Background History & Prohibition Mechanisms of Action Acute Behavioral & Physiological Effects

1. Background History & Prohibition Mechanisms of Action Acute Behavioral & Physiological Effects Abuse & Effects of Chronic Exposure Medical Use Related Substances Cannabinoids high-resolution scanning micrograph of cannabis

2. Cannabis The term marijuana comes from the Spanish or Portuguese word meaning intoxicant.

3. There is still botanical debate over whether there is 1, 3, or more species of cannabis. Cannabis Sativa Indica is grown for it PSYCHOACTIVE resins. This one may actually be a shorter, bushier version of the plant. Cannabis Sativa Sativa used primarily for its fibers from which hemp rope is made. This species grows as a weed in the US and Canada. Cannabis Ruderalis grows primarily in Russia and not at all in America. Check the species and varieties : http://en.wikipedia.org/wiki/Cannabis_sativa

4. Primary Psychoactive Agent Delta-9 tetrahydrocannabinol (THC) is concentrated in the resin of the plant. Potency depends on the amount of psychoactive substance in the final preparation.

5. Both male and female plants manufacture THC in usable amounts. The resin is secreted in highest quantity by the unfertilized flowers of the female plant grown in the absence of males. The leaves contain 10-20% as much THC as is found in the resin.

6. In cooler more humid climates such as North America less resin is produced but the fiber is stronger and more durable. Uses of hemp fiber are said to include: Chinese paper, the Bible, ropes and sails on Columbus’s boats, the Declaration of Independence, WWII parachutes, and the 1st Levi jeans. In hot, dry climates such as North Africa the fiber content is weak but so much resin is produced that the plant looks as if it is covered with dew.

7. Resin (dew) on leaves

8. Preparations Marijuana:leafy material from cannabis indica that is generally smoked. Contains 2%-5% THC (sativa has <1% THC.) Aka: Grass, pot, weed, bud, Mary Jane, dope, indo (DEA) Sinsemilla (ganja): from the un-pollinated female plant, 4-8% THC. Hashish(charas):a dried concentrate of the resin of cannabis flowers, 8-14% THC. Hashish oil: has 15-60% THC. Marijuana is much less potent. Perhaps 1/3rd to 1/10th as potent as hashish.

9. Bhang: A drink popular in India made of cannabis leaves, milk, sugar and spices, has 2-5% THC. Kief: (Arabic kaifكيف meaning "pleasure, well being”) - is the dried resin glands of cannabis extremely high THC Budder: Processed hashish oil that is reported as being anywhere between 82-100% THC.

10. Cannabinoids Background History & Prohibition Mechanisms of Action Acute Behavioral & Physiological Effects Abuse & Effects of Chronic Exposure Medical Use Related Substances high-resolution scanning micrograph of cannabis

11. An 8000-year time line of cannabis use around the world

12. 2737 BC The earliest reference to cannabis in a Chinese pharmacy book By 1000 BC it had spread to India By 500 BC it was familiar to ancient Greece. Some early references were to the use of cannabis as an inebriant. 430 BC Herodotus reported that the Scynthians burned hemp seeds and inhaled the smoke to induce intoxication.   Social use of the plant spread to the Muslim world and North Africa by 1000 AD. In the 12TH Century Social use of the plant was considered epidemic.

13. A sadhu and his apprentice Use in India dates back to 1000 BC. Bhang is still used during Hindu and Sikh celebrations. Cannabis is seen as a gift from Shiva to aid in sadhana, releasing life from the limitations with which it is bound. A sadhu is an ascetic, who has given up pursuit of the first three Hindu goals of life: kama (pleasure), artha (wealth and power) and dharma (duty). Solely dedicated to achieving moksha (liberation) through meditation and contemplation of God. Consumption of cannabis is a central part of life. Use in Judaism and Christianity is debated by scholars. The herb of interest is most commonly known as kaneh-bos (קְנֵה-בֹשֶׂם) which is mentioned several times in the Old Testament as a bartering material, incense, and an ingredient in holy anointing oil used by the high priest of the temple.

14. Legend has it that an Eastern Mediterranean area had a religious group that committed murder for political reasons. The group was called HASHISHIYYA.  From this word our word “assassin” may have developed. 1299 AD Marco Polo relayed this story in his diary. This group may have given rise to the story of “The Arabian Knights”

15. 1545 Spaniards brought cannabis to the New World. 1611 English settlers brought it to Jamestown, Virginia as a major commercial crop along with tobacco. In the 1700’s George Washington grew cannabis on his farm. Entries in his diary indicated that he maintained a keen interest in cultivating better strains of cannabis, but there is no reason to believe he was interested in anything more than a better quality of rope.

