One often confronts in drug discussions a plea for more and better research before any drastic change is made in existing policies. The idea persists that somehow "research"—if only we had enough of it—will convert difficult policy issues into hard certainties. Its corollary is caution: any permissiveness toward drug users is premature, for later research, as in the case of cigarettes, might show that drug which do not now seem very harmful are indeed deleterious. Rather than risk engraining a possibly harmful practice, a hard-line approach should be kept until all the answers are in.

The prevalence of this idea is easy to document. Westerners have difficulty denying the authority of scientific findings. Also, one can agree that marijuana, LSD, etc., are not as bad as commonly thought, but still consistently resist changing existing laws. The New York Times, February 13, 1971, stressed the "desperate need for further research" in commending the call of a legislative commission for marijuana reform that would fall short of legalization. The editors of the Boston Globe,' after running a five-day in-depth analysis of marijuana,2 refused to endorse the conclusion that marijuana should be legalized on the ground that all the facts were not yet in. The Secretary of HEW, in a report to Congress entitled "Marijuana and Health," cites "the many unanswered questions" about marijuana as preventing a "final verdict" on policy and concludes that "until we know more about the drug we certainly can't give it a clean bill of health."

Certainly the psychopharmacology of psychoactive drugs leaves much to be desired by way of hard knowledge in several important areas, particularly about long-term effects. The idea, however, that research will answer these questions, and then also decide the hard social and political decisions ahead, illustrates a pervasive misconception at the very heart of the drug issue. The misconception is that we must be able to give a drug a clean bill of health—a "final verdict"—before we stop criminalizing people who use it, and further that research can technically provide that answer.

The we-don't-know-enough-now argument is deficient in several respects. Perhaps the most important is its confusion between harmfulness and legality. Even if all the evidence were in, the question of whether personal use and possession of a drug should be criminal would still be open. While this subtlety has not been missed in the case of cigarette smoking, most people have great difficulty in separating the two questions where other drugs are concerned.

The more-research-before-change posture also assumes that given a little more time, modern science can come up with the desired answers. In a world where the obstacles to definitive research described later in this chapter did not exist, this argument would still be unconvincing. Usually it is lack of knowledge of longterm social, psychological, and physical effects that is used as a basis for caution. Yet it is precisely knowledge of those effects that is out of reach at the moment. Indeed, if ever we can with assurance pinpoint the long-term effects of drugs, it will be a generation too late to resolve the dilemma now confronting us.

Finally, the proponents of caution tend to overlook the vast body of knowledge concerning the effects both of drugs and of the laws regulating them that now exists. Thousand of years of opiate, cannabis, and hallucinogen use have left us with considerable, albeit rough, knowledge about their effects. A surge of research and increased knowledge in the past thirty years enables us to say some important, if not definitive, things about drugs. Even more important, over fifty years of experience with police control of drug use has demonstrated the ill effects of an unbalanced, overly moralistic approach. Although we cannot scientifically assert that marijuana smokers some thirty years from now might contract some unknown ill, we do know that the drug laws are ineffective, costly, unjust, and unnecessary in dealing with problems of drug misuse.

In a time of burning conflict over drugs, the demand for more research seems less a desire for knowledge than a ploy to maintain a particular position. In an important sense it becomes a diversionary tactic that absolves legislators and the police from rectifying past errors. The recently appointed National Commission on Marijuana and Drug Abuse demonstrates quite clearly how the call for more research is used to avoid difficult political choices. The commission is to report on the extent, type, and nature of use, give an evaluation of the efficacy of existing laws, study the immediate and long-term effects and their relationship to aggressive behavior, crime, and other drugs. From numerous reports and blue-ribbon commissions, ranging from the Indian Hemp Commission of 1893-94 to the 1969 Wootton and 1970 LeDain Report, most of these questions have been answered. Nor is a national commission needed to determine the "efficacy of the law"—most people are by now aware that it deters hardly anyone. One is justifiably skeptical when a national commission and a million dollars are needed to answer questions to which people already know the answers. Indeed, other purposes may be discerned in this enterprise. While state and national pressure for change is mounting, the existence of a commission adroitly puts off legal change until its recommendations are in. And, as experience with the Kerner, Scranton, and Obscenity commissions shows, there is no guarantee that what any commission concludes will become law. The call for research is a holding action, a desperate lunge for reassurance, in the hope that final proof that "we were right" will be forthcoming or, at least, will postpone the recognition that we were wrong.

There are other grounds for suspecting the call for more research. Given the nature of drugs and the legal and financial controls that exist over research, we doubt that research will definitively answer the currently unanswered questions. Throughout this book we argue that the base of any legal controls over drug use is general social and psychological acceptance of limits It is not that basic research in a whole variety of areas is of little use, but the view that research will help us with the crucial issue of social control and the irrationality that pervades our feelings about drugs is fallacious.

In this chapter we will indicate three reasons why research in this field is difficult: (1 ) the illegality itself, (2) the moral position from which research is undertaken, and ( 3 ) that set and setting, more than the drug, determine the response to psychoaffective drugs in humans. Research, broadly considered, may comprise investigating the mechanism of the drug and the body (physiological, biochemical, or pharmacological), studying the response of the person (psychological), and determining changes in attitudes or-behavior of the population as a whole (sociological).

ILLEGALITY

The illegality of drugs ensures that only researchers who are sufficiently dedicated to spend months continuously on the phone or in correspondence with more than a dozen different agencies will get under way.

One of the authors who participated in a research project3 in which marijuana was given to human subjects experienced the difficulties firsthand. In order to do the research it was necessary to get official and explicit clearance from the FDA, NIMH, Federal Bureau of Narcotics, Massachusetts Division of Dangerous Drugs, Attorney General of Massachusetts, local police officials of the district in which the research was to be carried out, the local district attorney, the executive committee of a medical school, a research committee of a medical school, a public information committee of a medical school, a dean's office, a research committee of each university whose newspaper carried advertisements for subjects, medical departments of various universities, and several professors of departments whose specialties might be touched on by this interdisciplinary work. It was not just that these different people needed to be contacted, but in addition, each read, criticized, and requested changes in the research proposal. Several felt that their regulations concerning such research conflicted with the rules of another agency. For instance, once the Federal Bureau of Narcotics, after months of effort, licensed the investigators, agreed to refrain from prosecution of subjects, and supplied the marijuana, the NIMH questioned this permission because the research was not sponsored and funded by them.

One medical school, after months of committee meetings and numerous appearances by the investigators, declined to approve the project because it called for giving marijuana to naive subjects, and the committee on research feared that it might begin an addiction. The committee advised omitting this key part of the research and permitting only chronic users to participate. When the research was moved to another university, a professor of a related department attempted to block the project unless it was under his complete control so that he could be sure it followed the principles of his discipline.

