Marijuana
Chapter 11
 Cannabis sativa
 Tetrahydrocannabinol (THC)
History of Marijuana
Oldest non-food crop cultivated by man/woman
 Earliest archaeological records from Taiwan, 10,000 yr
(stone age) evidence of hemp fiber use
 Pottery, clothes, shoes, bow strings, paper (105 A.D.)
 Ts’ai Lun ridicule!
 Use Spread throughout Asia, the mid East, and
eventuallyEurope.
History of Marijuana- Religious and
Medical use
 Also originating in China…spread about 200 BC with
Scythians
 warlike Middle Eastern tribe, gave us word “cannabis”
 used in cleansing ceremony after funerals
 threw hemp seeds on heated rocks inside tents &
inhaled vapors
Early History
 India
 Bhang--tea
 Ganja—pipe
 Charas--hashish/hash
History of Marijuana
 Most infamous use by Muslim sect founded by
Hasan-Sabbah (Hashishin)
 secret assassination
 gave us words hashish & assassin
 Hebrews also used cannabis
(Old Testament in Exodus)
 God told Moses to make holy oil containing cannabis
History of Marijuana
 France in mid 1800s with "Club des
Hachichins"
 writer Gautier offered reward to anyone who invented
a new pleasure – was given hashish by a doctor
 Victor Hugo, Alexander Dumas
 consumed large quantities of hash-like material
 wrote accounts of their experiences
History of Marijuana
 In Early U.S., primarily for rope and canvas (George
Washington), Minor medicinal use
 Prohibition increased use of MJ..NYC “Tea Pads!”
The Bureau of Narcotics
Commissioner of Narcotics, Harry Anslinger -crusade against
marijuana
1920s & 1930s - major attention - drug of violent crime
& danger to society
History of Marijuana
1937 Marijuana Tax Act
 made possession of marijuana without having paid special tax illegal
 classified marihuana as a controlled substance. Needless to say most doctors and dentists
stopped using products covered by this law.
What we have lost
Various Uses
Cannabis L.
Stems
Paper
Plastics
Fuels
Textiles
Animal Bedding
Mulch
Seeds
Vegetable matter
Bird seed
Industrial hemp
Flour and cereals
Incense
Body care products
Non diary milk/cheese
Nut butter
Salad dressing
Sports Bars/
Protein Powder
Margarine
Paints/ Varnishes
Detergents
History of Marijuana
Early 1940s
 NYC Mayor Fiorello La Guardia
 set up commission of experts to determine
consequences of marijuana use
 Final report - marijuana fairly minor intoxicant with
few side effects even when used excessively
 Report ridiculed by Anslinger
A harder attitude- 1950’s-60’s

VI. THE 1950's: HARSHER PENALTIES AND A NEW RATIONALE-THE "STEPPING STONE" THEORY

1951 Congress passed -the Boggs Act . .much harsher penalties for all drug violators. marijuana and other narcotics were
lumped together

First offense 2 - 5 years

Second offense 5 - 10 years

Third and subsequent offenses 10 - 20 years

Fine for all offenses $2,000.00
Boggs stated: "We need only to recall what we have read in the papers in the past week to realize that more and more younger
people are falling into the clutches of unscrupulous dope peddlers . . . .“
Perhaps Commissioner Anslinger best described the prevailing climate when he stated:

Short sentences do not deter. In districts where we get good sentences the traffic does not flourish....

There should be a minimum sentence for the second offense. The commercialized transaction, the peddler, the smuggler, those
who traffic in narcotics, on the second offense if there were a minimum sentence of 5 years without probation or parole, I
think it would just about dry up the traffic
History of Marijuana
 Marijuana comeback: late 1950s to early 1960s
 Now most broadly used illicit substance in U.S.
 35-40% of Americans having tried
 Numerous states have compassionate use laws
Marijuana use exploded in the
1960s
And use continued at high rates into
the 70’s through today
Percent High School Seniors reporting
Marijuana use during their Senior year
Percent Using
60
50
40
30
20
10
0
75
80
85
90
95
00
05
Time/CNN Poll 2006
 80% approve of medical use of marijuana
 72% say that marijuana possession should lead to fine, not jail
 47% say that they have tried marijuana at least once
A changing Attitude? Law Reforms:
 2006, Recreational Marijuana use on ballot in Colorado and Nevada
 Defeated in both cases