16. 1844, Alexander Dumas refers to the use of hashish in his book The Count of Monte Cristo. “Marco Polo gave them to eat a certain herb, which transported them to paradise, in the midst of ever-blooming shrubs, ever-ripe fruit, and ever-lovely virgins. What these happy persons took for reality was but a dream; but it was a dream so soft, so voluptuous, so enthralling, that they sold themselves body and soul to him who gave it to them…” "Ah, yes, the hashish is beginning its work. Well, unfurl your wings, and fly into superhuman regions.”

17. Napoleon’s soldiers, after a campaign in Northern Africa in the early 1800’s, brought hashish use to France. In the 1840’S, it was popular with French artists to use cannabis at monthly meetings. Allumeuse de Narghilé Lighting the Hookah by Jean-Léon Gérome 1824-1904

18. Documented use since 2000 AD but… Not until 1926 did marijuana appear in the popular press and was associated with the negative elements of the culture. By 1929, 16 states had cannabis listed in their anti-narcotic laws. Mid‑1930’s, Congressional hearings were organized not because marijuana was an inebriant or euphoriant, but because it was consistently associated with crimes of violence (also racial tensions played a role). 36 states regulated the use, sale, and/or possession of marijuana by 1935.

19. By the end of 1936, all 48 states had similar laws. 1936 SCIENTIFIC AMERICAN: “Marijuana produces a wide variety of symptoms in the user, including hilarity, swooning, and sexual excitement. Combined with intoxicants it often makes the smoker vicious with a desire to fight and kill.”

20. U.S. Federal Bureau of Narcotics public service announcement used in the late 1930s and 1940s.

21. 1936 film Marihuana A good girl goes to a party, smokes marijuana, and then goes skinny-dipping with her girl friends. When one of the girls drowns, the dope pushers come up with a plan to hide the body. A turn of events leads up to The girl being pregnant and unmarried. She is forced to give the child up for adoption and become a drug dealer. *Notice the Needles

22. 1936 filmReefer MadnessTragic events follow when high school students are lured by pushers to try marihuana: a hit and run accident, manslaughter, suicide, rape, and descent into madness all ensue.

23. Video collection of 1930’s anti-marijuana movies.

24. 1937 The Marijuana Tax Act was passed. The law did not outlaw cannabis or its preparations, it just taxed the grower, distributor, seller, buyer. But, this was cannabis sativa. The law did not distinguish between the two forms of the plant (sativa was used for hemp rope and not the resins!!). Therefore, it was legal to have cannabis indica in one’s possession. Later states adopted law to make cannabis possession illegal.

25. 1942 The US government asked farmers to plant hemp for use in the war. Hemp for Victory! - USDA Instructional video on how to grow hemp in US

26. 1969 the US Supreme Court declared the Marijuana Tax Act as unconstitutional (in part because of forced self-incrimination). But the Marijuana Tax Act had an amazing effect. Almost immediately, there was a sharp reduction of vicious crimes committed under the influence of marijuana. Why? Also, the price for marijuana increased 6 to 12 times.

27. Gateway Drug Marijuana has more recently been categorized as a Gateway Drug for its role in leading to the use of other illegal drugs. Very few young people use other illegal drugs without first trying marijuana. However, the majority of marijuana users (60%) do not go on to use other illicit drugs. The Terrible Truth (1951)

28. Risk of cocaine use estimated to be >104 times greater for those who have tried marijuana than for those who never have. (DEA) One study showed that rats that had previously been administered THC consumed about 1.5 times more heroin than those that had not. Adolescent cannabis use can overstimulate and alter the pleasure and reward structures of the brain (dopaminergic system), thus increasing the risk of addiction for people who start to use heroin. (Ellgren 2006) Correlational, could be from inherent property of marijuana (ex. brain changes), characteristic of users (ex. risk-seekers), or sociocultural associations with marijuana (ex. peers who use other drugs, lowered inhibitions about drug use).

29. Today Marijuana is a Schedule I substance (most restrictive) under the Controlled Substances Act (1970). Schedule I drugs are classified as having: • a high potential for abuse, • no currently accepted medical use in treatment in the United States • a lack of accepted safety for use of the drug or other substance under medical supervision (Office of National Drug Control Policy)

30. By 1972 the American Medical Association, American Bar Association, and former US Secretary of State George Schultz had proposed liberalization of possession laws. In 1972 the National Commission on Marijuana and Drug Abuse Prevention and Control Act of 1970, encouraged state legislators to consider changes in their regulatory statutes related to marijuana.

31. 1973Oregon became the first state to abolish criminal penalties for marijuana use, substituting civil fines up to $100. This was no different than getting a traffic ticket. By 1978, 9 other states had made possession of a small amount of marijuana only a civil offense. In 1977 President Carter sent a message to Congress in which he asked to abolish all federal criminal penalties for the possession of small amounts of marijuana. He stated: “Penalties against the possession of a drug should not be more damaging to an individual than the use of the drug itself. Therefore, I support legislation amending the federal criminal penalties for the possession of up to 1 ounce of marijuana.”

