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
Cannabis
The term
marijuana
comes from the
Spanish or
Portuguese
word meaning
intoxicant.
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
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.
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 1020% as much
THC as is
found in the
resin.
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.
Resin (dew) on leaves
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.
Bhang: A drink popular in India
made of cannabis leaves, milk,
sugar and spices, has 2-5% THC.
Kief: (Arabic kaif ‫ كيف‬meaning
"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.
Cannabinoids
Background
History &
Prohibition
Mechanisms of Action
Acute Behavioral &
Physiological Effects
Abuse & Effects of
Chronic Exposure
Medical Use
high-resolution scanning micrograph of cannabis
Related Substances
An 8000-year time line of
cannabis use around the world
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.
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.
Use in Judaism and Christianity is debated by scholars. The herb of
interest is most commonly known as kaneh-bos (‫ֹשם‬
ֶׂ ‫ב‬-‫ ) ְקנֵה‬which 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.
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”
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.
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.”
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
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 antinarcotic 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.
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.”
U.S. Federal Bureau of Narcotics public service
announcement used in the late 1930s and 1940s.
1936 film
Marihuana
A good girl goes to a
party, smokes marijuana,
and then goes skinnydipping 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
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.
Video collection of 1930’s antimarijuana movies.
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.
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
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.
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)
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).
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)
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.
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.”
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.
Norml.org – a group working to reform marijuana laws
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.
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.
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)
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
FBI, Uniform Crime Reports
Probability of initiating marijuana
use as a function of age
Psychopharmacology Fig 13.15 2005
Use in Columbus, Ohio
Juveniles - Among Franklin County 12th graders
surveyed in 2003, 21% reported regular use of
marijuana (monthly or more often).
Percent of College
Students Using Marijuana
in 2004
Past Month
18.9%
Past Year
33.3%
Lifetime
49.1%
(Office of National Drug Control Policy)
Cannabinoids
Background
History & Prohibition
Mechanisms of
Action
Acute Behavioral &
Physiological Effects
Abuse & Effects of
Chronic Exposure
Medical Use
high-resolution scanning micrograph of cannabis
Related Substances
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.
PRIMARY
AGENT
DELTA 9-TETRAHYDROCANNABINOL (THC) IS
CONCENTRATED IN THE RESIN OF THE PLANT.
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.
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.
Chocolate tree
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
Chemical structures of the
endocannabinoids anandamide and
2-arachidonylglycerol (2-AG)
Time course of plasma THC
concentrations
THC in a sesame oil
suspension
Time course of plasma THC
concentrations
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.
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.
Location of endocannabinoid receptors in a rat brain
CB1 receptors (red) are widely distributed in the brain.
K. MACKIE/UNIV WASHINGTON, Science, 2006
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.
May act presynaptically to
reduce the release
of glutamate and
GABA
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.
May act presynaptically to
reduce the release
of glutamate and
GABA
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.
http://www.endocannabinoid.net/videoAnimation/EndocannabinoidBiology.aspx
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
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!
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.
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)
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.
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!
Physiological Changes
Tachycardia (increased heart rate)
Enlarged pupils (in some users)
Dryness of mouth and throat
Reddening of the eyes
Inconsistent blood pressure changes
Eating Changes (the Munchies)
The presence of the cannabinoid receptor in the
ventromedial hypothalamus may explain the
munchies.
• 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.
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).
Psychomotor Performance
Can also impair psychomotor performance,
especially in demanding tasks such as
driving.
http://youtube.com/watch?v=NCgR_-qC-Ss
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.
Effect on Memory
One consistent alteration in function is on shortterm 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.
Oral THC produces a dose-dependent
impairment in explicit memory
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.
Cannabinoids
Background
History & Prohibition
Mechanisms of Action
Acute Behavioral &
Physiological Effects
Abuse & Effects
of Chronic
Exposure
Medical Use
high-resolution scanning micrograph of cannabis
Related Substances
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.
