Marijuana product of Cannabis sativa, or the common hemp plant grown abundantly throughout the world cannabis products are distinguished in terms of the content of cannabis resin and, in turn, the concentration of THC, the active psychoactive agent.

Cannabis sativa is selectively propagated for
Fiber e.g. for rope, then usually called hemp
Resin e.g. for drug, then usually called marijuana
Hemp seeds are a common component of birdseed, but they are unsuitable for growing resinous marijuana, and they are treated so they will not germinate.

The History of Marijuana and
Hashish
The earliest records of marijuana come from
Chinese writings nearly five thousand years ago; the use of hashish originated in North Africa and Persia in the ninth or tenth century A.D.
In the United States, marijuana was available in patent medicines during the late 1800s, but its popularity did not become extensive until the
1920s.

The History of Marijuana and
Hashish
1910-1950s marijuana use tied to black jazz music (New Orleans)
(no, NBA fans, Utah is not the birthplace of jazz, and no Mormon priest or politician was involved)
(e.g. Louis Armstrong busted in 1931) and later to swing music
1930s
Federal and state regulation begins
1938 scare film, Reefer Madness

The History of Marijuana and
Hashish
1940s – 1950s penalties for possessing and selling marijuana escalate use among musicians in the spreads to the “beat” community of the 1950s
1960s marijuana a major player on college campuses and young people in general birth of legalization movements remains associated with music
(e.g. Bob Dylan introduces the Beatles to marijuana in a N.Y. hotel room)

The History of Marijuana and
Hashish
1970s marijuana use becomes mainstream, particularly among the young law enforcement becomes more relaxed major dealers, major money becomes the focus

Acute Effects of Marijuana
onset of effects are rapid elimination is slow absorbed into fatty tissue released slowly may take days or weeks for THC to be completely eliminated

Acute Effects of Marijuana physiological effects cardiac acceleration reddening of the eyes ptosis of eyelids

Acute Effects of Marijuana psychological effects euphoria giddiness perceptual slowing of time reduced attention/concentration memory deficits increased hunger
Marijuana binds to specific THC (cannibinoid) receptors in the brain endogenous neurotransmitter is anandamide

Where in the brain does marijuana exert its effects?
Cannabinoid receptors are widespread in the brain cortex limbic system (hippocampus amygdala) basal ganglia (including nucleus accumbens) cerebellum emetic (vomiting) circuits of the brainstem receptors are sparse in thalamus pons remainder of the brainstem

Chronic Effects of Marijuana tolerance develops no physical dependence when doses are moderate a mild psychological dependence

Chronic Effects of Marijuana
Carcinogenic effects are suspected marijuana smoke contains many of the same harmful components as tobacco smoke inhalation is deeper and more prolonged
However, no clinical data currently exist to support this suspicion

Table 7.1

True (A) or False (B) impairs the immune system increases the risk of lung cancer significantly impairs driving ability increases the likelihood of birth defects

The Amotivational Syndrome and the Gateway Hypothesis
The “amotivational syndrome,” characterized by general apathy and an indifference to long-range planning, as a result of chronic marijuana use has been largely discredited.

Figure 7.1

The Amotivational Syndrome and the Gateway Hypothesis
An alternative explanation for the behavioral changes is that chronic marijuana users are involved in a deviant subculture that tends to undermine traditional values of school achievement and longterm aspirations.
Do you agree that marijuana users are generally part of a deviant subculture?
(A=Yes, B=No)

The Amotivational Syndrome and the Gateway Hypothesis chronic marijuana use as a “gateway” to other drugs users of other drugs previously smoked pot marijuana inherently sets the stage for future patterns of drug abuse
By what mechanisms could this happen?
(biological, social, cultural)
What is the evidence for and against the gateway hypothesis in the context of the use of marijuana and
1. its pharmacological effects
2. its socio-cultural effects
3. its predisposition to drug abuse

The Amotivational Syndrome and the Gateway Hypothesis use of alcohol and cigarettes precedes marijuana use and that marijuana use precedes the use of other illicit drugs is this a necessary condition to establish marijuana as a gateway drug?
is it sufficient?
marijuana use and the subsequent use of other illicit drugs are statistically correlated is this necessary for the gateway hypothesis?
is it sufficient?

Addiction Liability little evidence that marijuana exposure itself leads to physical or psychological dependence on other drugs.
only 9% of those who ever used become dependent
(dependence is associated with gradual increase in use) no scientific evidence that it is a “gateway” drug

Addiction Liability
Withdrawal symptoms difficult to demonstrate
10 hour onset and 5 day duration
Anxiety
Mental clouding
Insomnia
Anorexia
Irritability
Tremor
Depression
Headache
Craving
Very similar to nicotine withdrawal, except weight loss in marijuana weight gain in nicotine withdrawal

Addiction Liability
Withdrawal symptoms may be due to the release of corticotropin releasing factor (CRF) in the amygdala (stress response)
Similar to the CRF release in opiate, alcohol and cocaine withdrawal
71% of marijuana users relapse to marijuana use within
6 months after achieving initial 2 weeks of abstinence

Patterns of Marijuana Smoking
The current prevalence rate of marijuana smoking among adolescents and young adults is lower than in the late 1970s.
However, in 2009, 33 percent of high school seniors reported smoking marijuana in the past year.
Of concern is the considerably greater potency of marijuana that is now available and the continuing potential risk of marijuana adulteration.