January 02, 2009 Massachusetts
On Nov. 4, a majority of voters in Massachusetts chose to decriminalize possession of
small amounts of marijuana. Those in possession of less than an ounce of marijuana are
no longer charged with a criminal offense, but instead face a $100 fine.
U.S. Drug laws TODAY
The International perspective-The
Dutch Experience
 Marijuana is NOT legal, but laws are not enforced for Coffee
shops in Amsterdam
 Over 1000 shops are now licensed in the Netherlands
 Cannot advertise
 Cannot sell to minors
Current MJ World Laws
The Future?/ Politics of Marijuana
Preparations of Marijuana
 Leaves, stems and
flowering buds of cannabis
sativa
 Most of the THC is in the
buds
Cannabis Preparations
Name
Part of Plant
THC
Marijuana Leaves, stems
1-3 %
Sinsemilla Sterile flower
heads
Ganja
Hashish
Cannabis resin
3-8 %
10-15 %
Cannabis/ Resin concentrate 20-60 %
Hash Oil (alcohol extract)
Preparations of Marijuana
Hash Oil - boil with solvent, solvent then strained out
 THC concentration as high as 60% - 70%
 Becoming more popular - ease of smuggling
Active Agents
-9-THC
-8-THC
Cannabidiol
Active Metabolites
Active Agents
 Cannabidiol - slows metabolism of THC
increases duration
 converted to THC when burned
 may have neuroprotective, anticonvulsant and
anti-psychotic effects