Desensitization of cannabinoid receptors
produced by chronic THC exposure
0 Days THC
(Control)
3 Days THC
7 Days THC
14 Days THC
21 Days THC
Psychopharmacology, 2005
Time course of overall withdrawal discomfort in
heavy marijuana users
IRRITABILITY, VOMITING, NAUSEA, DIARRHEA, SLEEP DISTURBANCES
Medical Concerns
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
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).
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 breathholding. (Possibly ingest less irritants in vapor,
ex. hookah).
Evidence that marijuana smoking increases risk
for head, lung, and respiratory tract cancers.
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.
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.
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
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.
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 19-24 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
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).
Does marijuana lead to
?
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.
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.
Reefer Madness (1936) - A man becomes
completely insane after heavily using
marijuana.
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….
These included the following (in order of frequency):
10.
9.
8.
7.
6.
5.
4.
3.
2.
Growing long hair
Masturbation
Driving a car
Taking a sex education class
Having sexual intercourse
Beer drinking
Dancing
Tobacco use
Kissing
And the most frequent thing they did that may have
correlated best with psychosis…
1. Watching late night television!!
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 17-200 marijuana cigarettes per
day! (1 joint ever waking 5 mins!)
This is also correlational evidence.
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
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.
Shen-nung pen ts'ao pei yao i fang ho pien
(Herbal and Prescriptions)
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).
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.
1975 Medications containing pure THC were found to be effective in
reducing severe nausea caused by anti-cancer drugs.
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.
Hempfest 2004 Seattle, Washington
(AFP/Getty Images/Ron Wurzer)
Cannabinoids in Neuroprotection
Cannabinoids are both neuroprotective and antiinflammatory 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
Cannabinoid
Receptor
Activation
Decreased Release
Cannabinoid Neuroprotection
Against Excitotoxicity
Glu
(excitatory)
Excitotoxicity
Saved
Cell
Cell
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
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
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.
Prohibition
Doctors may not "prescribe" marijuana for
medical use under federal law, though they
can "recommend" its use under the First
Amendment.
CannabisFacts.ca - Canadian Org
The Anti-Cannabinoid
Rimonabant
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.
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
Terpenes
Marijuana, catnip, wormwood, mints are all in the
family of terpenes.
Thujone (wormwood)
Delta-9-THC
Various uses of Catnip
tea for medicinal
purposes: curing
chronic bronchitis,
diarrhea, upset
stomach, infant colic,
flatulency, spasms, and
“various lower type
female disorders”.
Catnip’s active ingredient,
nepetalactone causes mood
elevation and sedation in
humans and euphoria in cats.
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.
Wormwood
Bitter taste (due to absinthin). Has a
taste threshold of one part in 70.000.
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.
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.
1896 poster
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.
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.
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.”
The End
Cab Calloway – Reefer Man (1933)
Questions to Holly Brothers.23@osu.edu
Links
Office of National Drug Control Policy
www.WhiteHouseDrugPolicy.gov blog at www.PushingBack.com
Research
http://www.whitehousedrugpolicy.gov/links/topical.html#research
Columbus Ohio Demographics
http://www.whitehousedrugpolicy.gov/statelocal/oh/ohcolumbus.pdf
Deliniated Ohio Laws
http://www.norml.org/index.cfm?wtm_view=&Group_ID=4557
Video History of Cannabis
http://video.google.com/videoplay?docid=8410436555236949417&q=marijuana&hl=en
Cab Calloway - The Reefer Man – 1933
http://www.youtube.com/watch?v=vvsbqjrRNvE
Your Brain on Drugs 1980’s Commercial
http://www.youtube.com/watch?v=i2_fS8KLTcM
Hemp for Victory – US pro-hemp propaganda during WWII
http://www.youtube.com/watch?v=VYFZEkVeewY
The Terrible Truth (1951) – Gateway Drug
http://www.youtube.com/watch?v=_ojzi0c8BhQ&mode=related&search=