACTIONS • Psychomotor effects • Object distance distortion • Object outlines distorted • Inability to make rapid judgment • Slowed reaction time • Impaired tracking behavior • Slowed time perception All are dose-related

44. PHARMACOLOGIC ACTIONS Cannabis and Motor Function: fMRI Changes Following 28 Days of Discontinuation • The authors hypothesized that supplementary motor cortex (SMA) and anterior cingulate cortex (ACC) activation in chronic cannabis users, studied 4 to 36 hours after their last episode of use, would disappear by Day 28 of abstinence during finger-tapping tests. • The results suggest that residual diminished brain activation is still observed 28 days after discontinuing cannabis use in motor cortical circuits. Source: Experimental and Clinical Psychopharmacology Volume 16, Issue, Feb. 2008, Pages 22-32.

45. PHARMACOLOGIC ACTIONS • Behavioral effects • “Amotivational Syndrome” • Little scientific evidence for the existence of this • Tolerance to marijuana was supposed to be a manifestation of desensitization of brain cells, and in addition to contributing to the supposed dependence liability this desensitization of brain cells was supposed to create an amotivational syndrome characterized by apathy and inactivity. • The hypothesis was that this desensitization would impede normal brain operations and render individuals somewhat sluggish and unmotivated. The hypothesis has been challenged on both behavioral and pharmacological grounds.

46. PHARMACOLOGIC ACTIONS • Increased focus on taste • Increased appetite (street slang - ”munchies”) • Dry mouth

47. PHARMACOLOGIC ACTIONS • Cognitive effects may be due to a reduction in blood flow to the brain - seen even 30 days after last use in heavy smokers. (A study in February 2005 found increase blood flow – indicative of narrowed arteries; much like those seen in hypertension.) • Impaired short-term memory • Especially verbal IQ • Impaired attention • Impaired integration of complex information • Chronic marijuana user – “College was the best 6 years of my life.”

48. PHARMACOLOGIC ACTIONS • Psychomotor effects • Behavioral effects • Cognitive effects Evidence of brain damage is equivocal in the chronic user

49. PHARMACOLOGIC ACTIONS • British Medical Journal 2006 • 2.9% prevalence of cannabis in the driving population • 2.5% of fatal crashes • 2.7% prevalence of alcohol in a similar population • 28.6% of fatal crashes

50. TEEN USE • University of Maryland’s center for substance abuse research published in Sept 2004 • Warning signs of teen use ( 34,000 6th, 8th, 10th and 12th graders) • Use of cigarettes and alcohol before age 15 • Arrests for alcohol and other drugs • 20 or more unexcused absences from school • Attitude that smoking cigarettes and marijuana is safe