1. Marijuana
Marijuana is a mixture of dried and crumbled leaves, small stems, and flowering tops from cannabis sativa, cannabis indica, cannabis ruderalis.
It can be consumed orally, as in cookies or brownies, but is usually smoked in rolled cigarettes known as “joints,” various kinds of pipes, or in hollowed-out cigars called “blunts.”
The psychoactive compound Δ9-tetrahydrocannabinol (THC), accounts for the use of cannabis as a drug and is concentrated in plant resin (most in flowering buds).
Marijuana potency (in terms of THC content) varies widely, depending on the genetic strain of the plant and growing conditions.
Potency can be increased by preventing pollination and seed production by the female plants. This marijuana is called sinsemilla (“without seeds”). Makes up 50% of confiscated marijuana. 11% considered “high grade”
#1 most widely used illegal drug in US; It is classified as a mild hallucinogen
Potency also depends on:
frequency of use
user characteristics
setting
expectations
smoking behavior

2. Hashish
Hashish is a cannabis derivative that can be smoked or eaten. It can refer to a relatively pure resin preparation with very high cannabinoid content, or a solvent extract of leaves or resin. Most potent form of marijuana Hash oil is an alcoholic extract. A drop is placed on a tobacco or marijuana cigarette. Use is fairly rare in US now less than 1% has been confiscated 2

3. History of Marijuana
Marijuana remains a controversial subject in our society—castigated by many as a gateway to the so-called hard drugs, but praised by others as an unappreciated medical marvel. Marijuana is produced from flowering hemp (Cannabis sativa). Hemp has been a major source of fiber in many cultures for rope, cloth, and paper. Hemp seeds have been used for oil and bird food. Hemp also contains 70 unique compounds known as cannabinoids, plus more than 400 other identified compounds. 3

4. Early History of Marijuana
8000 BC: first archeological record
BC: Medical and religious use can be traced to ancient China, India, and the Middle East, spreading to the Arab world.
1800’s: Napoleon’s soldiers brought it to France from Egypt. It became popular with French writers and artists. Hemp was grown and used in colonial America.
1900’s: Marijuana smoking probably came to the U.S. with Mexican and Caribbean immigrants.

5. Modern History of Marijuana
1914: Harrison Act increased taxation for grower to seller
1926: Newspaper article links marijuana use to crime
1930s: US Bureau of Narcotics launched a public relations campaign to portray marijuana as a social menace that could destroy the youth of America. The propaganda included magazine articles and anti-marijuana films such as Reefer Madness.
1936: All states regulate use, sale, and possession.
1937: Marijuana Tax Act instituted a national registration and taxation system aimed at discouraging all use of cannabis. Made use illegal.
1944: La Guardia Report downplayed serious effects
1969: Marijuana Tax Act found to be unconstitutional
1970’s: Marijuana use peaks; drops in 1980’s; rises again in 1990’s
1996: First state laws legalizing Marijuana for medicinal use.
2012: First states laws legalizing Marijuana for recreational use.

6. Phytocannabinoids
Marijuana has over 400 chemicals and ~ 70 phytocannabinoids 9-tetrahydro-cannabinol (THC) was identified as the major active ingredient in Is most pharmacologically active. Burning marijuana causes the THC to vaporize and enter the smoker’s lungs in small particles. THC is easily absorbed by the lungs, and blood plasma levels rise quickly. Effective dose and latency to onset of effects are influenced by the amount and potency of the plant used and patterns of smoking. Concentrations begin to decline as a result of metabolism in the liver and accumulation in the body’s fat stores (half life: ~19 hrs; complete elimination in 2-3 weeks). In oral use, poor absorption results in low and variable plasma levels, probably due to degradation in the stomach and first-pass metabolism (peak effect occurs ~90 mins after ingestion). THC synthetics: Dronabinol (Marinol) Nabilone (Esamet) 6

7. Phytocannabinoids Cannabigerol-type CBG Cannabichromene-type CBC
Cannabidiol-type CBD
Tetrahydrocannabinol- and Cannabinol-type THC, CBN
Cannabielsoin-type CBE
iso- Tetrahydrocannabinol- type iso-THC
Cannabicyclol-type CBL
Cannabicitran-type CBT

8. Endocannabinoids Arachidonoyl ethanolamide (AEA), Anandamide
2-arachidonoylglycerol (2-AG)
Oleamide
Endocannabinoid System Function:
Reinforcement
Dependence and/or Relapse
Alcohol
Other drugs