The Attorney General of Massachusetts, after giving the project his personal approval, found that he had no legal right to exempt research subjects who had performed an illegal act from the consequences of that act. This presented a stumbling block for the local pouce and legal officials who did not want to interfere but who also did not want to appear to condone dangerous illicit acts.

The legal department of one medical school objected to the permission agreement signed by subjects drawn up by the legal adviser of another medical school. The latter had been hired separately because the official legal counsel of that medical school had told one investigator that he had found no legal reason why this research could not take place, but had searched his conscience and decided this work to be morally objectionable and would advise the medical school against participation. The legal department of a second medical school wanted someone to drive the subjects home after the experiments, to ask them to refrain from touching any electrical or mechanical equipment for twelve hours after smoking the drug, and to require an individual to stay with the subjects for 24 hours to be sure there were no untoward physiological or psychological reactions.

Originally the Federal Bureau of Narcotics indicated that they would give the special license to possess marijuana to a physician only if he were a qualified investigator in the field. It was the old "can't hire anyone to work without experience, and thus can't get experience if you can't get a job" bind, because without a license one could not be an investigator.

There were literally hundreds of such incidents requiring unlimited time and unending patience. The experiments finally took place only because Dr. Andrew Weil, one of the investigators, was a senior medical student at the time and had made this his senior project. His backing, together with that of Drs. Peter Knapp and Conan Kornetsky, opened several previously immovable doors and at the last possible minute, the word was go.

The experiments themselves went smoothly. The findings showed little about acute intoxication with marijuana that could be considered troublesome, but many colleagues of the investigators roundly condemned them for publishing such findings, complaining that they incited others, particularly youths, to break the law. There were comments and letters to Science,4 Namre,6 and The New York Times6 sharply questioning the right to perform such research, the intrinsic motives of the researchers, and implied judgments. This book abounds with examples of the fact that drug use is seen as a moral issue, so it should have come as no surprise to find that this is equally true in research. It is a matter of some moment, however, because of the nature of research itself.

MORAL POSITION

Research on drug use departs from the tradition of objective study and embraces the moral position that nonmedical drug use is wrong. To many investigators it is no contradiction to attempt research on the basis that drug use is wrong. The idea has been to discover what proves nonmedical drug use wrong and to "educate" the public to these findings so that drug users will cease and desist. It is a minor scientific scandal that the researchers who found that LSD causes chromosomal damage started out with the premise that LSD was obviously worse than people thought. They decided on this research in order to find out what made it so bad and to disseminate this to the public as soon as possible in order to stop more people from using LSD.7

A report of November, 1969, issued by the National Institute of Mental Health8 describes all the programs funded by them on drugs. Since this report was issued, the new director of NIMH, Dr. Bertram Brown, has sharply revised the organization's position in a 1970 report entitled, "Marihuana and Health, A Report to the Congress from the Secretary of Health, Education and Welfare" (January 31, 1971).

The later report still declines to answer the question by calling for more research before public policy changes but sharply avoids the moral tone of the special report in 1969, "Drug Abuse." It begins by delineating certain recent trends, the first of which is "the misuse of drugs is not limited to this country." The beginning of the second trend is "the abuse of narcotics, sedatives and stimulants continues to increase."10 At no point in the report is there any proof that drugs were misused specifically in other countries.

In part four of the report, "Narcotics," the researchers comment on the fact that the Bureau of Narcotics and Dangerous Drugs"- reported the number of addicts in the United States as 64,000 as of December, 1968. The figure of approximately 60,00012 was used in 1952, before the passage of the Boggs Act. From 1952, then, to 1968, there was no indication of any change in the essential number of addicts in the United States. Far from proving an increase in use and abuse, the report presents a figure that would indicate the opposite in light of the increase in population during that period. They write: "A most important aspect of the National Institute of Mental Health's mission is to mount needed programs to deal flexibly with the many facets of drug abuse. As the problem is complex and changing so must be the strategies designed to understand and to cope with it."" An official government bureau intends to proceed with an action program to cope with a problem for and against which they have no scientific evidence.

We have consolidated all elements playing a role in the area of drug abuse into a single division, The Division of Narcotic Addiction and Drug Abuse. This consolidation permits a more rapid translation of the results of research into treatment practices, and in the opposite direction emerging problems in treatment or education can be quickly identified and researched.14

That this is an action-oriented program to fight or clear a present evil can be read in almost every page of this report, even though ostensibly the report is committed merely to comment on the activities of the largest organization involved in funding research on drugs in the world.

SET AND SETTING

In studying the psychoactive drugs a researcher can obtain information by actually giving a drug to subjects in a laboratory and watching what happens. He can ask users what effects they get from the drug. He can give the drug to animals; he can study the drug's action in vitro by devising a series of experiments. He can also study various body tissues and fluids to gain some understanding of the further breakdown of the drug once it is in the body. Actual follow-up of the breakdown of the chemical components of the drug in the body is obviously of great value in determining its elimination. However, none of the foregoing techniques tells us very much about the psychological affects of drugs and their effect on people's behavior and attitudes. Although a drug given to animals may tell us a great deal about toxic doses and invariant pharmacological actions, the translation of animal responses to human responses has not been so useful when connected to substances whose chief property is psychoactivity. The most important thing we have learned about drugs that affect the mind is that the pharmacological action of the drug in vitro or in animals is but one of three factors that determine how a given person will react to that drug on a given occasion. The other factors are set and setting. They are at least as important as the reaction of the drug itself unless the drug is given in toxic doses. Set is the psychologist's term for an individual's expectation of what a drug will do to him. It includes much of what we commonly call "personality." Setting is the total physical and social environment in which the drug is taken.15

It is quite possible for the combined effects of set and setting to completely overshadow the pharmacological action of a drug. Thus, a barbiturate that pharmacological texts tell us is a "sedative" can produce stimulation under certain set and setting conditions. Influence of set and setting is so profound that even drugs that we customarily think of as producing consistent physiological responses, such as digitalis and atropine, under certain conditions of set and setting can become stimulants or provoke anxiety reactions. These responses can be sufficiently unpredictable to make physicians careful in their initial administration of even such medically tried and true substances.

The more the drug can be considered psychoactive (in that a principal -reason for ingesting the substance relates to desired changes in mood, emotion, perceptions), the more set and setting are crucial. When obtaining information about drugs it is hard to measure the importance of set and setting. Hence, the kind of information that might be obtained by questioning users may well be grossly unreliable. What each person may say will apply subjectively to him, but whether it is pharmacologically accurate and can be applied to other persons is never clear.

