Transcript THC - Department of Psychology

How marijuana, food and medications
affect our brain and behavior
Gary L Wenk, Ph.D.
Professor
Departments of Psychology & Neuroscience
Ohio State University
There is still botanical debate over whether there is
1, 3, or more species of cannabis.
Cannabis Indica is grown for it PSYCHOACTIVE
resins. This one may actually be a shorter, bushier
version of the plant.
Cannabis 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.
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.
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.
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.
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 very high
doses, but its structure does not resemble LSD or
any other drug formally categorized as
hallucinogen.
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.
The body has its own
endogenous cannabinoid.
Anandamide
(Sanskrit for inner bliss).
It’s found in chocolate at
low levels.
about as potent as THC.
Chocolate tree
Chemical structures of the anandamide and THC
THC
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.
Half-life is about 19 hours. Can be stored in fat cells.
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!
2/3 of metabolites are excreted in feces.
1/3 of metabolites are excreted in urine.
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.
Eating it is associated with nausea, physical
discomfort and hangover because dose level cannot
be titrated as accurately as smoking.
Stages of marijuana intoxication include:
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.
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.
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
“feeding center” (ventromedial hypothalamus) may
explain the munchies.
The Anti-Cannabinoid
Rimonabant
Chronic treatment with rimonabant produces a depression-like phenotype in the brain
Beyer et al., 2010, Neurobiology of Disease
In contrast,
in the old brain, marijuana
restores neurogenesis,
reduces brain inflammation
and improves memory.
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.
Marijuana
Receptors in
Hippocampus and
Frontal cortex
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
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 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
Does marijuana lead to psychosis?
Dosage x Gene Interaction is critical when answering this
question.
There is evidence that cannabis use is correlated
with degradation in mental health, however, only in
those with a genetic predisposition to mental illness.
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.
Older medical textbooks 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, “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.
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!)
Pot use among seniors goes up as boomers age. Grayhaired tokers turn to marijuana to relieve many problems of
aging.
Perry Parks, 67, takes a puff of
marijuana at his home in Rockingham,
N.C. The retired Army pilot suffered
crippling pain from degenerative disc
disease and arthritis before turning to
marijuana.
updated 9:42 a.m. ET, Mon., Feb. 22, 2010
MIAMI, Florida - In her 88 years, Florence Siegel has
learned how to relax: A glass of wine. A copy of The New
York Times, if she can wrest it from her husband. Some
classical music, preferably Bach. And every night, she lifts a
pipe to her lips and smokes marijuana.
Medications and Foods
Lysine-d-amphetamine
METHYLPHENIDATE (Ritalin)
Increased Release of Norepinephrine
Blockade of inactivation by re-uptake
Biphetamine
A combination of two
amphetamines; known
popularly as "black
beauties."
Marketed for its weight
loss benefits
Dexedrine
dextro-amphetamine
Most potent form of the
drug (found in Aderall)
Acts by increasing the
release of norepinephrine
and blocking re-uptake.
The brain’s
“ON”
Switch
Norepinephrine
Regulates the
Level of Arousal
NE
Amphetamine
Acute administration: Heightened alertness, euphoria,
lowered fatigue, decreased boredom, depresses
appetite, insomnia, headache, tremor
EEG waking EEG shift to higher frequencies,
Side effects: increased heart rate, fever, hypertension,
dilated pupils, sweating, seizures, dizziness, tremor,
increased respiration.
Medications and Foods
CAFFIENE
SOURCE
CAFFEINE IS FOUND IN AT LEAST 63 PLANT SPECIES,
BUT 54% OF WORLD'S CONSUMPTION DERIVES FROM
TWO DIFFERENT BEANS OF COFFEA ARABICA AND
COFFEA ROBUSTA
43% OF ALL TEA COMES FROM CAMELLIA SINENSIS.
DOSE: 1 MG/KG AVERAGE CUP OF COFFEE
INSTANT COFFEE HAS 60-70 MG; BREWED HAS 100 MG; ESPRESSO
(100 MG); DRIP HAS 150 MG; DECAF (2-4 MG).
