1. Cannabinoids 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.
mq-fig jpg

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 :

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
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 kaif كيف 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 % THC.
Notice all of these preparations include heating. May activate it.
I cannot find kief or budder in any book or scientific article, only on webpages, do they really exist?

10. Cannabinoids History & Prohibition Background Mechanisms of Action
Acute Behavioral & Physiological Effects
Abuse & Effects of Chronic Exposure
Medical Use
Related Substances
mq-chopener-13.jpg
high-resolution scanning micrograph of cannabis

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

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 and his apprentice
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.
The first bible may have been printed on hemp paper.
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

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 film Reefer Madness Tragic 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.
mq-fig jpg

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

24. 1937 The Marijuana Tax Act was passed
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. Also, the price for marijuana increased 6 to 12 times.
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.
Marijuana used by 75% of illicit drug users, 60% of illicit drug users only use marijuana
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).
What if all drugs were legal? Or one in particular, let’s say… cocaine.
What do you guys think?
At one time cocaine was legal. It was used by Coca-cola. Some of your great-grandma’s probably used it. It was also used for teething babies. It was a common pain relief medication.
But it wasn’t that popular.
Marijuana use became popular when alcohol was prohibited, but subsided when alcohol became legal again maybe some aspects of drug use really are just characteristics of the users.

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)
Schedule 2 – addictive potential, some medical use
To put it in perspective, cocaine and morphine are both schedule 2, although they can be lethal, side effects are worse, more addictive…
Valium is schedule IV
Caffeine and nicotine are not scheduled

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. 1973 Oregon 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
More users? More arrests? More aggressive law enforcement?
Cannabis is less likely than alcohol to precipitate aggressive behavior, it is more likely to lead to lethargy.
FBI, Uniform Crime Reports

40. Probability of initiating marijuana use as a function of age
mq-fig jpg
Psychopharmacology Fig

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 College Students Using Marijuana in 2004
(Office of National Drug Control Policy)
Past Month
18.9%
Past Year
33.3%
Lifetime
49.1%

43. Cannabinoids Mechanisms of Action Background History & Prohibition
Acute Behavioral & Physiological Effects
Abuse & Effects of Chronic Exposure
Medical Use
Related Substances
mq-chopener-13.jpg
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.
The carbon rings make it liquid soluble.

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. Endocannabinoids are 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.
Anandamide is an arachodonic acid derivative.
Endocannabinoids are fatty acide from dietary fat. Later in the talk I will discuss a drug that can reduce fat intake.
Chocolate tree

48. 1500 BC-400 BC - Olmec Indians grew cocoa
1500 BC-400 BC - Olmec Indians grew cocoa 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 endocannabinoids anandamide and 2-arachidonylglycerol (2-AG)
mq-fig jpg Very lipid soluble. Lot’s of carbon rings (bends are carbons).

50. Time course of plasma THC concentrations
THC in a sesame oil suspension
mq-fig jpg
Plasma conc by time. Identify axis.

51. Time course of plasma THC concentrations
mq-fig jpg

52. Most THC is absorbed from the blood within 30 min.
After a 6 min smoking period, peak blood levels reached at about 7 min (100 ng/ml plasma).
Most THC is absorbed from the blood within 30 min.
Moves rapidly into the brain and across the blood/brain/placental barrier. Because fatty chains make it very lipid soluble.
Half-life is about 19 hours. Can store in fat cells.
Established physiological effects are dose related.
Lethal dose for THC use has now been studied, and no human deaths have been reported due to intoxication from cannabis.
Lethal dose would be about 1000 x the dose needed for intoxication and used for recreation

53. 2/3 of metabolites are excreted in feces.
Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use.
Primary metabolite has a half-life of 50 hours. The complete elimination of the drug can take as long as 6 weeks!
After ingestion, delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active.
2/3 of metabolites are excreted in feces.
1/3 of metabolites are excreted in urine.
Bile = lipid soluble. Most drugs are excreted in the urine.
Urine inactivates metabolites because of it’s acidity. So, in this case, drinking the urine of a user wouldn’t work.

54. Location of endocannabinoid receptors in a rat brain
CB1 receptors (red) are widely distributed in the brain. K. MACKIE/UNIV WASHINGTON, Science, 2006

55. Unlike classical neurotransmitters…
Endocannabinoids are not stored in vesicles.
Endocannabinoids are retrograde transmitters. They are released from the postsynaptic cell and act on the presynaptic cell.
Not stored = made and released immediately.