Pharmacokinetics
 Administration
 Inhalation – Smoke
 Oral – Tincture, Eating, Tea
 Marinol
 Oral-mucosal
 Sativex
To meet demands for Sativex, GW
Pharmaceuticals has increased production of
cannabis at its fortified greenhouses to 60t/y.
(Source: ABPI)
 Distribution
 Everywhere as it is highly
lipophilic
 Flies across BBB
Pharmacokinetics of THC
 Rapid absorption in lung
 2-4 hr duration of action
 Erratic absorption after oral admin.
 Great persistence in tissue: up to 30 days after a single dose
 Detection in urine 10-14+ days after a single dose; >21 days
after chronic use
 Distribution
 Everywhere as it is highly lipophilic
 Flies across BBB
Metabolism & Clearance
• Binds to proteins and fats
• Slow metabolism in liver
• Metabolites remain detectable for a week –
three weeks
• Primary metabolic products may be more potent
(11-OH- 9-THC)
Mechanism of Action
 Mostly unknown until the late 1980s
 1988 – Isolated the receptors
 1992 – Discovered the first neurotransmitter for that receptor
 THC binds to and agonizes cannabinoid receptors
 Anandamide & 2-AG are the NTs for cannabinoid
receptors
 Anandamide : The brain’s own marijuana (from Ananda: Hindu
word for bliss)
 Works as a neuromodulator/ and “retrograde NT”
Two Receptor Types
CB-1 Receptor
CB-2 Receptor
 Mostly in periphery
 Found primarily in immune
system
 Found on heart – protects
from inflammation?
oLocated in CNS and PNS
CB1 receptor hot spots
THC is a retrograde CB1 agonist- works on
the presynaptic terminal to modulate NT
release
Physiological Effects
of Marijuana
Physiological effects
 Increase in HR & drop in BP
 Produces dry mouth & occasional dizziness
 Reddening of eyes (dilation of vessels in cornea)
 No permanent adverse cardiovascular effects
 People with heart disease should abstain
 Increased risk for heart attack four an hour after smoking
 Appetite increased
 May be related to actions on the Hypothalamus
 or nucleus accumbens- when stimulated by cannabinoids there
is an increase in the reward value of natural rewards.
PSYCHOLOGICAL EFFECTS:
Low - Moderate Doses
Disinhibition
 STM impairment
Relaxation
 Balance impaired
Drowsiness
 Decreased muscle
strength
Exhilaration, euphoria
sharpened humor
 Small tremor
Sensory - perceptual changes
 Poor on complex tasks
 Overestimate time passage
(e.g., driving)
Higher Doses
 Psychotomimetic
 Pseudo hallucinations
 Synesthesias
 Paranoia
 Agitation/panic
 Disorganized thoughts
 Confusion
 Impaired executive
function
 Increased impulsivity
 Impaired judgment, slower
RT
 Pronounced motor deficits
Side Effects of Marijuana
 THC suppresses immune system, but not enough to
increase risk of infection it appears.
 Lowers testosterone levels & sperm count as well as
estrogen
 Crosses placental barrier
◦ Lower birth weight
◦ Some evidence suggests a relation between
mother smoking while pregnant and childhood
cancer
 Most severe side effects
◦ Respiratory - can lead to asthma & bronchitis
◦ Anxiety/panic in some users
THC Toxicity
 Almost impossible to OD
 THC not toxic in this sense
 Pot smoke contains more tar than cigarette smoke
Data on cancer is very mixed – recent studies show no relationship
Does one smoke the same?
 THC found to kill cultured hippocampal cells, but so far
not in other cells high in CB receptor density
 Effect reversed with NSAIDS
 Possible mechanism for memory loss
THC – Tolerance & Dependence
 Tolerance develops with heavy long-term use
 Reverse tolerance in consistent users
 Cross tolerance with sedatives - alcohol
 Dependence – mild (like SSRIs)
 Mild withdrawal symptoms in humans, with irritability,
depression, sleep disturbances, nausea, diarrhea,
sweating, tremors, reduced food intake, and
salivation
 5% of heavy users may experience it
 30 mg THC / 4 hrs / 10-20 days 15+ joints per day (unusual
levels of intake)
 Begin within 48 hours after cessation and lasts 2 – 10 days
Highly Debated Effects
 Amotivational Syndrome
 Amotivational Syndrome is a theoretical condition that
proposes the heavy use of marijuana may alter a smoker’s
motivations, goals, and possibly personality.
 Most research has not found this to be true
 When it appears to exist, It may be psychopathology independent of use
What is Amotivational Syndrome?
 Amotivational Syndrome is a theoretical condition that proposes
the heavy use of marijuana may alter a smoker’s motivations,
goals, and possibly personality.
 Better put, this syndrome may cause "... apathy, loss of effectiveness, and diminished
capacity or willingness to carry out complex, long-term plans, endure frustration,
concentrate for long periods, follow routines, or successfully master new material.Verbal
facility is often impaired both in speaking and writing. Some individuals exhibit greater
introversion, become totally involved with the present at the expense of future goals and
demonstrate a strong tendency toward regressive, childlike, magical thinking.“
– McGlothin, W.H.
History of Amotivational
Syndrome
 The 1960’s are associated with an
explosion of the use of marijuana.
 Peak use was surveyed in 1979 with
24 million smokers.
 Before this time, any record of
amotivational syndrome was
completely nonexistent.
Case Histories
 The concept of this syndrome first appeared in the 1960’s with a
few case histories.
 However, these case histories were unable to show:
a. How common amotivational syndrome is.
b. Whether marijuana caused the change in motivation.
c. If a change did occur, did it effect all facets of motivation or is it
specific only to certain forms of motivation.
 What do you think?
What is the culprit?
 The big question is which comes first, the
marijuana or the loss of motivation?
 Lets look at a few surveys conducted on
college and high school students.
Evidence continued…
 A study among workers suggests that marijuana use can be
hazardous to working or to a motivation to work
 Users had 55% more accidents, 85% more injuries, and a 75%
increase in absenteeism
 (National Institute on Drug Abuse)
Survey Research
 A survey was conducted on 2000 college students in 1974 by
Brill, N. et al.
 The researchers concluded that there was no difference in
grade point average or academic success between smokers
and non smokers.
 However, the marijuana smokers surveyed did have more
trouble deciding on career goals and many did not pursue
professional degrees.
Laboratory Studies
 Mendelson et al, 1974, conducted an experiment in which 10 casual and 10
heavy cannabis smokers were observed for 31 days.
 They were given access to as many marijuana cigarettes as they earned through
a simple operant task which involved pressing a button to move a counter.
 The researchers found that all subjects earned the maximum amount of points
each day and output was unaffected by marijuana smoking.
 Mendelson et al concluded that: "our data disclosed no indication of a
relationship between decrease in motivation to work at an operant task
and acute or repeat dose effects of marihuana"
The Jamaican Study ( 1976)
 A study performed by Rubin and Comitas 1976, examined the effects of marijuana on
the performance of Jamaican farmers who regularly smoked marijuana in the belief that
it enhanced their physical energy and work productivity.
 They used videotape to track the farmers movements and biochemical measures of
exhaled breath to asses caloric expenditures before and after getting high.
 After smoking ganja the workers engaged in more intense and
concentrated labor.
 but this was done less efficiently, especially by
heavy users. Looking for your pencil when it’s behind your ear?
 "In all Jamaican settings observed, the workers are motivated to carry out difficult tasks with no decrease in heavy physical
exertion, and their [mistaken] perception of increased output is a significant factor in bolstering their motivation to work.“
-Comitas
Debatable issues- Gateway Drug

The gateway hypothesis holds that consumption of

abusable drugs progresses in orderly fashion through several

discrete stages

Young et al. observed that marijuana was the first drug used by 42% of

a sample of delinquent youths.
Debatable issues- Gateway Drug- Most
well-designed studies suggest this is false.

The entire sequence, which is exhibited by only a small minority of drug users, begins with beer or wine and
moves progressively through hard liquor or tobacco, marijuana, and finally hard drugs. Each stage is thus a
component of both a temporal sequence and a hierarchy.

This claim has not been empirically supported, however. Researchers have reported that marijuana use is not a
requirement for progression to hard drugs.

Golub and Johnson (5) found that 75% of inner-city heavy drug users began using cocaine before using marijuana.
These authors also report that1%–4% of hard drug users skipped both the alcohol/tobacco and marijuana stages
(6).
Mackesy-Amiti et al. (7) reported that 39% of their sample started using marijuana after they had used hard
drugs.
 Blaze-Temple and Lo (8) reported that 29% of their sample began using marijuana after having used heroin,
stimulants, or LSD.