MINIMUM STIMULANT DOSE IS BETWEEN 85 AND 250 MG.
TEA: BUDS HAVE GREATEST CAFFEINE CONTENT.
BLACK TEA HAS ABOUT 40 MG; GREEN TEA ABOUT 35 MG. DEPENDS
METHOD OF PREPARATION AND VARIETY OF TEA USED. ICED TEA
HAS ABOUT 70 MG. WHITE TEA (STEAMED RATHER THAN
FERMENTED OR ROASTED) MAY CONTAIN MORE.
CHOCOLATE (1 OZ BAR) CONTAINS 75-150 MG OF
METHYLXANTHINE (90% AS THEOBROMINE).
Effects of major xanthine derivatives
Major Source
CNS
Heart
Diuretic
Theophylline
Tea
Moderate
Potent
Potent
Caffeine
Coffee
Potent
Moderate
Moderate
Slight
Minimum
Slight
Theobromine Coco nut
LARGE DOSES: MOOD CHANGES, NERVOUSNESS,
IRRITABILITY, LACK OF ALERTNESS.
1 GM (7-10 CUPS) CAFFIENE: INSOMNIA, WEARINESS,
ANXIETY, RESTLESSNESS, SENSORY DISTURBANCES
SUCH AS RINGING IN THE EARS, MUSCLE TENSENESS,
WEAKNESS, TREMOR, CARDIAC IRREGULARITIES,
EXACERBATION OF ULCERS, DIARRHEA, NAUSEA,
APATHY.
WITHDRAWAL
HEADACHE - "WEEKEND TENSION HEADACHES"
MAY BE DUE TO LARGE COFFEE INTAKE
DURING WORKWEEK, THEN WITHDRAWAL ON
WEEKENDS.
BENEFICIAL EFFECTS
ENHANCES MENTAL CLARITY, ALLAYS FATIGUE.
CAFFEINE IS MOST EFFECTIVE IN IMPROVING
PERFORMANCE WHICH HAS BEEN DETERIORATING DUE
TO EXCESSIVE STRESS OR FATIQUE.
IT HAS LESS DRAMATIC EFFECTS ON WELL RESTED
SUBJECTS. Law of Initial Value
WOMEN IN FIRST 5 DAYS OF THEIR MENTRUAL CYCLE
HAVE ENHANCED MEMORY WITH CAFFEINE DOSE.
DRINKING 2 CUPS (TYPICAL) OF COFFEE PER DAY MAY
SIGNIFICANTLY SHORTEN THE MENTRUAL CYCLE IN
SUSCEPTIBLE WOMEN.
NEGATIVE SIDE EFFECTS
CNS: GRAND MAL CONVULSIONS CAN BE ELICITED
BY CAFFEINE AND THEOPHYLLINE.
INCREASES CORTICAL EEG ACTIVITY MAY EXPLAIN
SLEEP DISTURBANCES.
HEART: PREMATURE VENTRICULAR CONTRACTIONS
AND SERIOUS ARRHYTHMIAS.
CHOCOLATE HAS MOSTLY THEOBROMINE WITH
MUCH LESS CAFFEINE.
THEOBROMINE IS A CONSIDERABLY WEAKER CENTRAL
STIMULANT THAN CAFFEINE OR THEOPHYLLINE, WHICH
HAVE SIMILAR POTENCIES.
The Effects of Chocolate Upon
Cognition are Due to:
1. Presence of Theobromine
2. Fats induce the release of endogenous opiates
3. Presence of Amphetamine-like drug (PEA)
4. A Marijuana-like drug known as anandamide
5. Presence of Glucose
6. Presence of Estrogen-like compounds
7. Magnesium Salts for post-menopausal women
8. Anti-oxidants, flavonoids = 1 glass of red wine
Opiates
1874- MORPHINE WAS
MODIFIED BY CHEMISTS TO
YIELD HEROIN
1989 - PLACED ON THE
MARKET AS A NONADDICTING SUBSTITUTE
FOR CODEINE AND
MORPHINE
A PET image of the brain showing where
heroin is thought to act.
