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Marijuana and Health - an update of research results by Peter Gormand Transcribed 5/9/90 by The Dak as originally printed in High Times, 11/87 Holiday Inn, Cambodia BBS - 209/456-8584 - 300/1200/2400 - 8/N/1 - 24 Hours =========================================================================== Although cannabis has been subjected to endless study and clinical analysis, very little can be stated categorically as to its effect on health. The scientific literature is confusing and contradictory, and the marijuana issue polarizes emotions, making moralists of scientists. Since every researcher is aware that his or her work is going to be used somehow by someone in the case for legalizing or not legalizing public consumption, personal and political bias seems to filter through the work. Marijuana and its compounds are not simple drugs. What shows up theoretically doesn't always appear in the lab; what appears in the lab doesn't always appear in clinical practice. Being a psychotropic, its effects can vary widely from user to user. Perhaps it confounds science because it is a psychotropic. Spiritual aids are rarely classifiable. In a time when designer cocktails can blow you into deep space with a single dose, and crack makes instant addicts of nearly everyone who smokes it, the issues of marijuana and its significance to health seem trivial. But here at High Times, where pot is still king, we thought you should be appraised of developments in the field. First things first: Nobody's found web-footed babies, tiny testes, atrophied brains, shrunken limbs or 44Ds in the average pot-smoking male's contribution to conception. But that doesn't mean perpetual intoxication has the green light. So sit down, read this and get some of the facts. Note: Research studies involving humans referred to in this report - with the exception of a section on pregnancy and birth - deal with adults. As with all drugs, and specifically intoxicants, researchers across the board recommend against the use of pot by pre-pubescent and pubescent children. Accumulation ============ Of the 420 known components of Cannabis, the major, if not the only, active component is Tetrahydrocannabinol, commonly called THC. This is a group of cannabinoids, sixty-one of which have been identified, many of which produce some biological activity. Delta 9 THC, the principal active component in natural cannabis, produces almost all of the characteristic effects of grass. It is by far the most often studied of the active isomers found in pot. The natural cannabinoids are relatively insoluble in water but dissolve in fats and fat solvents and are called lipid-soluble. When smoked, the THC is rapidly absorbed by the blood in the lung; high concentrations of THC there begin to fall rapidly within 30 minutes of smoking. From that point on elimination slows considerably. Roughly 25 percent of the initial THC and its metabolites remain in the body after a week, and traces from a single dose can be found for up to thirty days. In the body, the THC binds to fatty acids where it remains, unchanged, until it passes back into the blood stream for elimination. Generally, lipid-soluble compounds are completely neutralized when bound of fatty acids, but some controversy exists over whether this rule holds true for the psychoactive ingredients of marijuana. There is no medical question about its distribution area - the fat cells of the entire body from the toes to the brain - or that it remains unchanged while bound there. The questions are what effect the THC has on the user while it waits for elimination, and whether the repeated administration of even small doses may lead to an accumulation of drug which is potentially higher than levels reached at any time after a single dose. On one side of the argument, many researchers feel that general toxicity studies have shown marijuana to be one of the safest drugs ever studied for cumulative effects. Another group feels that since so much is not understood about how the THC acts on the brain, it is possible that minute doses of active THC released back into the system may have a continued toxic effect. Reese T. Jones of the University of California at San Francisco said in recent correspondence that "When you say active, right now, that's an unanswerable question...it's in the brain, there's no question of that, but the activity issue, that depends on whom you talk to." The problem encountered with the issue of accumulation is typical of issues involving marijuana. There is continued debate over long-term effects to both the chronic and casual user. Obviously, in areas of concern, researchers find the chronic user at more risk. Few studies have shown serious concern regarding long-term effects for the light smokers, even among antagonists to the drug. Acute Effects of Cannabis ========================= Little controversy exists in discussion of the short-term or acute effects of smoking marijuana or hashish. These occur while high levels of THC are still in the metabolism. These short-term effects can include an increased pulse rate, giddiness, euphoria, hallucinations, reddening of the eyes, dryness of the mouth, sudden hunger, heightened sensory perception, sedation and conceptual changes. A number of these - in combination - are what is called "getting high." Along with these generally pleasant changes, the user may also experience nausea, anxiety, paranoia, changes in blood pressure and body temperature, disorientation, confused states, short-term memory loss, temporary alteration of motor skills, changes