Nearly all the collected scientific literature on psychoactive drugs consists of this kind of information. It is a collection of rumor, anecdote and secondhand accounts. This is best exemplified by a recent comprehensive study of marijuana by Lester Grinspoon.16 Nearly half the book is given over to culling the literature and statements of people from Le Club des Hachichins» Ludlow,18 Baudelaire,19 DeOuincey,2° Ellis,21 Leary,22 and others. When reading these charming and highly literate descriptions, many of which contradict each other, it becomes obvious not only that the statements are individualistic and idiosyncratic but that much of what is recounted has been gathered from countries where set and setting are drastically different from set and setting in an American college community or Bedford-Stuyvesant.

This is not to say that experimental, laboratory information is always "right" and information from users is always "wrong." In fact, laboratory information has equivalent problems. The essence of the experimental method is manipulation of the environment so that an observed effect may be ascribed with some confidence to a known cause (in this case, the administration of a drug). When set and setting are more influential in determining the experimental response than the drug, and those factors- are unmeasurable and cannot be held constant, then the experimentalist must either guess at their effect (virtual blasphemy) or reduce his experimental field to so small a point that his results mean very little to anyone.

Consider a simple example. About nine out of any ten marijuana users we have interviewed have told us they are certain marijuana dilates the pupils of their eyes when they are high. An even higher percentage of law-enforcement agents have told us the same thing. But pupil size depends on other things besides what drug you may happen to have inside you. One obvious determinant is the surrounding illumination: dim light in a room in which one's eyes are focused will cause pupil dilation as part of the eye's accommodation for near vision.

Therefore, if a researcher wishes to measure the effect of a drug on pupil size, he is obliged to hold the other factors constant—to control them. He must measure the pupils before and after administration of the drug under constant, standard illumination with the eyes focused at a constant, standard distance.

Observations made by users or law-enforcement agents at pot parties are not likely to be this scrupulous. When Weil and Zinberg finally did an appropriate experiment in Boston,23 they were not surprised to find that pupil size was not changed at all by marijuana. (Since the lighting at marijuana parties is often dimmer than usual, it is also not surprising the participants commonly have large pupils.)

The curious problem of the experimentalist, however, is that as he controls the laboratory environment more and more carefully in order to maximize his confidence in ascribing observed effects to known causes, his laboratory becomes less and less like the real world, which is what he set out to study. Indeed, control can proceed to the point that the experimental results are scientifically impeccable, but their relevance to anything in the real world is lost. Then, if someone comes along and says, "So what?"—as happens all too infrequently in science—the experimentalist will be stuck for an answer.

An article by A. J. Mandell and C. E. Spooner in Science, called "Psychochemical Research Studies in Man,"24 attempts a definitive criticism of general research strategies. They point out that such strategies in science, despite attempts at objectivity, are often dictated by conceptual models that hold transitory sway and pass on. The attempt to understand brain function and behavior in terms of chemical events in the central nervous system may be just such a faddish "paradigm."

The authors review four leading research strategies and find them all wanting. They point out first that experiments on animals with drugs that affect human behavior look for neurochemical correlates of drug action. The problem with this approach—whenever it is tried and however carefully it is used—is that one is left with correlates of action with no obvious connection to real behavior.

When they next talk about a research strategy to give humans large doses of compounds that are thought to be precursors of behaviorally active substances in order to watch for behavioral change, the authors describe the nonspecificity of such an approach. One has no way of knowing what did cause the effect if a behavioral change should occur. Was the effect caused by the precursors' metabolism into an active compound, or did intermediates of the metabolic pathways become active? Or were the behavioral effects a consequence of a general metabolic derangement caused by an initial, large dose of the precursor?

Sleep-stage specificity, the third strategy discussed, refers to the use of sleep stages as a dependent variable to test drug effects. This approach makes it possible to have a constant across a number of species. Different chemicals produce the same electrophysiological state. However, here too, while we have a constant, sleep, which makes for neat research, we cannot obtain specific correlates between chemistry and behavior. And, finally, when one searches for metabolic errors that result simultaneously in derangements of chemistry and behavior, it is not possible to relate the chemical abnormality to specific changes in brain function or specific changes in behavior.

The authors recommend a fourth strategy: a regulatory model in which body functions are end results of complex interactions of regulatory systems that can respond in a graded fashion to .external changes. Longitudinal studies on individual subjects in which chemical changes are monitored over a long time period are intended to determine correlation with behavior but would leave correlates, not causes. The data in this method become as confusing as the rest if we try to force a specific cause-and-effect relationship on them. The nonspecificity problem is inherent in any model that attempts to make physical events more determining or basic than mental events.

Very few people, scientists or users, would disagree about the extent of the influence of set and setting on the response to a psychoaffective drug. And yet many people continue to act as if this intellectual agreement had very little to do with developing social policy. They behave as if that were somehow irrelevant and look to science. The essence of science lies in our ability to describe, predict, and explain phenomena. Our chemical and pharmacological knowledge of drug use does not fit these criteria. These approaches can teach us much about the drug itself and much about the changes the drug causes in our bodies. All of this is important, and could in time influence our thinking, balanced with a number of other social and psychological considerations such as social rituals, civil liberties, and pleasure.

It is clear now that science can tell us nothing about why a morphine addict says he gets a "rush" from his shot when he takes it in a deserted pad in the South End but, when given the same shot in the antiseptic ward of a modern general hospital, feels little or no pleasure. What light does research cast on the experience of passing a joint around among friends while listening to music? Has any research method, psychological or otherwise, become sensitive enough to weigh and measure the desire to look at lights and shade and shadow when on a trip or, more mundanely but no more available to experimental rigor, the desire for good cheer and good fellowship and very often song that comes with a few beers. The form that the impulse to get high takes may vary from culture to culture and from drug to drug, but it seems to be a fairly consistent human need.

Reports of users, while more lyrical and more literate than scientific papers, are equally inconclusive as a means of formulating public policy. Certainly the survey research done by B1um25 and others conveys by sheer numbers the knowledge that people who use a drug find it simply pleasurable. However, even here it is so hard to know what people are talking about; the margin for error is great when we consider questionnaires in rigorous research terms.

Laboratory experiments tell us a great deal about what the possibilities are but give little help in predicting an individual's specific reaction in the real world. Until we can account for set and setting in a coherent way, neither the subjective experiences nor the objective physiology will provide data sufficient to determine a rational policy in the face of increasing drug use.