“Common liability model” is a better explanation
 Alcohol and cigarettes are stronger gateway drugs if one accepts the data

Debatable issues- Gateway Drug vs
common liability model

Alternatively, abuse of illicit drugs,

whether or not preceded by use of licit compounds, may

be more parsimoniously explained by their availability in

the social environment and the level of the individual’s liability

that is common to all abusable substances. For example,

conduct problems in childhood presage consumption

of all classes of abusable drugs. Genetic (9–12),

neurophysiological (13, 14), neurochemical (15, 16), and

behavioral (17, 18) investigations have shown that the

same factors are associated with consumption of licit and

illicit drugs. Indeed, 100% of the genetic variance in the

risk for diagnosis of substance use disorder is common

acros
Medical Marijuana
 1998 IOM (inst of Med.) report concluded that there is scientific
evidence for medical use
 Analgesic
 Anti-emetic
 Anti-spastic
 Appetite Stimulant
 Glaucoma-not particularly effective
 Tumor suppression? (lung cancer)
 Seizures? –THC & Cannibidiol protect against neurotoxicity
Medical Marijuana
 Many states have compassionate use laws
◦ California, Washington, Oregon, Nevada, Alaska, Vermont, Maine,
Colorado, New Mexico, Montana, Rhode Island, Maryland
 Physicians “recommend” marijuana and patient buy it at
buyers clubs.
◦ Would lose license if prescribed
 2003 Gallup Pole – 75% for medical use, 66% against
legalization
 2005 study of physicians'’ attitudes
◦ 36 % were in favor of legal prescription
◦ 26% were neutral
The debate continues
Adverse Effects of Marijuana:
Chronic Effects
 Lung damage-Bronchitis; Lung cancer?
Carcinogens in smoke
 Marijuana
 Tobacco
 Vinyl Chloride
 Vinyl Chloride





5 ng
D-M nitrosamine 75 ng
M ethylnitrosamine 27 ng
Benz-anthracene 75 ng
Benz-pyrene
31 ng



12 ng
D-M nitrosamine 84 ng
M ethylnitrosamine 30 ng
Benz-anthracene
43 ng
Benz-pyrene
21 ng
Dependence on Marijuana
 Tolerance
 Withdrawal syndrome
 Irritability, mood changes
 Sleep disturbances
 Loss of appetite, nausea
 5% heavy users: 15+ joints per day; “more or less
permanently stoned” House of Lords Cannabis report (2000)
Adverse Effects of Marijuana:
Chronic Effects
 Cognitive deficits?
Cognitive deficits
 Deficits on tests of memory, learning, word fluency
(producing words in a particular category), and processing
speed persist 48+ hours after last use in chronic marijuana
users (Croft, et al., 2001)
 Heavy users who begin smoking before age 17 show more
severe deficits (Pope et al., 2003)—but many accounts are
possible
Costa Rican Study
 This study performed by Carter et al. 1980 that compared
Costa Ricans’ employment history of heavy users to nonusers.
 The comparison showed that non-users were more likely to
have a stable employment history, have received promotions
and raises, and to be in full-time employment
 Users were more likely to spend more than their incomes
Costa Rica cont.
 However, when comparing only users, a relationship between
average daily marijuana consumption and employment presents a
conflicting amotivational hypothesis.
 Those "who had steady jobs or who were self-employed were smoking more
than twice as many marijuana cigarettes per day as those with more
frequent job changes, or those who were chronically unemployed",
indicating that "the level of consumption was related more to relative
access than to individual preference"
What does this all mean?
 Evidence of Amotivational syndrome from these field studies are usually interpreted as
failing to demonstrate the existance of an actual syndrome.
 Here are a few problems with the evidence:
1. Sample sizes are too small to exclude the possibility of an effect occurring among a
minority of heavy users.
2. Cohen (1982) argues that the heavy users come from socially marginal groups.
 Therefore, the cognitive and motivational demands of their everyday lives were
insufficient to detect any impairment caused by chronic cannabis use.
Laboratory Criticism
 There are a few obvious weaknesses in Mendelson’s experiment.
1. The period of ‘heavy’ use was only 21 days, which is inconclusive with the
amount of years that many of the subjects in the field studies endured.
2. The subjects were all healthy, young cannabis users with a mean IQ of 120
and nearly three years of college education.
 During debriefing, many of the subjects reported that they were
motivated to perform well to demonstrate that marijuana does not have
any affect on their performance.
In Conclusion…
 The evidence of Amotivational Syndrome is extremely vague
in all facets of research.
 The small number of field and experimental studies were
unable to show convincing evidence to support such a
syndrome.
 In conclusion, if there is such a syndrome, it is specific only
to a few heavy users and is a very rare occurance.