56. May act pre-synaptically to reduce the release of glutamate and GABA
mq-fig jpg

57. Unlike classical neurotransmitters…
Endocannabinoids are not stored in vesicles.
Endocannabinoids are retrograde transmitters. They are released from the postsynaptic cell and act on the presynaptic cell.
Reduces the amount of presynaptic neurotransmitter released.

58. May act pre-synaptically to reduce the release of glutamate and GABA
mq-fig jpg

59. This permits the postsynaptic cell to control its own incoming synaptic traffic. Effect depends on the nature of the presynaptic transmitter that is being controlled. THC can inhibit presynaptic release of GABA & Glu.

60. Cannabinoids Acute Behavioral & Physiological Effects Background
History & Prohibition
Mechanisms of Action
Acute Behavioral & Physiological Effects
Abuse & Effects of Chronic Exposure
Medical Use
Related Substances
mq-chopener-13.jpg
high-resolution scanning micrograph of cannabis

61. Paucity of Data
Cannabis has been difficult to study because of prohibition and because it is commonly used by people who also use alcohol or other drugs which are confounds to a study.
Considerable biases in the scientific data exist on the adverse effects of marijuana.
A former president of the AMA actually fabricated data critical of marijuana use!
Confounding variables.

62. Dose Response Effects
Threshold doses of 2 mg smoked, 5 mg orally, produce euphoria.
7 mg smoked, 17 mg orally, produces feeling enhanced perception and change in sense of time passage.
15 mg smoked, 25 mg orally, subjects report marked changes in body image, perceptual distortion, delusions, and hallucinations.
Oral intake associated with nausea, physical discomfort and hangover because dose level cannot be titrated as accurately as smoking.

63. Stages of marijuana intoxication include:
The buzz, the high, being stoned, and the come-down
Initial effects are somewhat stimulating and in some individuals may elicit mild tension or anxiety.
Second phase replaces this with a pleasant feeling of well-being.
Later phases are reported to make the user introspective and tranquil. Rapid Mood changes often occur. Periods of enormous hilarity may alternate with contemplative silence.  
Other reported effects include: suspiciousness and paranoia, depersonalization, sense of loss of control, dysphoric reactions, increased sensory awareness (tested, but not supported)

64. Step 2: the user has to learn to identify and control the effects.
Generally, a new user has to learn how to smoke marijuana. There are three stages:
Step 1: involves deeply inhaling the smoke (breath-holding does not substantially enhance the effects of marijuana smoking – lipid solubility). 
Step 2: the user has to learn to identify and control the effects.
Step 3: the user has to learn the label the effects as pleasant.
Some peopl ( ex. old people with cancer) tend to have trouble with step 3.

65. Because of this learning process, usually first time users do not achieve the euphoric stoned or high condition of the repeat user.
Also because smokers learn to enjoy marijuana: In a study comparing effects of placebos and cigarettes containing 9 mg of THC, experienced users reported moderate levels of intoxication after use of placebo cigarettes. So, save your money!
associations

66. Physiological Changes
Tachycardia (increased heart rate)
Enlarged pupils (in some users)
Dryness of mouth and throat
Reddening of the eyes
Inconsistent blood pressure changes
First 2 are anti-muscarinic, along with attentional deficits (like scopalamine)
Last 3 are all prostaglandin related. Aspirin (a COX-2 inhibitor and therefore inhibitor of prostaglandin synthesis) can block them all.

67. Eating Changes (the Munchies)
The presence of the cannabinoid receptor in the ventromedial hypothalamus may explain the munchies.
There is also a drug, Remonobant, that does the opposite and can be a therapy for over-eating. I will discuss this drug later…

68. Hunger may be effected by TCH concentration, as cultural differences are observed (Jamaicans think of it as appetite suppressant).
In a study, 9 male subjects were given THC-containing cigarettes either (1) before a private work period, or (2) during access to social periods with other subjects. (1) did not lead to increased food intake (2) did lead to increased food intake, especially between meals.

69. Sexual Functioning
In North America, marijuana is thought of as a sexual enhancer, in India it is considered a sexual depressant.
Low doses enhance sexual desire in males, while high doses tend to suppress it, even to the point of impotence.
(Levinthal 2006).

70. Psychomotor Performance
Can also impair psychomotor performance, especially in demanding tasks such as driving.
Psychomotor effects could be due to the large amount of cannabinoid receptors found in the basal ganglia and the cerebellum, both related to movement.

