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Human Psychedelic Research:
A Historical And Sociological Analysis

Undergraduate Thesis
for the Degree of Bachelor of Arts
in Natural Sciences (History and Philosophy of Science)
by Luke Williams, April 1999
Cambridge University
Supervisor: Martin Kusch







Contents

Acknowledgements

Introduction
            What is a Psychedelic?
            Why study Psychedelics?

Part One: The History of Psychedelics Research
            The Discovery of LSD
            Early Research and Use of LSD
            The Banning of Psychedelic Drugs
            Underground Research: Dr. Alexander Shulgin
            The Renewal of Legal Human Experimentation
            The Future of Psychedelic Research

Part Two: The Sociology of Psychedelic Research
            Evidential Cultures in Psychedelics Research
            The Politics and De-Politicising of Psychedelic Research
            Methodology of Psychedelics Research
            Trust and Testimony
            Blinds, Experience and Ethics

Conclusions

Bibliography

 

 

 

 

 

 

 

Acknowledgements

            I would like to express my thanks and gratitude to the following people:

            Roland Neal, for the loan of books, assitance in information gathering and inspiration for this project.

            John Rogers, for supplying me with psychological knowledge at short notice.

            John Block, for letting me keep his copy of “PIHKAL” for so long.

            Bear Wilner and Rick Strassman for mailing me documents from across the Atlantic.

            Martin Kusch, for agreeing to supervise an unothodox topic and giving me timely advice and criticsm.

            Finally, everyone on the MAPS forum who has supplied me with references, information and advice.

 

Introduction

            The field of human based research into psychedelic drugs has in the last ten years become a legitimate field of study, after years of repression by governments around the world. This study explores the history and current work done by scientists into the study of the chemical nature, means of action and possible therapeutic uses of psychedelic drugs in humans. It falls into two sections: Firstly, a description of the history of psychedelic research from the beginning of the century until the present day, which explains how a scientific culture based around psychotherapy emerged, shows how the new field was restricted and neglected due to social and political considerations from the 1970s until the 1990s, and details the reasons and factors involved in the renewing of human psychedelic studies. The second section takes a sociological approach, using elements from the sociology of scientific knowledge in particular, to explain the reasons why psychedelic research is conducted the way it is. It concludes that the scientists involved in modern research are determined to make their work more acceptable to their audience than that conducted in the 1960s, which has a strongly negative image associated with it. This includes discussion of how some of the unusual methodological and ethical issues raised in psychedelic studies are tackled.

 

What is a Psychedelic?

            The word “psychedelic” was coined by the psychiatrist Humphry Osmond in 1956, during a correspondence with the novelist Aldous Huxley.[1] He chose this new term because it was uncontaminated with previous associations, unlike the existing terms used to describe these drugs: “hallucinogenic” or “psychotomimetic”, and because these terms emphasise certain aspects of the experience. Psychedelic is derived from the Greek, meaning literally “mind-manifesting”, and the most useful definition of the term comes from Grinspoon and Bakalar: “a psychedelic drug is one which, without causing physical addiction, craving, major physiological disturbances, delirium, disorientation, or amnesia, more or less reliably produces thought, mood, and perceptual changes otherwise rarely experienced except in dreams, contemplative and religious exaltation, flashes of vivid involuntary memory and acute psychoses”.[2] This definition thus excludes drugs like opium, amphetamines, cocaine etc., all of which can produce psychedelic like states, but not as their primary effects. My study will also not discuss THC, the main active ingredient in cannabis plants, for two main reasons: (1) It is generally not considered to be in the same class as the other “true” psychedelics[3], although it does produce some psychedelic effects at high levels, as it has different qualitative effects. (2) The literature on the chemistry, pharmacology, historical use and medical applications is so huge as to be almost as big as the rest of the other psychedelics together.

 

Why Study Psychedelics?

            Why are scientists interested in studying psychedelic drugs? And why is this area of science of interest to the historian or sociologist of science?