Naturally Occurring Opium-like Molecules
IT MAY BE REWARDING TO EAT CERTAIN
FOODS BECAUSE THEY THEMSELVES
CONTAIN OPIATES
E.G. MILK casein is converted to
BETA-CASEOMORPHIN
Salvia divinorum, whose main active ingredient is the
neoclerodane diterpene Salvinorin A, is a hallucinogenic
plant in the mint family that has been used in traditional
spiritual practices for its psychoactive properties by the
Mazatecs of Oaxaca, Mexico.
It is very potent and acts similar to heroin.
Self medicating for depression
Smoking and Depression
•Individuals with underlying or
current depressive symptoms are
more likely to experience mood
disturbances when they attempt
to quit.
•Smoking may mask an
underlying depression in some
smokers.
•Yale Study: 90% of smokers will
meet diagnosis criteria for clinical
depression.
Whole-body PET scans illustrating reduced levels of the
enzyme necessary to remove brain stimulants
The effect would be similar to taking an SSRI such as Prozac
Smoking chimp kicks habit after 16 years
Ai Ai, 27, first took up smoking after her mate died in 1989.
After a second spouse died in 1997 and her daughter was moved to another zoo, the brokenhearted chimp's health reportedly started deteriorating.
Zoo keepers say they are giving her mouth-watering food and playing pop music to
improve her mood.
"In the first few days, she squealed for cigarettes every now and then," Xinhua reported one
zookeeper at the safari park in the Shaanxi province, north-west China, as saying.
"But as her life became more colourful, she gradually forgot about them altogether."
Her new, busy lifestyle includes walking after breakfast, exercising in the evening and
being served "fried dishes and dumplings at every meal" on top of bananas, rice and
milk, he said.
Now and then, she can also borrow her human friend's walkman to listen to music.
It is not clear how Ai Ai developed her addiction, and whether she was first given cigarettes
from the same guardians who have helped her quit.
~BBC News
HERBALS
St. John’s Wort
St. John's Wort is an herb that has been used for centuries
to treat depression.
The composition of St. John's Wort and how it might work
are not well understood.
There is some scientific evidence that St. John's Wort is
useful for treating mild to moderate depression. However,
recent studies suggest that St. John's Wort is of no benefit
in treating major depression of moderate severity.
Why is St. John's Wort used as an alternative therapy for
depression?
Some patients who take antidepressant drugs do not
experience relief from their depression. Other patients have
reported unpleasant side effects from their prescription
medication, such as a dry mouth, nausea, headache, or
effects on sexual function or sleep.
Finally, cost can be a reason. St. John's Wort costs less than
many antidepressant medications, and it is sold without a
prescription (over the counter).
St. John’s Wort
• “More reviews than actual studies.”
• “Works in Europe but not in the USA.”
• Inhibits reuptake of 5-HT, DA & NE –
similar to Prozac, has a stimulating effect
on mood and cognition.
• Active ingredient may be either
hyperforin or hypericin
St. John’s Wort
• NIMH study – 8 weeks of therapy @ 900
mg/day, 336 patients
• HAM-Depression scale
• St. John’s Wort was less effective than
placebo control
• Most common side-effects: anorgasmia
and urinary frequency
Content of Hypericin in Commercial
St. John’s Wort Products
0.3
0.25
%
0.2
Stated
Actual
0.15
0.1
0.05
Nature's
Resource
Kira
Your Life
Solgar
Anything we consume—the drugs we take, the foods we
eat—can affect how our brain functions and,
subsequently, how we think and feel.
 The distinction between what is considered a drug, (i.e., something that your
brain wants or needs in order to function optimally, ) and food, (i.e.,
something that your body wants or needs in order to function optimally), is
becoming increasingly difficult to define.
 The routine use of some substances, such as stimulants and depressants, is
so universal that most students do not even consider them to be drugs, but,
rather, actual food.
 Is coffee, tea, tobacco, alcohol, cocoa, or marijuana a nutrient or a drug?
 For many people, the distinction has become rather blurred.
Questions?