71. Psychomotor Performance
Marijuana smokers are more likely to get into an auto accident. Reaction time is the same, but slower at noticing things that should be stopped for.
Decline in sensory-motor performance as well as attention and memory will persist well after the point at which the marijuana smoker no longer feels high.

72. Effect on Memory
One consistent alteration in function is on short-term memory.
The encoding and consolidation of short-term to long-term memory is impaired with marijuana intoxication.
Researchers have concluded that information retrieval is intact and not altered by marijuana intoxication.
The effects on memory are different from those seen with alcohol.
In some ways, like anti-muscarinic effects (ex. scopalamine)

73. Oral THC produces a dose-dependent impairment in explicit memory
mq-fig jpg

74. Effects of Marijuana on the Brain
The hippocampus is a part of the brain’s limbic system necessary for learning and memory. The prefrontal cortex is involved in information processing and higher processes.
CB1 Receptors in Hippocampus
Hippocampus and prefrontal cortex both rich in CB1 receptors.
Also, if it decreases glutamate release, this could affect cognition and learning (LTP)

75. Cannabinoids Abuse & Effects of Chronic Exposure Background
History & Prohibition
Mechanisms of Action
Acute Behavioral & Physiological Effects
Abuse & Effects of Chronic Exposure
Medical Use
Related Substances
mq-chopener-13.jpg
high-resolution scanning micrograph of cannabis

76. Addiction can occur to THC, but only at dose and use levels far above what is now used recreationally.
1977 Report stated that moderate marijuana smoking does not cause changes in the physical structure of the brain, at least those that can be detected. (Does not kill cells – no “dormancy”)
Sensitization develops with prolonged use at recreational levels i.e. less drug being necessary with each succeeding use.
This is related to its high lipid solubility. Desensitization occurs, but as more THC accumulates in the body, less is needed to reach the threshold of effect.
THC is lipid soluble, so it stores in the fat cells. If the fat cells are “filled” by chronic use, then new intake would send THC up it’s concentration gradient – more goes directly to blood and brain, doesn’t get sucked into fat.

77. Desensitization of cannabinoid receptors produced by chronic THC exposure
3 Days THC
7 Days THC
0 Days THC (Control)
Looking down from the top of the brain…
Changes in Cannabinoid receptors as shown by this specific marker.
We don’t know exactly what this means.
14 Days THC
21 Days THC
Psychopharmacology, 2005

78. Time course of overall withdrawal discomfort in heavy marijuana users
IRRITABILITY, VOMITING, NAUSEA, DIARRHEA, SLEEP DISTURBANCES
mq-fig jpg

79. Medical Concerns Lungs & Heart Immune system Reproduction Cognition
Usually no obvious high frequency physiological effects of moderate use of marijuana over a 5-10 year period. But, in comparison, there are no obvious high frequency serious effects of moderate use of cigarettes over a 5-10 year period either.
Concern usually arises when use is more frequent that 2 or 3 uses per week.
Lungs & Heart
Immune system
Reproduction
Cognition
Psychological effects
Amotivational Syndrome
This is one of the 6 things I will talk about…

80. Effects on the Lungs & Heart
Throat and respiratory disorders and impaired lung functioning are common among chronic marijuana smokers.
Similar respiratory problems that tobacco smokers have, including: daily cough and phlegm, symptoms of chronic bronchitis, and more frequent chest colds. (At first passageways widen, but after chronic exposure, they constrict).

81. Effects on the Lungs & Heart
Marijuana and tobacco produce the same irritants and carcinogens. Marijuana has higher concentrations of some carcinogens. Regardless of the THC content, the amount of tar inhaled and carbon monoxide absorbed are 3-5 times greater than tobacco smokers. May be due to inhaling more deeply and breath-holding. (Possibly ingest less irritants in vapor, ex. hookah).
Evidence that marijuana smoking increases risk for head, lung, and respiratory tract cancers.

82. Effects on the Lungs & Heart
Marijuana smoking increases heart rate and temporarily weakens heart muscle contractions. It is dangerous for patients with heart disease. One study has indicated that an abuser's risk of heart attack more than quadruples in the first hour after smoking marijuana (Mittleman, 2001).
Marijuana was once felt to be helpful to patients suffering from angina (chest pain due to lack of blood and oxygen). This is not true, because it reduces delivery of oxygen to the heart and speeds the heart until onset of angina pain.