in depth perception, poor attention span and depression. Some researchers have found that smoking grass inhibits verbal and analytical skills in users while facilitating nonverbal tasks. Additionally, marijuana, when coupled with other substances, can have an addictive effect. Alcohol and marijuana in combination can render the user dysfunctional; marijuana used in combination with barbituates can prolong the effect of the barbituate, and, in extreme cases (at least theoretically), cause non-lethal doses of barbituate to become lethal doses. In general, researchers agree that these effects, both pleasant and unpleasant, are temporary. Even acute anxiety or paranoid reactions can be managed with verbal reassurance. A study of 700,000 hospital admissions in the United States in 1971 revealed that only 10 of those were for acute cannabis reaction. Certain tasks requiring fine motor skills - driving a vehicle or operating certain types of machinery and equipment - should not be undertaken while under the influence of marijuana. How long the driver will be impaired remains under debate, but even the most liberal thinkers acknowledge that driving should not be undertaken for three to four hours after smoking. The other end of the spectrum puts it at more like sixteen hours - depending on the individual, the quantity and quality of cannabis smoked and other factors. In certain circumstances - people taking medication which cannabis might interfere with - individual may have a short-term reaction deleterious to their health, and judgement should be exercised in the use of cannabis. The effects mentioned above are considered to be of short duration and depend on the potency of the cannabis, the setting, and the user's orientation and state of mind at time of use. Generally, some of the negative - and, sorry to say, the positive as well - effects are expected to be more pronounced in the newer user rather than in the more experienced individual. Long-Term Effects of Cannabis Use ================================= Pulmonary Effects: The lungs are the natural target for the harmful effects of smoked material, and among chronic smokers, chronic bronchitis and mild airway constriction occur regularly. There are several known carcinogens in marijuana smoke and certainly more tar - though no nicotine - and incidental particulates than in tobacco smoke. But as yet there has not been a single instance of human lung cancer attributable solely to marijuana use. The bronchial problems mentioned are somewhat more related to the act of smoking than they are to the active ingredients in grass, and the use of a water pipe can eliminate most of them. Theoretical problems with fungi found in marijuana - Aspergillus, among others - are repeatedly mentioned in the literature. However, there has only been one official case of actual Aspergillus poisoning, and that was in a man whose immune function was depressed as a result of intensive chemotherapy treatments. Fungi can be killed by cooking the marijuana before use (100 degrees celsius for 30 minutes), though in most healthy people this has not shown itself to be a problem. Marijuana smoke has been shown to inhibit pulmonary antibacterial defense systems, but the toxin involved is reportedly related to the smoke itself and not to any psychoactive component in the drug. I recently spoke with Dr. Tashkin of UCLA, one of the leading pulmonary specialists in the country, and asked him what the real risks - long-term - to the smoker were. "We've found changes in the airways of marijuana smokers which are also found in the airways of cigarette smokers who go on to develop cancer...it doesn't mean they will develop cancer. That hasn't been shown to have happened yet, its just a marker of increased risk we've found in smokers using two or more joints a day for more than five years. The smoking of marijuana can lead to pulmonary complications, and that really is the bottom line. Of course, to find out the real risk we're going to have to rely on doctors asking their patients as to whether or not they smoke. We'll have to record that information, and that information will have to be made available to pathologists, and they will have to study the results." Heart and Cardiovascular Effects: ================================= Smoking marijuana clearly changes the heart function. The most common and important of which is through tachycardia - a speeding up of the heart rate that is sometimes accompanied by temporary changes in blood pressure - and, occasionally, by ventricular fibulation - a condition where ventricle contractions become uncoordinated. These effects have been shown to be temporary and reversible and not problematic in healthy individuals. In certain circumstances, however, they could lead to serious complications - specifically in people with heart problems or angina pectoris. Those taking medication for the heart are recommended to avoid smoking cannabis, since the THC may interfere with those medications. The side effects of the speeding up of the heart rate (which also occur in tobacco smoking, though not to as great a degree) can include temporary change in body temperature, dizziness on standing and diminished capacity for exercise. There is as yet no evidence of heart disease caused by marijuana or any evidence of permanent effects to the hearts of healthy individuals, though Reese T. Jones cautions that, "The lessons learned from chronic tobacco use are worth considering [since] THC seems to have a far more profound effect on the cardiovascular system than does nicotine." Hormonal Effects: ================= Effects