The most important funding agency in the world in drug research is the National Institute of Mental Health in Washington. The research that they were supporting at the end of 1969 certainly exemplifies the leading trends in the field, and we will lean heavily on their report in order to obtain our overview of the area.26

1. MARIJUANA

It is worth noting that of the twenty-five marijuana research projects the NIMH reports it was supporting at the end of 1969 only one could be considered frankly psychological and directly concerned with the response of the person. This project attempts to determine the crucial decision-making points with regard to marijuana and other drugs and draws from a diverse group of subjects. The aim of that research is to determine whether a chronic user of marijuana encounters psychological problems. Decision-making points determine whether he uses marijuana to escape life or stress, and are an attempt at finding whether his mental growth may be impaired by not knowing how to deal with frustration and other problems. The study further tries to decide whether a user may drop out of active involvement in school or work. The moral bias of this research seems unquestioned. It begins with the premise that the use of marijuana is a crisis decision and indicates by the way that the proposal is stated that marijuana use is seen as an escape. The research questions this social pathway to determine not whether but how it interferes with the user's following a "better" way of life.

Six listed projects fall under the general heading of sociological. These are surveys of the extent of drug use and questionnaires to determine the characteristics of users. Most deal with the use of drugs other than marijuana.

Other funded sociological research is intended to determine something about the marijuana user, and it does look at the relationship of marijuana use and other drugs, the question of how much people smoke, the correlation of their political principles with marijuana use, the relationship of their sexual practices to marijuana use, and their views of patriotism. Generally speaking, these studies point to where the marijuana user can be placed on the conservative-liberal-radical dimension in a number of areas of psycho-socio-political life. However, none of the studies funded by NIMH pays any attention to the relationship of setting to the development of these attitudes and views on the part of the user. One expensive study puts marijuana users and alcohol users together in a group and has the rather impressive finding that observers could distinguish subjects who were high on marijuana from subjects who were high on alcohol.

The remainder of the studies but one were interested in experimenting with the ways of separating tetrahydrocannabinol (THC) by liquid chromatography or through an extract by a red oil method which will separate as much of the noncannabinol types of material as possible without destroying the THC content. There is a metabolic study of cannabinol compounds in marijuana, as well as a variety of biosynthetic methods to detect the remnants of marijuana in body fluids as well as in biological tissues.

Two of the studies are intended to try to find the remnants of isolated THC in body molecules. The more explicitly described of these two concludes sadly that the degree of metabolic change may depend more on the amount and purity of the material subjected to the smoking procedure than on the measurement of THC itself.

There is at least one study that will indicate the effect of marijuana on blood levels and urinary excretion and will correlate some Of the results (with human subjects) with motor skills and conventional psychometric testing. The larger studies seem to be on animals and investigate the effect of ingestion in rats and guinea pigs. Particular attention is paid to the effect on fertility with rats, hamsters, mice, and rabbits.

One research project attempts to separate two principles considered active in marijuana. The investigators plan to subject as many animals as possible to the two compounds. Tetrahydrocannabinol will be run through a general central nervous system screening procedure using psychological test procedures and electrophysiological techniques. These will measure things such as motor activity, interaction with alcohol, barbiturates, and amphetaminelike properties. Procedures will be conducted such as self-stimulation reciprocal conditioning and the effect of THC on visual and auditory thresholds in these animals.

Some of the studies have ingeniously worked out ways in which a respirator can be hooked up to a cigarette so that a dog will get some marijuana content through smoking. Electroencephalographic changes are being studied with great care in a variety of animals. None of these studies can take into account set or setting or give any clear indication as to the relationship between what is learned from animals and the real-life situation. There is no reason that this form of research cannot provide highly specific knowledge on drugs which would otherwise be gained through clinical trials on humans. On the other hand, given the moral bias of the research, as indicated earlier, along with this lack of real-world practicality, it is hard to imagine what information will help to make the difficult social-policy decisions.

One other marijuana project funded by the NIMH is a 'strictly applied project. The grant permitted publication of an empirical study of the marijuana law-enforcement administration policies in Los Angeles County. Law students randomly selected cases from the 1966 file of the Los Angeles District Attorney's office and the Juvenile Court and interviewed representative members of the police force, the DA's office, and so on. They found that an officer may spend up to eight hours arresting and booking a suspect and then appearing in court to testify: time, the researchers point out, diverted away from discovering and preventing crimes against persons and property. They also found that 72 to 80 percent of the marijuana in Los Angeles County is shipped to Los Angeles by a group of separate, loosely knit syndicates. They found that the use of informants and undercover agents is effective in discovering violators but makes little headway in halting the spreading use of marijuana. When faced with the alternative of a felony conviction or acquittal, a significant number of judges have chosen to acquit the educated, middle-class user without prior record who, except for his marijuana activities, appears to be law-abiding.

NIMH is doing one other thing that will be of value for researchers. They are funding the growing of marijuana in Mississippi so that the plants used and even the THC separated will be fairly standardized. Thus, researchers in the future will have a clearer idea of what they are working with.

With the range of research just listed, one might assume the field was being well covered by this agency. However, a review of recent marijuana research published by Dr. Charles Gordetzky,27 director of the Section on Drug Metabolism and Kinetics at the NIMH Addiction Research Center in Lexington, Kentucky, takes a different view. There are probably few people in a better position to assess research than Dr. Gordetzky, not only because of his official position in NIMH research, but because he has collaborated with Isbe1129 on basic THC work. Gordetzky questions how difficult it will be to standardize a sample of marijuana that will help with information about other strains because "the amount of resin found in different plants varies so widely with such factors as the climatic conditions under which the plant is grown, and the variation in the geographical area in which it is grown."29 His assessment of THC studies: "For example, we are still not sure if delta-9-THC is the only active principle. The relationships between oral ingestion of THC or smoked tobacco cigarette injected with known amounts of THC and a smoked marijuana cigarette which has been assayed for THC has still not been fully defined."30 He goes on to say:

There are discrepancies between effects observed from smoking marijuana cigarettes which are assayed for THC and those which we would expect from experiments with similar amounts of THC being injected into a tobacco cigarette. With regard to smoking versus oral potency, it may be that the passage of THC initially through the liver after ingestion may produce metabolic changes in the drug which are not seen when THC is smoked and some can get to the brain without passing through the liver. It is also possible that during combustion new products are formed and there also may be some interaction between the components of marijuana not seen between THC and tobacco or vice versa.

. . You may notice that I have continually said marijuana assayed for THC rather than marijuana of known THC content. This is purposeful since some question has recently been raised regarding the accuracy of the assaying done on marijuana used in some reported studies.31,32

He goes over studies that try to relate THC content to extremely unpleasant toxic or even psychotic reactions. He concludes that it is likely that this represents idiosyncratic reaction and not a dose-related toxicity of the drug.