Figure
7.2
Use of illicit drugs, users age 12 and older (2009)

Patterns of Marijuana Smoking
Percentage of Young People Using
Marijuana in the Past Year, by Age
Group (2001)
35%
30%
25%
20%
15%
10%
5%
0%
(this pattern of use is not what one would expect if dependence was common)
12--13 14--15 16--17 18--20 21--25
Marijuana use is limited in early teens (2% at age 12) increases in prevalence throughout teens begins to decline after age 20 less than 1% of those over age 60 use marijuana
What might account for this lifetime pattern of use?

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

is likely to reduce academic performance if used regularly will cause the smoker to experiment with cocaine or heroin in the future in adolescence will generally be preceded by experimentation with tobacco or alcohol.

Medical Marijuana,
Decriminalization and Legalization useful in the treatment of glaucoma and asthma most effectively used to treat nausea and weight loss mid-2010 fourteen U.S. states had approved medical marijuana

Medical Marijuana,
Decriminalization and Legalization
2009
U.S. Department of Justice federal prosecution those using marijuana in a medical setting in compliance with states’ laws is not a priority
However, marijuana is still classified classified as a controlled substance without medical use.

Medical Marijuana,
Decriminalization and Legalization
Medical use of marijuana is no longer prosecuted by the federal government but that use is not recognized by the FDA.
This means that marijuana is now a:
A. Schedule I substance
B. Schedule II substance
C. Schedule III substance
D. Schedule IV substance
E. Schedule V substance

Medical Marijuana,
Decriminalization and Legalization
Federal policy in the United States toward marijuana smoking has evolved to the point of essentially decriminalizing the possession of marijuana in small amounts.
Legalization is still highly controversial, although public support has gradually increased in recent years.

What is the difference between legalization and decriminalization?
In general, should marijuana be
A. legalized
B. decriminalized
C. remain illegal (status quo)
What about medical marijuana?

Medical Uses
Relieve nausea
Most trials used dronabinol (synthetic Δ-9 THC) and not smoked marijuana; however, in trials that compared the two, dronabinol was more effective.

Medical Uses
The U.S. Food and Drug Administration (FDA) has approved Valeant Pharmaceuticals International to bring the synthetic cannabinoid drug nabilone (synthetic cannabidiol; Cesamet) back to market after 17 years.
Nabilone is also sold in Canada.
The drug, similar to the THC medication, Marinol
(dronabinol), was originally marketed by Eli Lilly and Co. but withdrawn from the market in 1989. It is now approved by the FDA for treatment of vomiting and nausea caused by chemotherapy and is listed as a
Schedule II controlled substance.

Medical Uses
Increase appetite
Dronabinol (prescription THC) does appear to work
No controlled studies in smoked marijuana
Smoked and oral form increased weight (fat not lean body mass)
Annals 2003;139:258-266
Decrease muscle spasm
Suggested for multiple sclerosis
Anecdotal information
Decrease intraocular (eye) pressure
Better preparations available for the control of intraocular pressure as seen in glaucoma

Medical Uses
Control of chronic pain
NIDA study at University of Arizona
Compound am1241
Acts on CB2 receptors
Pain relief without the central nervous system side effects such as sleepiness and anxiety
Study done on neuropathic pain suggested that stimulation of CB1 receptors in the spinal cord blocks pain, and that cannabinoids may also act directly on nociceptors

Medical Uses
Sativex
Whole plant medicinal cannabis extract (Δ-9 THC)
Produced by Bayer and GW pharmaceuticals and approved for use in Canada for multiple sclerosis and neuropathic pain (2005)—as adjunct to maxed-out opiates
Phase 3 trials in multiple sclerosis patients showed that sublingual spray was safe and effective for symptom relief

Medical Uses
2004 - Israeli soldiers suffering from combat stress were treated with cannabis to relieve symptoms
PTSD trials are ongoing
THC may silence genes that code for vascular endothelial growth factor (VEGF)
VEGF stimulates the growth of blood vessels in tumors

Medical Uses
Marijuana may have a benefit in treating bipolar disorder
Cannabidiol (a cannabinoid found in cannabis) has a calming effect but does not produce a “high”
THC prevents severe highs and lows
C.H. Ashton, P. Gallagher, P.B. Moore, and A.H. Young (2005 )
Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential , Journal of Psychopharmacology, 19 , 293-300.

Medical Uses
THC is more effective at blocking an enzyme that causes the brain damage common to Alzheimer's disease than approved drugs already on the market low doses of THC inhibit AChE (breaks down acetylcholine), may thus improve learning and memory.
The drug also appears to prevent the formation of neurofibrillary tangles
Eubanks, L.M., et al. (2006) A Molecular Link between the
Active Component of Marijuana and Alzheimer's Disease
Pathology, Molecular Pharmaceutics, 3 , 773-777 .

Medical Uses inflammatory bowel disease (IBD) cannibinoid reduce intestinal motility and secretions cannibinoids reduce inflammation
CB1 knockouts or CB1 blockade enhances inflammation
CB1 receptors may be clinically useful to promote healing of the lining of the gut in ulcerative colitis and
Chrohn’s disease

Medical Uses
Overall problems of use
Mode of administration
No smoking in hospitals
No standard dose of smoked marijuana
Smoke is hazardous in and of itself
Smoking may impair immune system response
Difficulty concentrating on complex tasks
Slowed reaction times
Tolerance develops quickly
Effect is 4 - 6 hrs

Medical Uses
Overall problems of use
Chronic bronchitis can develop
Pharyngitis (inflammation of the pharynx) can develop
Large airway obstruction can be seen
Acute panic reactions, paranoid reactions possible
Acute paranoia can develop
Heart rate increases 20 - 100% for 2 - 3 hrs
Decreased blood pressure seen with use

Medical Uses
Is there any reason to legalize marijuana if drugs acting on cannabinoid receptors can be developed that are effective treatments but do not have abuse potential?