from both acute and chronic exposure to cannabis have been shown in laboratory animals. In male animals, the primary effects have been a lower sperm production and changes in the serum testosterone levels in the blood. In female animals, changes include disrupted menstrual cycles and a decrease in the production of prolactin, a hormone which aids in the production of breast milk. In humans, there appears to be a modest reversible suppressive effect on sperm production, which some studies debate, nothing that tolerance quickly develops and sperm production rises again (even during smoking) with no evidence that this has a deleterious effect on male fertility. Female hormonal study, at best, indicates a slight disruption of menstrual cycles. Some researchers are quick to point out that this disruption would have an obvious effect on those trying to conceive on particular days, while others don't feel this is a particularly negative effect. Some scientists feel that for men with marginal procreative or sexual functions, even a slight lowering of their testosterone levels might cause problems - though studies have failed to show this clinically. Scientists across the board are concerned with the possible problems connected with pre-pubescent, chronic smokers and what effect even micro and reversible hormonal changes would have on their development. As yet there is little evidence to suggest any great problems in this area, but there is general agreement that this situation requires further study. Cell and Chromosome Effects: ============================ The numbers and kinds of chromosomes - Structures in a cell nucleus which contain and transmit genetic information carried by DNA - are characteristic for a given species. Structural variation and changes in the numbers of chromosomes may be evidence of genetic damage due to drugs or other cmemical agents. While there have been studies which indicate that tar found in marijuana smoke can inhibit cell division in certain types of cells, there have been fairly conclusive studies made which indicate that marijuana does not break chromosomes. Studied that do indicate chromosomes have either been conducted on lab animals - using doses of THC which were larger than humans could conceivably take - or on multiple drug abusers, and those results "may be due to other factors associated with a life of heavy drug use." The Relman Report - a government-sponsored study of marijuana and health conducted in 1980 to 1981 to review all the then-existing marijuana research - concludes that "the weight of evidence from human studies indicates that neither marijuana nor THC causes chromosome damage." The Immune System ================= The immune system functions in protecting the body against viruses, bacteria, poisons and other infections. It also plays a major role in preventing the growth and dissemination of cancerous cells. The primary components in the system are two active white blood cells (T-cell and B-cell) and macrophages. B-cells identify specific body enemies and produce antibodies to chemically disarm them. T-cells consume viruses, poisons and cancerous cells. The primary job of macrophages is to stop anything breathed in that could cause disease by absorbing it. Both the T-cell and macrophages grow as they consume, and they divide when they have reached their size limit, creating more of themselves. Any inhibition of these functions, either in identification, consumption or creation of antibodies to fight off the invading agents is called an immuno-suppressive effect. The body simply isn't handling the problem. Some early studies in this area indicated that the T-cell's ability to divide was inhibited by THC, though these studies were conducted only in the laboratory. Later studies have shown a weak immuno-suppressive effect in macrophages, though these effects varied from subject to subject and were regarded as transitory. That is, shortly after smoking, while there was a high concentration of THC in the body the body, there was a measurable change; the response returned to normal as THC levels dropped. More recent studies, conducted by Munson and Fehr, conclude that marijuana reduces resistance to infection but acknowledged that this change would very from person to person and would most often by minor: "It is likely that we would not be aware of profound changes in the resistance of humans if they occurred frequently. But even minor effects would be significant among those with immune disorders or with immunity otherwise suppressed." On this last count, there is some concern from several quarters. Even minor changes in immune response have to be looked at critically in the light of the current AIDS epidemic, not as a cause by any stretch of the imagination, but simply because it is an area which has not yet been researched. This is not a cause of concern for the user. It is only mentioned because a number of scientists feel that ANY drug which relates, even mildly, to the immuno-suppressive response cries out for research in view of this new problem. Pregnancy and Offspring ======================= Early reports which tied cannabis use to birth defects in humans on the grand scale - webbed feet, retardation, and so on - have been discounted by even the most anti-cannabis scientists. Those studies that reported these findings generally dealt with lower-economic groups who practiced poor nutrition, drank heavily and were often multiple drug abusers. Even then, such major birth defects showed up with such rarity that few people took them seriously. The reality is that while there are