Many of the sociological studies backed by NIMH are geared to indicate whether marijuana leads to other drug use, and the relationship between frequency of marijuana use and other drugs. Dr. Gordetzky,33 in his discussion of this form of research, goes on to say this:

Opponents of marijuana frequently argue that its use inevitably leads to other drugs, for example, heroin. This argument probably begins with a perversion of the appropriately determined statistics that most heroin users began on marijuana. Reversal of this statistic is certainly not logically justified and is in fact probably far from the true situation.

He concludes his comments on marijuana:

You can see that our present state of knowledge is still incomplete and a great deal of work needs to be done before any definitive statements regarding such areas as absolute and relative safety can be determined.

Would the result of such careful work as that of Dr. Gordetzky lead us to believe that we should put off any decisions regarding changes of the law until such information as research has to offer will be available? Dr. Gordetzky clearly takes a dim view of much of the research work that has been done so far, and many of his statements indicate that we can expect little from any of the projects now backed by the NIMH. Another indication of this view is some work done under the supervision of Dr. John C. Krantz at the Maryland Psychiatric Research Center.34

We do not know what the positive aspect of the new work will be; however, the negative implications are of importance. The findings of Krantz et al. indicate that it is impossible to treat THC as if it were the only active ingredient of marijuana. It becomes clear that the cannabinols which were previously considered inactive can be active in either potentiating or blocking the effects of other ingredients. This throws great question on the work of any investigators dealing with a fraction of marijuana which they consider the principal active ingredients, not just because there may be other active ingredients, but because it may be the interaction among ingredients that determines activity. Berger's work lends credence to the view that there are a number of factors in the marijuana preparation which not only act to potentiate each other but may act to inhibit each other and may be of different intensities in different samples.

This work also has important implications for the difference between smoking and the oral ingestion of marijuana. Isbell's work with Gordetzky maintains that THC injected into a tobacco cigarette and smoked is about three times as potent as THC taken orally on a milligram-for-milligram basis.35 This finding has been unscientifically disputed by a number of users. The indication that even the most careful investigators fall into the error of accepting a scientific premise simply because there is "experimental" evidence can be shown by Grinspoon's interest" in this. He quotes Walton,37 who says that cannabis taken orally is more "abrupt" in the onset of its effects than cannabis smoked. Grinspoon goes on to say, "He [Walton] does not mean that the oral route increases the potency or if he does he is mistaken as Isbell et al. have shown."38

Many users indicate that at times oral ingestion is more potent than the smoked route and also say that the effects are qualitatively different. These again are matters about which we know little or nothing.

One could go on detailing the contradiction that comes from supposedly scientific reports on marijuana. The American Medical Association" noted that after the administration of cannabis the "sensation of pain is distinctly lessened or entirely absent and the sense of touch is less acute than normal." However, Allentuck and Bowman" report that there is "increased sensitivity to touch, pressure, and pain stimuli."

What one is left with, when a survey is taken of attempts to treat marijuana experimentally solely as a research problem and to remove it in any way from the human situation, is that one finds that the data are contradictory and that, unless one becomes comprehensively involved in concepts of set and setting, then very little sense can be made out of the data. It is not that researchers have not attempted to go into the more subjective aspects. There has been research on the contention that marijuana use increases one's sensitivity to music. One result reported in Life magazine-relates, ". . . the swinging musician ascends to new heights of virtuosity," when high on marijuana. Walton42 came to exactly the opposite conviction. He says, "There is very little probability that a musician's performance is in any degree improved over that of his best capabilities. As judged by objectively critical means, the standards of performance are no doubt lowered." But Winick,43 who has been one of the leading observers of the drug scene for a number of years, has his doubts. He points out that Walton's study failed to demonstrate enhanced musical ability:

. . . a test in which non-musicians are given objective questions on matters like the consonance of pitch between two sounds, can hardly be compared to the musical creativity and expertise required of the jazz musician playing in a group situation which is based on mutual reinforcement and in which improvisation may be extremely important.

He concluded that the jury was still very much out on that highly subjective question.

2. HALLUCINOGENS

One of the seventeen projects funded by the NIMH44 on hallucinogens is a large survey report that indicates a decreased use of LSD. This finding is directly contradicted by Gallup polls,45 the most recent of which indicates that 14 percent of all those under age 25 now have joined the "have used" category. At the time of the NIMH report they contended that the "have used" category had dropped from a high of 10 percent down to a low of 6 percent. Our interviews indicate a gradual increase of use of LSD with the implication that one might not notice it so much because use has become more private and less connected with total change in lifestyle. Our subjects have reported that LSD is one of the things that people of this generation simply plan to do, and it is not considered necessarily an aberration or a desire to join a commune or a hippie way of life. There have been consistent reports of decreased use ever since the original chromosome papers were published in 1967. These reports probably represent wishful thinking rather than accuracy of the samples.

Most projects funded by NIMH" are biological and biochemical. They study peyote fractions by going back to the direct biochemistry of mescalines and related alkaloids to determine the prototype of the hallucinogens. There is an attempt to study the chemical components of the cactus seed to determine peyote's major biosynthetic pathway. In one project, the synthesis in the central nervous system is studied through drug-treated animals. The Texas Research Institute of Mental Science is studying the effects of twenty substituted phenylethylamines in disrupting animal behavior. Identification of the hallucinogenic activity of unknown chemical compounds is the aim of another project.

The preoccupation with chromosomes continues. Four projects study chromosomal changes in rats and mice, another in schizophrenic children who had been treated with LSD between 1961 and 1966 before "the damaging effects of LSD to chromosomes had been reported."

One psychosocial research project attempts to distinguish those research subjects who were exposed to LSD during the 1959-65 research (before the drug was taken up for pleasure) and sought out the drug later from those who did not. A little more than 25 percent of the group of experimental subjects in those original studies took LSD illicitly after their legitimate exposure. An attempt is made to divide, on a personality basis, the continuers from the noncontinuers. Other studies are intended to show the changes in value systems and career patterns of psychedelic-drug users. Another is concerned with the legal significance of hallucinogenic-drug research, and yet another attempts to show the relationship of hallucinogens to the development of a poly-drug scene. The data from this last study are directly contradicted by data reported from yet another study that indicates that the speed freak and the LSD user have quite a different set of motivations for drug use and in fact get on very poorly together. One project intended to study hippies and non-hippies from New York City's East Village and the YMCA centers in New York define their program as one that should provide some information on which to base a program of preventative activities in the various Y centers.

One applied program sets up a "community" organization in which youths are members rather than patients and serves as a locus of free-time activity in order to help the community meet the various needs of teen-agers. One result of this report is that the NIMH did fund a conference of leading researchers in September 1967. One of the findings was that those attending agrned "that evidence of persisting psychological effects from long-term use of LSD was minimal." Despite this finding the NIMH report continues to refer to the taking of LSD as a problem:

 . . researchers demonstrated the possibility that a mind-shaking drug like LSD precipitates prolonged anxieties, depressive state and psychotic reaction. This has been amply confirmed by clinicians. In addition those who use the drug ostensibly were eventually impressed by the "bum trips" and "flashbacks" that could occur unpredictably.