            To answer the first question, the scientists themselves must respond: here are the reasons given for conducting psychedelic research by Dr. Rick Strassman, one of the leading researchers of the early 1990s. “Firstly, they [hallucinogenic drugs] elicit a multifaceted clinical syndrome, affecting many of the functions that characterise the human mind, including affect, cognition, interoception, and perception. Characterising hallucinogens’ properties will enhance understanding of important mind-brain relationships...Second, naturally occurring psychotic syndromes share features with those elicited by these drugs. Understanding effects and mechanisms of action of hallucinogens may provide novel insights and treatments in endogenous psychoses. Third, increasing use and abuse of hallucinogens over last several years, particularly LSD, by young adults may produce a similar spate of adverse psychiatric sequelae seen with the first wave of their illicit use in the 1960s. Treatment of these adverse effects consume scarce public resources and safe, selective and efficacious treatments of acute and chronic negative effects of these drugs are needed. Finally, the enhancement of the psychotherapeutic process, sometimes in treatment refractory patients, reported by earlier studies has relevance to current emphasis on time-limited psychotherapeutic interventions.”.[4]

            Why should a historian study the psychedelic sciences? The obvious answer is that all branches of science deserve study, as all exhibit different methods and techniques. Psychedelic research is particularly interesting for several reasons: the study and therapeutic use of psychedelics is one of the most controversial and heavily politicised fields of science, which many non-scientists, from politicians to parents to activists and users have opinions on. Psychedelics also provide an interesting interface between the two cultures of science and art- the use of such drugs has had a hand in shaping popular literature and music from the 1960s onwards, and yet they are well characterised chemicals with a place in the scientific literature too.

 

 

 

PART ONE: A History of Psychedelic Research

            Psychedelic substances have been present in nature and used by many cultures for hundreds, if not thousands of years (carvings found in South America suggest that hallucinogenic mushrooms have been used there since before 1000 B.C.).[5] The plants which contain these substances vary widely, and include cacti, mushrooms, morning glory vines and even common reed grasses. The earliest scientific research done on these fascinating chemicals was the isolation of the main psychoactive alkaloid found in the peyote cactus by Heffter in 1896, which he named mescal.[6] There were other, small-scale studies done into mescaline and other psychoactive plants at the turn of the century, but scientific interest in such substances was not truly aroused until the discovery of the first synthetic hallucinogen - Lysergic Acid Diethylmide (LSD - from the German Lysergsäure-diäthylamid).

 

The Discovery of LSD

            LSD was first synthesised in the 1938 at the Sandoz research labs in Basel, Switzerland by Dr. Albert Hofmann.[7] Hofmann and his colleagues were conducting research into ergot, a fungus which grows on rye and other grain producing plants, and had caused mass poisoning in the middle ages which were commonly known as “Saint Anthony’s fire”. The symptoms included hallucinations and gangrene in the extremities due to a contraction of the blood vessels, and ergot had been used research was being done to see if this contracting attribute could be useful in modern medicine, in reducing blood loss during childbirth. The alkaloids present in ergot had been isolated in the early thirties, and Hofmann was working on the partial synthesis of ergobasin, one of these alkaloids. The basic group of all the ergot alkaloids is a compound known as lysergic acid, and Hofmann succeeded in synthesising ergobasin (lysergic acid propanolamide) in the lab, which allowed him to produce modified variants of the natural compound. He produced several derivatives of the lysergic acid and tests were done on their effectiveness in contracting blood vessels in the womb. Some of these derivatives proved to be more effective than the natural alkaloid, and were subsequently mass-produced and introduced into general medical practice. Lysergic acid diethlyamide (abbreviated to LSD-25 as it was the 25th modification of the natural alkaloid) was only 70% as effective as ergobasin in controlling blood flow in the uterus, and had no other observable effects, so testing was stopped  and the compound was shelved and forgotten. It was not until five years later when Dr. Hofmann decided to conduct further tests on LSD-25 and, by chance, accidentally ingested a microscopic amount of lysergic acid by absorbing it through his skin that its psychedelic properties became known. Dr. Hofmann subsequently carried out a self-experiment to confirm that it was in fact LSD that was the psychoactive compound, and took 250µg (he had no way of knowing this was a large dose - no other chemical had ever been synthesised which produced physical effects at lower doses). This led to his infamous bike ride home heavily under the influences of a full-blown LSD experience. He was able to make it home guided by his assistant, although during the journey he was unsure at times whether he was moving or not. At home, he called a doctor, worrying that he was going mad, or even dying - once friendly faces seemed like grotesque masks, and he was filled with a sense of fear and dread. The doctor examined him, but could find nothing abnormal except for extremely dilated pupils. The horrific nature of the experience slowly waned, to be replaced by pleasant visual hallucinations - intense, alternating colours. The next day, Hoffman awoke feeling refreshed.