some effects to the offspring of both humans and animals from cannabis use - generally from cannabis use - generally from PURE THC - the changes are not very dramatic. Saraseth, Carol Grace Smith, Susan Dalterio and Peter Fried, among others, have found unhealthy changes in offspring of lab animals exposed to THC, but most of these involved short-term nervous disorders, aberrant visual attention spans, lighter birth weights and shorter gestation periods. Radical doses of THC have had greater effects, but only in lab animals and these did not correspond with human test results. Of the above mentioned researchers, all but Dalterio agreed that offspring whose mothers were exposed to cannabis or THC caught up with non- exposed offspring within thirty days after birth. Dalterio's work deals with second generation mice, and her early results - roundly disputed - suggest that fertility and hormonal production can be affected in those second generational lab mice. Dr. Peter Fried, a leading researcher in the field who works with human offspring, says, "There are no major effects to offspring when marijuana is used in conjunction with good nutrition during pregnancy. Marijuana has been used by middle-class women very comfortably during pregnancy since the 1960's. If there were any major effects they would have been noticed by now. But that doesn't mean that there aren't subtle effects that might be important." Those effects include "a significant increase in symptoms associated with nervous symptom abnormalities which might indicate a mild form of withdrawal...the optimum condition is for a pregnant woman not to use any exogenous agents at all." Because THC is known to cross the placenta and to be found in breast milk, and because the effects - even minor effects - are not fully understood, this sentiment is generally echoed in the scientific community; use of cannabis by pregnant women is not recommended. The Brain ========= Despite two outlandish studies published in the 1970's which concluded that marijuana caused brain atrophy, researchers universally agree that there is no evidence that cannabis causes structural changes in the brain. On the other hand, several teams of researchers have found changes in the brain's electrical activity in human beings during the most active periods of THC action. These changes diminish as the effects of the "high" wear off. More to the point are the chemical changes marijuana causes, since these changes are what produce the "high," and the issue of accumulation. Most researchers agree that while THC in minute doses remains in the brain for some time after smoking, it is neutralized. New studies have found traces of subcortical activity, presumably related to marijuana use and isolated to that use, long after the "high" was worn off. Reese T. Jones had written in 1980, after much study, that "the weight of evidence [indicates] that lasting neuro-physiological impairments are possibly, but not inevitably, associated with some undetermined level of heavy, prolonged marijuana use." Dr. Jones was one of the members of the Relman Committee, and when I spoke with him recently about his 1980 findings he said, "The conclusion of the National Academy of Science group - the Relman Report - was that not all the answers were known but that one should not be complacent and assume you're gonna get away scot-free. They were a very good group of researchers, most of whom had no axe to grind about marijuana. It's a very complicated drug, or series of drugs and there's so much we don't know." Several other scientists I spoke with felt the same way. The brain is very complicated, and the effect of cannabis on it is not fully understood. Subtle changes invisible to testing methods may occur. Gilekson, making a humorous report to a Senate subcommittee in 1980, concluded, "Marijuana may not lead to death, but it might reduce the chronic smoker to mediocrity." Still others are not convinced that there is any evidence to support the idea of accumulated toxicity or any other effects which are not entirely reversible once smoking stops. But even they would like to see more research money spent to study long-term effects to chronic, heavy smokers, and almost no one is willing to commit themslves to saying there are absolutely NO lasting effects, because so much remains to be understood about how the brain really works. No scientists of repute suggested any real hazards in this regard for the casual user. Patterns and Behavioral Syndromes ================================= Although there is no evidence to suggest that a specific cannabis psychosis exists, there has been enough clinical evidence of negative behavioral patterns among chronic cannabis users for researchers to recognize the interaction of the drug with previously existing problems. In other words, psychological problems and psychiatric illnesses, while not necessarily caused by chronic smoking, can certainly be worsened by it, according to Rick Seymour, of the Haight-Ashbury Drug Abuse Clinic. These "long-term problems or situation - where marijuana is being used to self- medicate underlying psychological problems - call for appropriate counseling by health professionals." Frequently discussed behavioral patterns among chronic smokers include: - Antimotivational Syndrome: Characterized by apathy, loss of ambition, loss of effectiveness, diminished ability to carry out long-term plans, difficulty in concentrating and a decline in school and work performance. This syndrome may be seen in non-smokers of marijuana, and even chronic use is not always associated with loss of