Certainly the data produced by the conference sponsored by the NIMH do not confirm those statements quoted from the introduction to their description of LSD research actually funded by the agency.

There is currently no research funded that attempts to explain the effect of hallucinogens on consciousness and explore the interesting fact reported by Dr. Gordetzky47 that tolerance is so rapid that regular consumption is impractical. (People develop tolerance quickly and lose it just as quickly.) Dr. Gordetzky has many doubts concerning the research that has found increased chromosomal breaks with LSD. He says, "questions of technique, control groups, sample size, normal levels of chromosomal breaks and the possible effects of other currently used drugs have all been raised"" about research that has shown such breaks. He concludes that there is no reason to feel at this time that LSD is specifically involved.

3. STIMULANTS

Research of the stimulants (xanthines, such as caffeine, theobromine and theophylline cocaine, and a large number of sympathomimetics) suffers from the much-quoted report and mistake on the general effects of cocaine by Sigmund Freud. In 1885 Freud published a highly enthusiastic report on the effects of cocaine.49 He remarked, "A writer who for weeks before had been incapable of any literary production was able to work for 14 hours without interruption after taking 0.1 grams of cocaine hydrochloride."50 Heighténed functional capacity appeared much more regularly as a symptom of the action of cocaine. Part of Freud's research was the rigorous testing of the effect of cocaine on muscular response, and he found that "ingestion of 0.4 grams of cocaine hydrochloride increases the effective work of one hand by two or three kilograms."51 In the same article, he goes on to praise cocaine as an effective antagonist to morphine. A person who had presented the most severe manifestations of collapse at the time of an earlier withdrawal (from morphine) now remained able, with the aid of cocaine, to work and to stay out of bed and was reminded of his abstinence only by shivering, diarrhea, and occasional craving for morphine. "No cocaine habituation set in; on the contrary, an increasing antithesis to the use of cocaine was unmistakenly evident," he goes on to say. "I have no hesitation in recommending the administration of cocaine for such withdrawal cures in subcutaneous injections of 0.03 to 0.05 grams per dose, without any fear of increasing the dose."52

As we now know, cocaine turned out to be a much more complex drug than Freud believed it to be at the time. His enthusiasm in this matter may have affected the entire course of drug research. At numerous scientific meetings, when someone has reported on a positive effect of a psychoactive drug, a discussant invariably recounts Freud's early enthusiasm and later disillusionment. Although some form of cocaine had been known in Europe since the time the Spaniards returned from the initial conquest of South America and brought coca leaves back with them, there is no record of specific findings until 1883 when Dr. Von Assenbront reported that the Bavarian soldiers overcame fatigue and exposure after receiving small amounts of cocaine hydrochloride.53

Amphetamine itself was first prepared in 1887 and methamphetamine in 1927. The drugs were in general medical usage between 1930 and 1960 without arousing much concern. The recent preoccupation with speed freaks—the nonmedical usage—has led to much interest in research in the stimulants, which is now taking place. This is in spite of the fact that there was considerable concern about medical usage earlier and questions as to how dangerous a drug the amphetamines were. At the end of 1969 the NIMH was funding eight research projects which were all or in part related to the amphetamines.54 As some of them were comparative research with other drugs, particularly the barbiturates, they do not stand on their own. In these projects, animals—geese, rats, dogs, mice, hamsters, and pigs—are being studied. These animals are being watched to determine if there is a persistence of drug-taking behavior after the removal of conflict or after brain stimulation; also investigated are the questions of self-administration and methods of self-administration, various aspects of physical and psychological dependency (again as noted by self-administration), neurophysiological concomitants of chronic amphetamine intoxication, the effects directly on the central nervous system (although the relationship between the central nervous system of chicks and that of humans is not directly reported on), and the question of hypersusceptibility to subsequent doses following enhanced response level, as well as the impact of the amphetamines on pregnancy in mice.

Another project obtains urine samples from two human populations, acute psychiatric inpatients and university infirmary inpatients, to see if a chemical detection method for the presence of ten widely used stimulants and appetite-depressant drugs can be developed. The study is intended to discover whether the occurrence of unsuspected stimulant drug abuse is found in a psychiatric population and to provide preliminary information regarding the incidence of stimulant drug abuse in college students.

In contrast to all the other classes of drugs, amphetamines are the one group of drugs that clinical research indicates does result in impulsive and violent behavior. Wei155 contends that this is consistent with their pharmacological instability. He states:

Amphetamine dependency is more serious than narcotic dependency because it is inherently less stable. When a person begins using a tolerance-producing drug, he must soon face the problem of trying to stabilize his use in order to keep his life from being disrupted. More than any other class of drugs, the amphetamines foil users' attempts to reach equilibrium with his habit because they induce such powerful and unrelenting tolerance. Consequently, users develop erratic patterns of use, such as "spree shooting" alternating with barbiturates and eventually with heroin.

Clinical observers56 agree that there are at least two types of amphetamine dependency that develop: ( 1 ) The very bizarre, speed freak, hippie use of enormously high doses, usually intravenously. Gordetzky57 believes that eventually all these people develop paranoid psychoses; (2) the so-called housewife syndrome, in which certain users of amphetamines begin because of either a desire to lose weight, a mild depression, or simply the need for a lift in the mornings to get started in a day characterized by housework and young children. The latter has never been involved in research. Whatever psychological research is going on simply tries to indicate the kinds of pathology that either results from enormous doses of amphetamine or causes people to begin to use the drug. The more general question of drug use in the population at large, which relates more to ordinary avenues of introduction, such as the medical profession, advertising, and so on, is not included in any of the NIMH projects or any other research that is currently being done on amphetamines.

4. NARCOTICS

Although specifically the concept of narcotics refers to opiates, a wide variety of drugs have at one time or another been listed as narcotics. It is well known that marijuana is classified legally under narcotics, and at different times such drugs as coffee have been declared a narcotic. In effect the term "narcotics" has wine to have a nonspecific meaning that implies danger, addiction, and nonmedical uses. "The very word narcotic has taken on sinister meaning in American culture. There is probably no field—save perhaps religion and politics—so replete with popular misinformation and purposeful misrepresentation. It is enough that a substance be called a narcotic to draw away aghast."58

Probably more money is being spent in research on narcotics (in the more specific sense of the opiates) than on all other drugs together. The reason for this is the enormous investment in clinical research" on addicts attempting to • withdraw from heroin, morphine, or the like, who go to treatment centers for methadone maintenance. The largest program is in New York City and is headed by Dr. Vincent Dole and Dr. Marie Nyswander, who began the push for methadone maintenance and have done most of the original clinical research. Many other cities have equivalent centers and are trying a whole variety of methadone programs.