            The new compound was tested by several other researchers at Sandoz.[8] After verifying its effects, LSD-25 was tested for toxicity in animals, and Sandoz decided to continue research in the hope of producing a marketable product. The son of Arthur Stoll (who was the head of the pharmaceutical department at Sandoz), Werner Stoll, was the first person to use LSD in a psychiatric environment, were he discovered that low doses allowed repressed material to surface easier.[9] After Stoll published his findings, Sandoz marketed LSD under the trade name “Delysid” as a tool to aid the release of repressed material and as method of allowing the psychiatrist to experience the world of psychotic patients.[10]

            The subsequent explosion of interest in LSD and psychedelics in general in the postwar period can be explained by several factors: Firstly, the discovery and manufacture of LSD only became possible after the emergence in the 20th century of large scale industrial chemistry, with all its techniques and equipment. Before this period, individual chemists did not have the resources to investigate and, importantly, produce chemicals of high purity. Second, the relatively new fields of psychiatry and psychoanalysis gave a range of possible applications for the new drug. Doctors studying psychosis were looking for a possible chemical cause of madness, and psychotherapists were keen to investigate any drug which might make the therapy process easier. The blossoming of research into the effects and applications of LSD (and quickly, other psychedelics) will be discussed in the next section.

 

Early research and use of LSD

            The first experimental use of LSD was as a psychotomimetic - a drug mimicking psychosis.[11] The idea that a chemical substance could induce psychosis or schizophrenia was first put forward by Emil Kraeplin in 1892[12], who suggested that such disorders could be produced by the overproduction of a endogenous chemical in the brain. The desire to find a chemical which was a biochemical cause of madness was thus already present when LSD was discovered. Yensen describes LSD as an exemplar, in the Kuhnian sense, for the psychotomimetic view: “[LSD] served the same organising and limiting functions for research in this area as have other major paradigms of science described by Thomas Kuhn”[13] - it lead to the resurrection of older theories of the biochemical origins of schizophrenia and psychosis, and influenced the design and implementation of experiments through the early period of the 1950s. This view was very appealing to scientists of the time, as the introduction of tranquillisers at around this time suggested that since there were now anti-psychotic and psychotomimetic drugs, the biochemical basis for schizophrenia would soon be discovered.[14] The psychotomimetic paradigm was thus the basis for the first experiments with LSD, and early experiments were characterised by a negative slant on the psychedelic experience. Researchers noted “distortions” and “upsets” in reality, and used primarily negative adjectives to describe the effects, as they viewed the LSD state as being similar to psychosis.[15] The accepted paradigm, that LSD produced psychosis, dictated that the experience should be described in these terms.

            Much of the early, psychotomimetic research was covertly sponsored by a CIA project known as MK-ULTRA.[16] Since the war, the CIA had been conducting investigations into developing a “truth drug” that could be used in interrogations to allow the interrogator to impose his will upon the subject, and thus force the subject to reveal whatever secrets he might be guarding. In 1953, Project MK-ULTRA was formally approved, to investigate the potential of a wide range of drugs as possible truth serum. The CIA quickly concentrated on LSD as the prime candidate, and after securing a supply from Sandoz, the Chemical division, led by Sid Gottlieb, began conducting research. It soon became clear that they did not have the time or manpower to do full behavioural and psychological experiments, so they began sponsoring research. Two organisations were used as fronts, the Josiah Macy Foundation and the Geschickter Fund for Medical Research, and many researchers received large grants from them to conduct some very ethically dubious studies, including dosing patients with LSD without their prior knowledge or consent.[17] After the exposure of a number of scandals - the most serious being the suicide of an army chemist who had been dosed with LSD unknowingly[18] - interest in the project slowed. It was also becoming clear that LSD was not a particularly effective truth drug - the effects were too unpredictable for that.