motivation, but people experiencing these symptoms will, again according to Seymour, "Probably worsen the situation by taking any sedating drug." Biologically, this syndrome does not exist, but, as Hollister, a reputable researcher notes: "One cannot help being impressed by the fact that many promising youngsters change their goals in life drastically after entering the illicit drug culture, usually by way of cannabis. With cannabis, as with most other pleasures, moderation is the key word." The problem, for the user, is to determine the difference between use and abuse. - Toxic Delerium: Also known as acute brain syndrome, it is characterized by a clouding of consciousness manifested by impairment of ability to sustain attention to a goal or stimuli, changes in sleep patterns and sustained disorientation. These symptoms are found only occasionally, and then usually in long-term heavy users. Reese T. Jones has said, "Almost anyone given the right dose in the right setting can be made to exhibit a set of schizophrenic-like symptoms." Symptoms disappear with abstinence, provided there is no additional psychological or physiological problem. - Effects on Pre-existing Mental Illness: Clinical, not biological, evidence suggests that in some cases - particularly patients with mood disorders and schizophrenia - may be negatively affected by smoking grass. -Flashback Syndrome: While there is no biological evidence yet of a flashback syndrome, many researchers feel that there is a king of deja vu - often relating to acute anxiety - that many marijuana users encounter. Mike Wizner of the Beverly Hills Detox Center, says he regularly treats people for these negative feelings, which in some cases can be quite severe whether chemically induced or not. - Affects on Aggression: With the exception of the occasional rare individual with some special disposition to violence, every experiment conducted with cannabis has shown a decrease in aggression in the user. Addiction ========= Most reasearchers agree that addiction, literal and physiological to cannabis can occur after unspecified, long-term, heavy exposure to the drug. But withdrawal symptoms are very mild - slight depression, anxiety, possible nausea - and of very short duration - several days or less. Fear of withdrawal is not seen as a reason for continuing use. On the other hand, "You have the same sort of psychological syndromes you do with any other addiction," according to Dr. Norman Zinberg of Harvard Medical School's Department of Psychiatry. Quantities of cannabis needed to attain addiction are nonspecific (varying from person to person) but because they are known to be high, the casual user does not run the risk of physical addiction. Stepping Stone Syndrome ======================= Marijuana use does not physically lead to the use of, or experimentation with, any other substances. Moreover, government studies indicate that changes in an individual's behavior start before drug use. On the other hand, clinical studies indicate that experimentation with one drug seems to open a gate for experimentation with others. According to the National Institute for Drug Abuse, those people who are going to have drug problems generally begin by drinking alcohol and smoking cigarettes, becoming addicted to one or the other of these substances and then experiment with speed or cocaine. Cannabis and the Drug Addict ============================ Rick Seymour has been working for years with people who have drug related problems and has written extensively for a number of journals and magazines, including High Times. When asked whether marijuana is harmful to addicts trying to stay clean, he says "People who are getting off alcohol or other drugs are in a position of having to deal very carefully with what they are doing with their lives, from their diet to their behavior and so on. What happens when they smoke is that grass creates a sense of euphoria that reminds them of how nice it was to be loaded and there is goes. It's as simple as that. There could even be a physiological factor that we don't know about...[smoking] does seem to contribute to relapses among addicted people." Possible Medical Uses of Marijuana ================================== Various societies have used cannabis to treat a variety of illnesses over the centuries, and Western medicine has recently begun to investigate cannabis as well. According to the Relman Report, there are two reasons for medical interest: The first is that cannabis exerts its effects "through mechanisms that differ from those of other available drugs," and secondly "since cannabis often works as an additive with other drugs, it is possible that cannabis could be combined with other drugs to achieve a therapeutic goal, but with each drug being used at a lower dose than would be required if either were used alone. As a result, fewer side effects would be expected to occur." Some of the experimentation has been promising, but some has been a dismal failure. (Note Rick Seymour's comment about drug addiction in the section on syndromes.) Some of the areas of the therapeutic potential of cannabis include: Glaucoma: Smoking marijuana reduces intraocular pressure in many patients, but the effect is temporary (only as long as three or four hours), and many patients don't like the side effect of intoxication. Some research is continuing with the thought of isolating Delta 8-THC and making a topical ointment that would have the therapeutic effect without the intoxication. Chemotherapy: Vomiting and nausea which accompanies chemotherrapy treatment in cancer patients is so awful