32. Controlled Substances Act was accompanied by federal sentencing guidelines. In United States v. Booker, a Supreme Court decision from January 2005, the court ruled that the federal sentencing guidelines are advisory and no longer mandatory. This quickly met opposition and debate is in progress. Some conflicts with state laws. Prosecution seems to be at the discretion of the state and the federal governments.

33. Norml.org – a group working to reform marijuana laws

34. Ohio Laws: Conditional release: For first prosecutions. After successfully completing probation, the individual's criminal record does not reflect the charge. Mandatory minimum sentence: When convicted of an offense punishable by a mandatory minimum sentence, must serve the minimum sentence or higher. Not eligible for parole. Decriminalization: The state has decriminalized marijuana to some degree. Typically means no prison time or criminal record for first-time possession of a small amount for personal consumption. The conduct is treated like a minor traffic violation. Drugged driving: This state has a per se drugged driving law enacted. These laws forbid drivers from operating a motor vehicle if they have a certain detectable level of drug or drug metabolite (even if not psychoactive themselves). Texas Laws: Marijuana tax stamps: Mandates that those who possess marijuana are legally required to purchase and affix state-issued stamps onto his or her contraband. Failure to do so may result in a fine and/or criminal sanction.

36. Our Neighbor to the North Ann Arbor, Michigan has enacted some of the most lenient laws on marijuana possession in the country, including: • 1974 voter referendum making possession of small amounts of the substance merely a civil infraction subject to a small fine • 2004 referendum on the use of medical marijuana. However, the far-stricter state laws are still enforced on University of Michigan property, within the city of Ann Arbor.

37. Marijuana is the most commonly used illicit drug. 2005 National Survey on Drug Use and Health estimated the percentage of Americans aged 12 and older that used marijuana: • In their lifetimes (at least once) 97.5 million, 40.1% • In the past year 25.4 million, 10.4% • In the past month 14.6 million, 6.0% (Office of National Drug Control Policy)

38. Use in Columbus, Ohio Marijuana is considered to be extremely available in Columbus. An ounce of low- to mid-range quality marijuana sells for $300-$350, while an ounce of high-quality marijuana sells for $400-$600.25 Office of National Drug Control Policy

39. FBI,Uniform Crime Reports

40. Probability of initiating marijuana use as a function of age Psychopharmacology Fig 13.15 2005

41. Use in Columbus, Ohio Juveniles - Among Franklin County 12th graders surveyed in 2003, 21% reported regular use of marijuana (monthly or more often).

42. Percent of CollegeStudents Using Marijuana in 2004 (Office of National Drug Control Policy)

43. Cannabinoids Background History & Prohibition Mechanisms of Action Acute Behavioral & Physiological Effects Abuse & Effects of Chronic Exposure Medical Use Related Substances high-resolution scanning micrograph of cannabis

44. Classifying Marijuana • Marijuana produces some excitatory effects but it is not generally regarded as a stimulant. • Marijuana produces sedative effects, but a person faces no risk of slipping into a coma or dying. • Marijuana produces mild analgesic effects (pain relief), but it is not related pharmacologically to opiates like drugs. • Marijuana produces hallucinations at high doses, but its structure does not resemble LSD or any other drug formally categorized as hallucinogen.

45. PSYCHOACTIVE PRIMARY AGENT DELTA 9‑TETRAHYDROCANNABINOL(THC)IS CONCENTRATED IN THE RESIN OF THE PLANT.

46. Chemistry was established over 100 years • ago by two chemists, the Smith Brothers. • 50 cannabinoid-based compounds, with • 4 major cannabinoids in the plant: • 2 isomers, a trans-delta-9-THC and a delta-8-THC • A cannabidiol (the 2nd most abundant psychoactive ingredient after THC) • A cannabinol a decomposition product of THC that accumulates as cannabis samples age. • After ingestion, delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active.

47. Endocannabinoidsare the body’s endogenous cannabinoids. Anandamide(Sanskrit ananda inner bliss) is one endocannabinoid. It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body). It is about as potent as THC. Chocolate tree

48. 1500 BC-400 BC - Olmec Indians grew cocoa. 250-900 AD Maya in Central America drank as a beverage flavored with chili pepper, pimento and other spices. Chocolate may derive from xocolatl, the Nahuatl word of the Aztecs of Mexico

49. Chemical structures of the endocannabinoidsanandamide and 2-arachidonylglycerol (2-AG)

50. Time course of plasma THC concentrations THC in a sesame oil suspension