83. Effects on Immune System?
Two types of receptors are known. CB1 is in the brain and CB2 are on immune cells.
Most research concludes that it does suppress some aspects of the immune system. But this is subtle.
It’s evolutionarily ancient

84. Effects on Reproduction
There is not evidence of long term reproductive problems from cannabis use, yet hormonal changes do occur.
Males:
Reduces level of testosterone (still within normal levels)
Reduces sperm count (10 joints/day, effect disappears when use stopped)
Changes in shape and morphology of sperm
Effects of THC can be estrogen-like producing breast development (gynecomastia).
Females:
Reduction in luteinizing hormone, necessary for egg implantation into the uterus. (Not seen in regular users – implies tolerance).
Reduction of prolactin levels (associated with increased release of dopamine in the hypothalamus), effecting lactation

85. Effects on Cognition
There is evidence that long term use may lead to deficits in learning memory and attention.
However, it is unknown how long these deficits may persist after abstinence from the drug.

86. Effects of Heavy Marijuana Use on Attention, Learning, & Memory in Undergraduates
Researchers compared 65 "heavy users," (smoked a median of 29 of the past 30 days), and 64 "light users," (smoked a median of 1 of the past 30 days).
After hours of abstinence from marijuana and other illicit drugs and alcohol, the undergraduates were given several standard tests measuring aspects of attention, memory, and learning.
Heavy marijuana users made more errors and had more difficulty sustaining attention, shifting attention to meet the demands of changes in the environment, and in registering, processing, and using information.
However, the question remains open as to whether this impairment is due to a residue of drug in the brain, a withdrawal effect from the drug, or a frank neurotoxic effect of the drug.
H. G. Pope Jr and D. Yurgelun-Todd, 1996

87. Significant prior usage may reduce the adverse cognitive effects of acute marijuana exposure.
This has led to the hypothesis that behavioral (“cognitive”) tolerance develops in heavy marijuana smokers (Hart, 2001).

88. Does marijuana lead to ? Psychosis
There is evidence that cannabis use is correlated with degradation in mental health, especially in those with a predisposition to mental illness. However, it is uncertain whether cannabis use is a cause, contributing factor, associated social phenomenon, or type of self-medication. (Henquet, 2004)
In North Africa and India, higher incidence of psychiatric problems associated with THC are reported. The THC is usually more concentrated, used more frequently, and exposure over a lifetime is generally greater than the US.

89. The DSM-IV has a classification called 'cannabis psychosis' which is very rare. In susceptible individuals, ingestion of sufficient quantities of the drug can trigger an acute psychotic event.
Pharmacology books stated that people who had a history of repeated frustrations, and deprivations, who were sexually maladjusted, especially homosexuals, or those who seek escape and sometimes possess major personality defects and are often psychopathic, are the kinds of people who smoke marijuana.
1971, Reported that “Moderate to heavy use of marijuana in adolescents and young people without predisposition to psychotic illness may lead to ego decomposition, ranging from mild ego disturbance to psychosis.” (Kolansky and Moore)
They concluded that marijuana smoking leads to psychosis.

90. Reefer Madness (1936) - A man becomes completely insane after heavily using marijuana.

91. The psychosis theory was tested by Altman and Evenson:
They administered questionnaires to people who were being admitted to mental institutions in Missouri.
They did this until they identified 38 individuals who had used marijuana prior to having shown psychiatric symptoms.
Found out what else these patients were doing prior to being admitted, and discovered 10 other events that occurred more often than marijuana use….
Psychosis studies were poor because they set out to prove that there was a cause and effect relationship between marijuana and psychosis, when it was just a correlation.
Psychotics who used marijuana could have been using other drugs as well, we don’t know what they asked.
Some people questioned their findings. They showed that many more things correlate with psychosis.

92. 1. Watching late night television!!
These included the following (in order of frequency):
10. Growing long hair
9. Masturbation
8. Driving a car
7. Taking a sex education class
6. Having sexual intercourse
5. Beer drinking
4. Dancing
3. Tobacco use
2. Kissing
And the most frequent thing they did that may have correlated best with psychosis…
1. Watching late night television!!

93. Amotivational Syndrome.
Recent studies have found that users of moderate amounts of marijuana show no personality disturbances, but heavy users were characterized as suffering from apathy, dullness, lethargy, and impairment of judgment.
However, heavy users were defined as people who smoked marijuana cigarettes per day! (1 joint ever waking 5 mins!)
This is also correlational evidence.
Use is inversely correlated with educational performance. Associated with decrease in grades, more negative attitudes toward school, and increased absenteeism.

