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 10-20% 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.

PreparationsMarijuana: 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 كيف meaning "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 short-term 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 systemReproductionCognitionPsychological effectsAmotivational 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):

9. Masturbation8. Driving a car7. Taking a sex education class6. Having sexual intercourse5. Beer drinking4. Dancing3. Tobacco use2. Kissing

And the most frequent thing they did that may have correlated best with psychosis…

1. Watching late night television!!

10. Growing long hair

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!)

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.

Pot use among seniors goes up as boomers age. Gray-haired tokers turn to marijuana to relieve many problems of aging.

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 NorepinephrineBlockade of inactivation by re-uptake

BiphetamineA combination of two amphetamines; known popularly as "black beauties."

Marketed for its weight loss benefits

Dexedrine

dextro-amphetamineMost potent form of the drug (found in Aderall)

Acts by increasing the release of norepinephrineand blocking re-uptake.

NE

Norepinephrine Regulates the Level of Arousal

The brain’s “ON” Switch

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

CAFFIENECAFFIENE

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 COFFEEINSTANT 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).

Major Source CNS Heart Diuretic

Theophylline Tea Moderate Potent Potent

Caffeine Coffee Potent Moderate Moderate

Theobromine Coco nut Slight Minimum Slight

Effects of major xanthine derivatives

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 IRREGUL ARITIES, 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 NON-ADDICTING SUBSTITUTE FOR CODEINE AND MORPHINE

A PET image of the brain showing where heroin is thought to act.

IT MAY BE REWARDING TO EAT CERTAIN FOODS BECAUSE THEY THEMSELVES CONTAIN OPIATES

E.G. MILK casein is converted to

BETA-CASEOMORPHIN

Naturally Occurring Opium-like Molecules

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 broken-hearted 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

HERBALSSt. 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

0.05

0.1

0.15

0.2

0.25

0.3

Nature'sResource

Kira Your Life Solgar

StatedActual

%

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.

Anything we consume—the drugs we take, the foods we eat—can affect how our brain functions and,

subsequently, how we think and feel.

Questions?