The magnitude of the NIMH commitment to opiate programs can be gathered from the figures: $3,149,000 in fiscal 1969 alone. They funded numerous civil commitment programs as well. No exact figures are available for the amount of money invested in the

Fort Worth Clinical Research Center and the Lexington Clinical Research Center, but certainly more than $12 million was invested in each of these operations. The aim of the opiate programs across the country has basically been a comprehensive approach to management of the addict. The centers vary in their approaches but uniformly attempt to operate within a community to set up liaisons with judicial and rehabilitation agencies and specifically try to support and guide the addict as well as his family. They all hope for the addict to go through periodic examinations and to find his way to complete abstinence or, at the very least, methadone maintenance. While some provide group psychotherapy and educational and vocational programs, they vary from community to community. Of the more specific research projects, as opposed to treatment programs funded, only one would fit into the category of psychological research. This program is designed to show that the pathologies of extreme delinquents, such as addicts, make them poor partners in any task needed to support and sustain group life, and that they turn to drug use as a method of achieving shared relations.

Of 26 other studies funded by NIMH, only one could be considered 'sociological. This one has to do with the movement of young ghetto dwellers into an identity as an addict. The paucity of psychological and sociological research funded directly by the NIMH reflects the massive investment in clinical research centers. Many of the activities of the centers may be more directly sociological and psychological than is evident in the report available to us. From the "Drug Abuse" report it seems that the trend is to specialize in clinical pharmacological studies of a series of narcotic antagonists, drug metabolism in kinetic studies to establish a mathematical model for drug dose-response curves and a method of analyzing these curves, experimental psychiatric studies on the effects of drug use on sleep, the biochemical and pharmacological properties of analgesics, and the neuropharmacological effects of morphine on electroencephalograms. Also a number of animal studies using monkeys try to find the specific brain structures involved in the addiction syndrome. Investigators are studying the development and tolerance of physical dependency in mice, just as another granted project studies a differential rate of opiate-seeking behavior in aggressive and nonaggressive white mice. Self-administration in rats is also being studied.

A great deal of money and effort is being put into the study of narcotics by the NIMH. It is impossible at this point to evaluate the validity and worth of the investigations or the sort of things that are being investigated. It is easy to criticize what is being done but hard to prepare the kind of research that would produce information to help with essential decisions. However, it is fair to say that from the tone of the report, as shown by the opening statements that lead into the section on narcotic addiction—"While narcotic addiction appears to be epidemic in our urban slums among economically deprived young people, it is in fact an epidemic problem afflicting people at every level of our society"6° —it does not take into account the different quality of use mentioned earlier in the discussion of the numbers game of narcotic addicts; that is, the attempt to describe drug use purety on a quantitative basis. For instance, during the period of 1952 to at least 1968 the addict population remained stable at about 55,000 to 65,000 and, in ratio of addicts to population, declined slightly.6' If one goes over the figures, the remarkable thing is not the constancy of the addict and his habits, but rather that the addict deserts his habit quite easily. Kolb and DuMez62 estimate the number of addicts in 1892 at 246,000. By 1915 this figure had declined by 31,000 to 215,000, and by 1922 it declined by another 105,000 to 110,000. Four years later the number fell still more, so that it was reduced to 100,000. In 1935 there was an estimated increase to 122,000, but three years later this had decreased by 96,000 or 79,000, depending on whether one reads the 1938 or 1939 report of the Federal Bureau of Narcotics (FBN). In 1938 they estimated that there were 26,000 addicts in the nation, and in 1939 estimated 43,000. The sensational increase in addiction between 1939 and 1955 or 1957 totaled 17,000 or 1,000 persons, depending on which year one takes as the closing date, because in 1955 the FBN estimated 60,000 addicts in this country, but in 1957 estimated only 44,000.63

Kolb and DuMez cite the estimate of the special narcotics committee of 1919, which was one million addicts in the United States." Using the FBN figure for 1928 of 100,000 addicts, it would mean that 900,000 addicts deserted the use of their drugs within ten years." Obviously research can be done that would aid us in understanding the extent to which the narcotic addict can desert his dependency more readily than has been previously supposed. Research could also, of course, be done on the ways in which statistics and figures are collected. Moreover, greater knowledge about the tenacity of addiction might help the public understand what addiction is and lead to a more informed attitude toward policy.

5. SEDATIVE-HYPNOTICS

Barbituric acid was synthesized in 1863;66 the acid itself is not a central nervous depressant. The first active derivative, barbital, was not reported until 1902,61 and was not introduced into medical practice, as Veronal, until a year later." Within a few years there was a literary reference to chronic barbiturate intoxication and the occurrence of withdrawal convulsion in Germany." Seven years elapsed between the first use of a barbiturate in a clinic and a qualifyilig report of the dependence potential of this class of drugs published by Isbell," in 1950, who demonstrated through a series of controlled experiments in man that the abuse of barbiturates induces physical dependency. In 1970, Carl Essig," the Chief of the Neurology Section of the National Institute of Mental Health Clinical Research Center, Lexington, Kentucky, reported, "The basic neurophysiological and neurochemical mechanisms underlying the barbiturates withdrawal syndrome are unknown."

The sedative-depressive drugs are discussed last in our report because they include alcohol and a whole list of other drugs in general usage. The alcohol-barbiturate class, like the opiates, produces both psychic and physical dependency. In the alcohol-barbiturate group are the paraldehydes and chloral hydrates, as well as newer sedatives that seem to have clinical effects like the barbiturates.