94. Cannabinoids Medical Use Background History & Prohibition
Mechanisms of Action
Acute Behavioral & Physiological Effects
Abuse & Effects of Chronic Exposure
Medical Use
Related Substances
mq-chopener-13.jpg
high-resolution scanning micrograph of cannabis

95. Medical Uses of Cannabis
It was never considered as a medical remedy for any ill, so has few references in medical history but…
2737 BC The earliest reference to cannabis was in a pharmacology book. Assessed by Chinese emperor Shen Nung ("the Divine Farmer" )
He referred to it as the liberator of sin. He recommended it for the following: female weakness, gout, rheumatism, malaria, beri beri, constipation and absent mindedness.
At this time they probably also used it as a laxative by eating it.
Shen-nung pen ts'ao pei yao i fang ho pien (Herbal and Prescriptions)

96. 200 AD Chinese physician Hoa-Tho recommended
the resin mixed with wine as a surgical anesthetic.
Not mentioned in European medicine until 1800’s.
1839 Cannabis preparations were found to be
nontoxic and used clinically as an effective anticonvulsant and muscle
relaxant. Also used for the relief of pain associated with rheumatism.
1860 The Ohio State Medical Society Committee (McMeens, 1860:1) noted the success of cannabis in the treatment of neuralgic pain, nervous rheumatism, appetite stimulation, stomach pain, gonorrhea, dysmenhorea, uterine hemorrhage, tedious labor (delivery), infantile convulsions, hysteria, mania, delirium tremens, palsy, muscular spasms, epilepsy, tetanus, bronchitis, and asthma (On an acute basis, increases the diameter of air passage in lungs and could be useful for asthma).
Actually could help asthma because it opens up the bronchioles.

97. 1949 A report fount cannabis to be effective in some cases when Phenytoin (Dilantin), anti-convulsant of choice, was found to be ineffective.
Queen Victoria and Sir William Osler found it to be effective in the treatment of headaches and migraines.
1972 Report demonstrated that marijuana smoking reduces fluid pressure inside the eye, and was effective in treatment of glaucoma. (1975 1st legal use)
Cannabis has some bacteriocidal characteristics and may be effective against gonorrhea.
Won’t work for glaucoma long-term because respiratory damage and risk of cancer from long-term daily smoking.
1975 Medications containing pure THC were found to be effective in reducing severe nausea caused by anti-cancer drugs.

98. Current Medical Use of Cannabinoids
Cannabinoids have found medical use in the treatment of nausea and vomiting in chemotherapy patients and as an appetite stimulant in AIDS patients.
They’ve been shown to attenuate the pathogenesis of multiple sclerosis.
Cannabinoids also have potential in the treatment of degenerative diseases such as Parkinson’s Disease and Alzheimer’s by turning off overactive immune cells.
Won’t work for MS long-term because respiratory damage and risk of cancer from long-term daily smoking.
Problem for AIDS treatment is that raw marijuana contains bacteria and fungi, which are very bad for immunocompromised people. For AIDS, synthetic treatments are more likely to be used.
Hempfest 2004 Seattle, Washington (AFP/Getty Images/Ron Wurzer)

99. Cannabinoids in Neuroprotection
Cannabinoids are both neuroprotective and anti-inflammatory due to their ability to stimulate the production endogenous cytokine receptor antagonists (turn down immune system).
THC and cannabidiol (a non-psychoactive cannabinoid), both reduced glutamate induced excitotoxicity. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a cannabinoid receptor-independent mechanism of action. It was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants.
Hampson AJ, Grimaldi M, Lolic M, Wink D, Rosenthal R, Axelrod J. 2001

100. Cannabinoid Neuroprotection Against Excitotoxicity
Cannabinoid Receptor Activation
Glu (excitatory)
Excitotoxicity
Saved Cell
Decreased Release
Cell

101. Cannabinoid influence on cell survival/death
Cannabinoids may induce proliferation, growth arrest, or apoptosis (death) in a number of cells, including neurons, lymphocytes (immune cells), and various transformed cells. The variation in drug effects may depend on drug concentration, timing of drug delivery, and type of cell examined.
Most of the experimental evidence indicates that cannabinoids protect neurons from toxic insults such as glutamatergic overstimulation, ischemia, traumatic insult and oxidative damage.
Guzman M Sanchez C & Galve-Roperh I 2001