            From this initial psychotomimetic model, two new paradigms emerged. They were both based on therapy, rather than objective descriptions of the drug’s effects. Two different kinds of therapy were eventually to emerge: psychedelic therapy and psycholytic therapy. These two types of therapy were characterised by Dr. Hanscarl Leuner as follows[19]:

 

 

PSYCHOLYTIC THERAPY

PSYCHEDELIC THERAPY

Low doses of LSD (30-200µg) or psilocybin (3-15mg) producing symbolic dream images, regressions and transference phenomena.

High doses of LSD (400-1500µg) leading to so-called cosmic-mystic experiences. Oneness and ecstatic joy are attained.

Activation and deepening of the psychoanalytic process.

Without foundation in the classical psychological theories. Parallels to religio-psychological experience, mystics, satori.

Numerous sessions required.

One single “overwhelming” experience is aimed at.

Analytic discussion of experienced material in individual and group sessions.

Extremely suggestive preparation and use of specific surroundings and music. No detailed discussion of experience.

Reality comparison, and attempt to adapt experience to everyday life.

Adaptation to reality not desired, but rather the fixation of the psychedelic experience.

Goal: cure through reconstruction of personality in the sense of a maturing process and loosening of infantile parental bonds, requiring several months

Symptomatic cure in a change of behaviour not further defined

Classical indications for psychotherapy: neuroses, psychosomatic cases and further: psychopaths, sexual perverts, borderline cases. Neither alcoholism nor psychoses.

Alcoholism, neuroses?

 

            Psycholytic therapy was first developed in England at Powick Mental Hospital by Dr. Ronald Sandison in 1953, after he read an article by Busch and Johnson which “was the stimulus which encouraged me...to think of starting to use LSD therapeutically in England”[20]. Psycholytic therapy became predominantly a European phenomena, refined and used by Leuner at the University of Goettingen after he read Sandison’s first paper on LSD in 1956,[21] whereas psychedelic therapy was developed and used almost exclusively in America and Canada.

            Busch and Johnson had observed that patients were sometimes better able to elaborate repressed material when they were under the influence of toxic delirium brought about by sodium pentothal, insulin shock or electroshock therapy.[22] Thus, with LSD widely regarded as a psychotomimetic, it was not long before Busch and Johnson tried it on their patients. LSD offered immediate advantages over these other agents: patients under the influence of LSD did not suffer from amnesia, or delirium which made communication difficult, both of which were characteristic of the previously explored methods.[23] From their studies, Sandison developed a system of therapy which was to become known as psycholytic. He and his colleagues gave relatively small doses of LSD to their patients as part of the psychotherapeutic process.[24] The theory behind psycholytic therapy is based on Freudian psychoanalysis. The idea is that LSD acts as primitivizing agent by inhibiting synapses in the brain involved with maintenance of ego-identity. This leads to a breakdown of ego defences and boundaries, resulting in depersonalisation, derealisation and mystical experiences which may enable the patient to see some of his conflicts.[25]