Controlled experiments on the treatment of withdrawal from the newer sedative drugs have not been performed in man. The probability of cross-dependence between barbiturates and these drugs makes it likely that the principles of barbiturate withdrawal treatment can be applied to nonbarbiturate sedative agents. It is also thought that pentobarbital can be used for this purpose, but diphenylhydantoin (Dilantin) or phenothiazines are not recommended.72

The prevention of sedative-hypnotic drug misuse has been defined by an AMA Committee on Alcoholism and Addiction as a role a physician might take "in establishing a potentially dangerous type of therapy even though it does not always lead to significant tolerance or physical dependence."73 This AMA committee also listed the ways in which physicians might contribute to the misuse of sedatives. Thus, a statement was made against the prolonged and unsupervised administration of barbiturates for symptomatic relief often without adequate diagnosis or knowledge of the patient's past experience with medications or attitudes toward drugs. This same statement is also applicable to the other sedatives listed in this presentation. Other committee recommendations were as follows: that physicians resist any patient's demands for increased quantities of drugs; that he not shift the patient to another or newer sedative in the erroneous belief that such agents have no abuse potential; and that he not write refillable prescriptions for barbiturates or their substitutes without thought of cumulative effects, additive action with other depressants, or the possible establishment of strong psychological or physical dependence." In addition to these AMA committee recommendations it is well for physicians to avoid prescribing sedatives to narcotic addicts, sociopaths, some alcoholics, and those known to refill prescriptions sooner or more frequently than specified. Perhaps clinicians can play a more important role in preventing the misuse of sedative-hypnotic drugs in a larger and less devious group of patients variously referred to as "anxious," "psychoneurotic," etc. The prevention of moderate degrees of sedative-drug intoxication is an important public health consideration, not only because of the social implications of such impaired behavior but because moderate or periodic states of intoxication might lead to continuous abuse and physical dependence. Thus, the effect of depressant-drug intoxication on automobile driving, work performance, and social interaction should be considered by the doctor when he prescribes such drugs.

Not alone is the abstinence syndrome far more serious with this class of drugs than with those associated with opiate withdrawal. Convulsions, temporary psychosis, and death are not infrequent complications. Even drugs considered mild tranquilizers such as meprobamate (Miltown, Equanil) have been known to cause coma and death following both excess dosage and abrupt withdrawal. Barbiturates are often implicated in accidental self-poisoning because tolerance of lethal dose does not develop as fast as tolerance of the hypnotic doses.75 Essig" reports a similar situation with a so-called minor tranquilizer. The minor manifestations of their withdrawal are also like those of barbiturate abstinence.

Despite the rigorous presentation of official medical concern about barbiturates and the impressive reports as to potential difficulty, there are only two projects specifically listed by the NIMH" that are principally concerned with barbiturates. A colony of barbiturate dogs has been established to study drug preference and social effects of drug dependence. The question raised by this research is whether more dominant and fearless animals self-administer as much of the drug as those that are more fearful. Then, upon withdrawal, it will be determined whether abstinence was severe in those monkeys or dogs who had shown the most marked drug effect and whether they were necessarily those who self-administered the higher daily dose.

The other project concerns a study of rats' hypersusceptibility to a subsequent dose of barbiturates once a tolerance level has been established. This research is intended to obtain some indication of the mechanism for delayed alteration and responses. It is hard not to speculate that the paucity of research in the sedative-hypnotic group is a strong indication of both the moral bias of research in drug use and the lack of understanding of the concept of the influence of set and setting on such drugs. After all, alcohol is a sedative-hypnotic and is the most used drug in this country. We have no wish to get involved in the fervent moral question brought up by so many marijuana smokers as to whether it is more or less moral that one uses alcohol rather than marijuana. In fact, the sedative-hypnotics as a group are the most used drugs; a user develops tolerance, withdrawal, and a whole variety of abstinence syndromes, as well as physiological damage related to their use. Nevertheless, there is relatively little research about the barbiturates and there is relatively little concern that we know so little about their action.

CONCLUSION0

The sedative-hypnotics best illustrate the two issues: morality and influence of set and setting, and how little they are considered in the entire complex of drug research. It is not that the research per se is poorly organized or executed. Every project is a building block to increase our knowledge. It is certainly true that the accumulation of knowledge in these areas may lead to change in legal controls and social attitudes toward one drug or another.

But there is a problem in drug research when it is pursued essentially from the point of view of pharmacological action. Although there are research projects that investigate the extent and patterns of use, and the psychology of users, most projects revert again and again to the drug itself. In one way or another, scientists are trying to derive a method of predicting individual response to a psychoactive drug from consideration of the drug. They accept intellectually the proposition that drug, set and setting are inter-dependent in shaping the drug response; but they proceed, if one can deduce from the research done, as if the one factor, drug, is more determining than the others.

There should be greater interest in the "high" state itself and in the forceful fact that every culture that anybody ever studied (except possibly the Eskimo) has found some way to get high and has felt it important to have this experience. What's more, the experience has had important social ramifications and is deeply connected in many cultures with social rituals of importance. It has made little difference whether the drug of choice was alcohol, some form of hemp, or one of the opiates or cocaine; the particular culture that has adopted the drug has shown an intense desire to acquire both personal and social relationships through the drug experience.

Trouble begins when certain individuals in a social setting which rigidly defines social irregularities predominate over ritualized and regularized drug use. Lacking a consensus of approval, a society makes drug-taking an antisocial activity rather than one that conforms to the interest of society. Liquor, the pipe, joints, pills, no longer work as well, as drugs become a personal neurosis or a focus of social conflict. It is at this point that more frequent and compulsive use may occur with less and less reward. It can be argued, of course, that for certain disturbed persons this compulsive response will always be predominant. Little research proceeds from this anthropological point of view to help us understand the potential social factors that would create strongly negative set and setting. Thus, we only speculate on the likelihood that under negative conditions of set and setting users will be drawn into drug abuse rather than encouraged to explore the positive social potentials of use.

Considerations of the high itself (the influence of consciousness, the relationship of positive or negative social setting) have been little explored. The focus for research has been on the narrower considerations (of the pharmacology, biology, or sociology of the drug itself), leaving the field wide open to those who come at it, equally narrowly, from the opposite point of view.

It is hardly surprising that many people would like to investigate the concept of altered states of consciousness.78 The emphasis on subjective experience leads toward a variety of directions—some interesting, such as current efforts to train patients with heart block to try to learn to control the sympathetic nervous system. It can also lead to preoccupations with magic, astrology, and tarot cards. It is not an uncommon human characteristic for one narrow preoccupation to leave the way open for its opposite. When research denies so much of human consciousness, it is not surprising that those emphasizing the side denied will move into the void and gain credence and respectability otherwise withheld from them.

Research simply cannot be convincing if it is conceived on the basis that drugs may not produce pleasure without a compensating harm. This ethic is as valid in its own way as the belief in spirituality, but no more so. When an effort is made to superimpose either view and when research becomes one of the devices to do so, we have moved far from the scientific tradition. The purpose of this critique of research has been to broaden the perspective from which drugs are considered. It has been repeatedly demonstrated that attitudes play an essential, important role in shaping opinions, not only in terms of the final social control, but also in limiting the horizons of scientific investigation. Drug users have told us again and again that they are experiencing things different from what they had been taught. Those who have studied the issue have found that myth and misconception play an enormous role in our entire view of drug use. We have tried to show the change in the educational experiences available to the generation now growing up through television and other technical, social, and psychological events, just as we have tried to be clear about the fact that the essential nature of man is unchanged.