102. In contrast, cannabinoids induce apoptosis of glioma cells in culture and regression of malignant gliomas in vivo. Breast and prostate cancer cells are also sensitive to cannabinoid-induced antiproliferation.
Regarding the immune system, low doses of cannabinoids may enhance cell proliferation, whereas high doses of cannabinoids usually induce growth arrest or apoptosis.
The neuroprotective effect of cannabinoids may have potential clinical relevance for the treatment of neurodegenerative disorders such as multiple sclerosis, Parkinson's disease, and ischemia/stroke, whereas their growth-inhibiting action on transformed cells might be useful for the management of malignant brain tumors.
Guzman M Sanchez C & Galve-Roperh I 2001

103. In the future Cannabinoids may be further explored for usefulness in:
Pain (via its actions in the periventricular hypothalamus), anxiety, insomnia, cough, excessive menstrual bleeding, withdrawal from narcotics and alcohol, poor appetite, epilepsy, migraines, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease.
Synthetic cannabinoids have been created, including dexanabinol which is a noncompetitive antagonist of NMDA glutamate receptors and potent anti-oxidant, but does not bind to CB1 receptors, so it does not produce associated euphoria.

104. Prohibition
Doctors may not "prescribe" marijuana for medical use under federal law, though they can "recommend" its use under the First Amendment.

105. CannabisFacts.ca - Canadian Org

106. The Anti-Cannabinoid
Rimonabant

107. Cannabis is a substance shrouded in political conflict.
Cannabis has some harmful effects and some medical uses.
Depending upon one’s inclination it would be possible to present either a strongly anti-cannabis or a strongly pro-cannabis position with the data that presently exists in the literature.
Just to summarize before I go on to the rest of the talk…

108. Cannabinoids Related Substances Background History & Prohibition
Mechanisms of Action
Acute Behavioral & Physiological Effects
Abuse & Effects of Chronic Exposure
Medical Use
Related Substances
mq-chopener-13.jpg
high-resolution scanning micrograph of cannabis

109. Terpenes
Marijuana, catnip, wormwood, mints are all in the family of terpenes.
Terpenes can all be broken down into isopentane groups
Thujone (wormwood)
Delta-9-THC

110. Various uses of Catnip tea for medicinal purposes: curing chronic bronchitis, diarrhea, upset stomach, infant colic, flatulency, spasms, and “various lower type female disorders”.
The tea is said to induce perspiration and has been used to break fevers, bring on sleep, and to cool a person down on a hot summer day.
Catnip’s active ingredient, nepetalactone causes mood elevation and sedation in humans and euphoria in cats.

111. Wormwood
Bitter taste (due to absinthin). Has a taste threshold of one part in
The nurse in Romeo and Juliet smeared oil of wormwood on her nipples to wean Juliet.
In the 1850’s it was noticed that prolonged consumption was associated with addiction, euphoria, auditory and visual hallucinations and hyperexcitability.
Chronic use is associated with contractions of the face muscles and extremities, anxiety, paranoia, energy loss, numbness, headaches, delirium, paralysis and death.
Thujone produces convulsions and death at high doses.

112. Wormwood (artemisia absinthium) was used in US and Europe as a sedative.
Oil of wormwood was the most active ingredient in the bright green (due to chlorophyll) alcoholic hallucinogenic drink called absinthe. The oil contains thujone.
Thujone is described as a GABA receptor antagonist. It was thought to activate CB receptors because of similarity in structure and behavioral effects as THC, but this has come into dispute.
1896 poster

113. Mixed with wine, the herb has been used since antiquity, and was very popular with European artists. VanGogh was particularly addicted.
The ritual was to pour the emerald-green liquid slowly over sugar held in a perforated spoon and then diluted with water.

114. Thujone is found in low amounts in drinks such as Vermouth (from the German wermuth for wormwood), Chartreuse, and Benedictine.
In 1971 Henri-Louis Pernod bought the formula to make absinthe under his trademark. Then in 1915, his family was forced by the French government to remove wormwood from its drink. The new product is called Pernod.
In 1868, the American Journal of Pharmacology wrote “It’s an ignoble poison, destroying life not until it has more or less brutalized its votaries, and made driveling idiots of them.”

115. The End Cab Calloway – Reefer Man (1933)
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Cab Calloway – Reefer Man (1933)
Questions to Holly

116. Links Office of National Drug Control Policy
blog at
Research
Columbus Ohio Demographics
Deliniated Ohio Laws
Video History of Cannabis
Cab Calloway - The Reefer Man – 1933
Your Brain on Drugs 1980’s Commercial
Hemp for Victory – US pro-hemp propaganda during WWII
The Terrible Truth (1951) – Gateway Drug