9. Endocannabinoid Physiology
Retrograde messengers:
carry information in the opposite direction

10. Cannabinoid Receptors
A cannabinoid receptor in the CNS was identified in 1988.
Receptors occur in many brain areas.
Cannabinoid receptors are metabotropic
work via G proteins to inhibit cAMP formation
Inhibits adenylate cyclase
inhibit voltage-sensitive Ca2+ channels
open K+ channels.
CB1 receptors
CNS (reward via mesolimbic?)
Located on axon terminals
Inhibiting many neurotransmitters
CB2 receptors
immune system (could modulate response)
Bone
adipose (fat) cells
GI tract.
Rimonabant: CB1 antagonist
CP-55,940: CB agonist

11. Cannabinoid Receptors in the Brain
Cannabinoid receptors (CB1)
cerebral cortex
hippocampus
basal ganglia
cerebellum
nucleus accumbens
Receptor Autoradiography
Brighter areas show greater
receptor density

12. CB1 gene (CNR1) Expression

13. CB1 Receptors and Mood Prefrontal Cortex Hypothalamus Amygdala
Hippocampus
Raphe nucleus
VTA
Locus Coeruleus
NPH

14. Marijuana use as a Function of Age
Risk Factors:
Emotional problems
Family problems
Drug use in household
Drug us by peers
Dislike of school
Poor school performance
Early age of first use
Early positive increases dependency
If not tried by 25 then typically never use

15. Negative Effects of Marijuana
lung damage
increased heart rate
dry eyes and mouth
impaired tracking ability
memory loss
reduced locomotor activity
hypothermia
hypoalgesia
decreased sperm cell count
decreased cognitive function
decreased educational performance
rejection of mainstream ideas
anxiety or paranoia
depersonalization
derealization
agitation
altering of mood
tolerance/addiction like properties
marijuana madness
desensitization of receptors
Amotivational syndrome
Gateway drug?
Hippocampal CB1 receptors are responsible for memory impairment

16. Marijuana Madness
Probability of Psychoses in Marijuana Users

17. Marijuana Madness
Association Model: individuals who are already vulnerable to developing psychosis have an increased likelihood of using cannabis when they are young
Causal Model: heavy use predisposes individuals to develop psychosis later in life.
Indicator-Variable Model: one or more other factors lead jointly to cannabis use and psychosis proneness. 17

18. Marijuana Tolerance Develops after high levels or regular use
May not develop uniformly to all effects
Animals exposed to THC or CB1 agonists develop tolerance
CB receptors are desensitized and downregulated following chronic THC exposure

19. Marijuana Dependence Dependence: Rehabilitation:
Difficulty in stopping use
Craving the drug
Unpleasant withdrawal symptoms
Most users do NOT become dependent
Rehabilitation:
Similar to other drug treatments
Cognitive behavioral therapy
Motivation enhancement therapy
Patients are vulnerable to relapse

20. Marijuana Withdrawal Withdrawal: Symptoms: Increased irritability
No DSM-V listing
Not life threatening but unpleasant
Some research supports notion
Begins 1 day after last dose
Lasts 4 – 12 days
Symptoms:
Increased irritability
Increased Anxiety
Decrease mood
Increased sleep problems
Increased aggressiveness
Decreased appetite

21. Positive Effects of Marijuana
reduced nausea
reduced pain
reduced MS spasticity
reduced symptoms of GI tract disorders
reduced cancer formation
reduced symptoms of neurodegenerative disorders
reduced symptoms of psychiatric disorders
CB1 antagonists can reduce obesity
Increased fear alleviation

22. History of Medicinal Marijuana
1937: after Marijuana Tax Act medicinal use of marijuana dropped so other medicines were developed
1970’s to present: increased interest in medicinal use for:
Glaucoma
Chemo-based Nausea (antiemetic)
1985: Synthetic THC, Marinol (Dronabinol) approved as antiemetic
1993: Marinol approved as appetite stimulant for AIDS patients
1999: Institute of Medicine – recommends medicinal use
2014: 23 states and DC allow medicinal use

23. The New Medicinal Marijuana*
The New Medicinal Marijuana *
Nabiximols
THC
CBD
*FDA approved

24. Cannabis and Multiple Sclerosis
Cannabidiol (CBD)
Pain
Shaking
Spasms
Spasticity
Fatigue
Sleep Quality
Mobility
Well Being

25. Cannabis and Cancer
MMP-2: enzyme that promotes spread of cancer

26. Obesity Control CB1 antagonist: AM6545 Acts peripherally
Reduces food consumption in humans and non-human animals
May be useful in treating obesity