that some patients discontinue treatment. Cannabis has been found to be an anti-emetic (anti-vomiting) agent, and Delta 9-THC has been made available through the Food and Drug Administration for this purpose in most states. Again, the intoxicating effects are sometimes disorienting, and the treatment is seen as worse than the disease. Some research is going on in an attempt to isolate certain cannabinoids which would produce the anti-emetic action without side effects. In some cancer patients cannabis has been shown to be an appetite stmulant, but here too, side effects have kept many patients from continuing its use. Anticonvulsant: Human and animal studies have shown that Cannabis can be useful in blocking certain types of seizures - notably certain types of epileptic seizures - and research is being done in this area. Muscle Relaxant: Petro and Ellenberger have demonstrated that cannabis is effective in relieving muscle spasm or spasticity, though there seems to be no evidence of continuing research in this promising field. Asthma Relief: While marijuana works as a bronchodilator and was thought at one time to be of possible use in this area, it is no longer considered viable because of the tolerance that develops to the smoke. Some work is being done on isolating compounds which might be effective and not require smoking. Analgesic Action: While some studies have shown cannabis to be effective in blocking certain types of pain, none show it more effective than what is already on the market. No further research is currently being done in this area. Alcoholism: While at one time it was thought that cannabis might be effective in treating alcoholism, it has now been shown that cannabis and alcohol have an addictive effect on each other and produce undesirable effects in this area. Opiate Withdrawal: Here too, cannabis was at one time thought to be an effective tool. Now, however, it has been shown to not aid the withdrawing addict and to possibly reduce mental toughness, actually leading to continuing addiction and relapse. Cannabis Research ================= 1. There is a problem of relating animal research to human experience. In many areas the crossover is not accepted as accurate. 2. Problems are encountered in regulating the dose. In research it is easier to use isolated Delta 9-THC, though it is rarely used by itself in the individual, and the isolated component doesn't necessarily act the same way when it is found as part of the whole plant. 3. Since researchers are not permitted to take non-smokers and make them smokers - grass being illegal - they must study subjects who already smoke. Since smokers are often multidrug users, assessing what part of a health issue is directly associated with grass is often a difficult and, certainly a manipulable factor. 4. In studied of cross-cultural smokers, ganja smokers in Jamaica for example, critics of these studies point out that the accurate histories of the subjects contain variables that researchers cannot control. Proponents of these cross-cultural studies point out that these populations have a generational history of smoking. Critics point out that in cultures where cannabis is acceptable, it is acceptable only among laborers, not in intelligentsia, and so results are not applicable to our society. 5. Not every researcher is scrupulous, and the lure of a research buck or continuing research bucks for information the funding organizations want to hear cannot be overlooked. Summary ======= Enough is known about the effects of marijuana to keep most researchers from saying that the heavy, chronic smoker will get a completely free ride. There have been demonstrable negative effects to the lungs and unanswered questions regarding several other bodily functions. It's questionable whether these represent a serious danger to the user: The answer you get depends on the researcher you speak with. At this time, the adverse effects appear fully reversible though abstinence, though a good deal more research is hoped for in several areas to clarify the issue. Information in this report was compiled primarily thorough the use of several research review/overview reports. Specific bibliographical requests will be furnished on request. Address queries to Peter Gorman, C/O High Times, 211 E. 43rd St., New York, NY 10017. Marijuana Research/Overview Reports =================================== Dewey, Wm. L., "Cannabinoid Pharmacology," Pharmacological Reviews, Vol. 38, #2 Hollister, Leo, "Health Aspects of Cannabis," Pharmacological Reviews, Vol. 38, #1 Jones, Helen C. and Paul Lovinger, The Marijuana Question, Dodd, Mead, 1986 Latimer, Dean, "The Complete Cannabis," High Times, Feb. 1985 National Institute of Drug Abuse, various reports furnished by the U.S. government. Smith, David, M.D. and Rick Seymour, M.A., "Abuse Folio: Marijuana," a look at the nature, use and hazards of grass; High Times, October, 1982 United States Congressional Subcommittee Hearings, "Health Consequences of Marijuana," 1980 United Sates Department of Health and Human Services, HHS News, May 5, 1987 Unites States Secretary of Health and Human Services/National Institute of Medicine, Marijuana and Health, "The Relman Report," a study of all known marijuana research conducted between 1965 and 1980; National Academy Press, 1982. Wert, Renee, Ph.D. and M. Raulin, Ph.D., "The Chronic Cerebral Effects of Cannabis Use: Neurological Findings," International Journal of Addictions, Vol. 21, #6, pp. 605-628 World Health Organization, reports acquired from the United Nations. Zinberg, Norman, Drugs, Set and Setting, Yale Press, 1984