            Psychedelic therapy was first developed by Abram Hoffer and Humphrey Osmond in Canada in 1953[26], and also grew out of the psychotomimetic paradigm. Osmond noted that many alcoholics who had recovered had gone through a period of “hitting bottom” where they experienced delirium tremens and its accompanying hallucinations. He hit on the idea of trying to induce a DT-like experience through LSD, one that was so horrible that it would frighten their patients away from drinking. They administered high doses of LSD to their patients; Abram Hoffer explains what happened “We began to treat alcoholics with LSD, trying to make them have this absolutely horrible experience. To our amazement we found that we couldn’t. In spite of everything we tried, they’d have a good experience...they enjoyed it, they felt good, they saw strange things, they were excited about it”.[27] So they changed their approach, and attempted to make their subjects have a good, transcendental experience. They introduced pleasant, non-threatening surrounds and talked them through the experience, and try to help them relate it to their drinking. The emphasis was on inducing a “mystical” type of experience, so the patient would go through an almost religious conversion and give up their drinking.[28] This produced better results, but was clearly not in line with the predominant psychotomimetic paradigm. So Osmond coined the term psychedelic, to differentiate their model from the older idea of LSD as being similar to the psychotic state. As mentioned above, psychedelic therapy was predominantly an American phenomena, but another major use of this type of therapy was in Prague. Here, Stanislov Grof used LSD to treat heroin addicts in much the same way Osmond and Hoffer used it to treat alcoholics.[29]

            Both of these two new kinds of therapy showed that the effects of LSD were not exactly like those caused by psychosis or schizophrenia, and the psychotomimetic paradigm began to lose support. The varying qualities of the psychedelic experience also brought the now familiar concept of the importance of “set and setting” to the use of LSD as an adjunct to therapy. The patients mind “set” and the “setting” of the environment could have profound influences on the nature of the trip, as was observed when less thoughtful researchers tried to replicate Osmond and Hoffer’s results, but instead of keeping their subjects in a friendly environment, they kept them restrained in a hospital. Unsurprisingly, the results were not good.[30]

            During this period, two new psychedelic chemicals were discovered: psilocin and psilocybin. These were isolated by Dr. Hofmann at Sandoz, but they had come to him from the explorations of the ethnobotanist Gordon Wasson.[31] He had been attempting to locate the semi-mythical hallucinogenic plants used in the religions of the native tribes of the South American rainforests. After a year of searching he finally located the teonanacatl or “flesh of the gods”, as they were known: mushrooms of the genus Psilocybe. Eventually, a number of the mushrooms were sent to Sandoz, where Hofmann isolated the psychoactive alkaloids. These new psychedelics produced an effect similar to LSD, but one which is often characterised as being gentler, or less intense.[32] They were quickly integrated into the existing therapies.

 

The Banning of Psychedelic Drugs

            A general malaise that developed in many different groups of therapists and researchers during the ‘50s was a complacency in the control of their supplies of LSD. The popularisation of LSD by authors Aldous Huxley and Gerald Heard, and later Tim Leary, the Harvard psychologist who was to become one of the founding fathers of the ‘60s counter-culture movement, led to unqualified people setting up LSD therapy practices, which was often extremely financially lucrative. Psychiatrists also began giving LSD to their friends and family, and holding LSD “parties”.[33] In 1962, as the recreational use of LSD spread, Dr. Sidney Cohen published an article warning of the dangerous side effects that could result from improper use of LSD.[34] Cohen had been involved in LSD research since 1957, when he received a consignment of LSD and began research into its psychological effects in Los Angeles. He had previously published an article in 1960 that concluded that LSD was safe if used on carefully screened patients in a correct environment[35], but the spread of illegitimate use and an increasing number of patients who had had LSD treatment and developed side effects encouraged him to present a more negative attitude. The coincidence of his report with the breaking thalidomide crisis forced the government to reassess the laws involving “Investigational Drugs”. These regulations were tightened by Congress, with the introduction of the Kefauver-Harris Drug Amendments in October 1962, which required the FDA (Food and Drug Administration) to give approval for the testing of investigational drugs. Sandoz stopped supplying LSD to any physician who asked, and only gave LSD to doctors from the NIMH (National Institute of Mental Health) or state commissioners of mental health.[36] As the popularity of LSD spread to the sixties “counter culture”, the government introduced further regulations. In 1965 the Drug Control Amendments forbade the manufacture and sale of psychedelic drugs, and the year after Sandoz stopped supplying LSD altogether and almost all LSD research was stopped. In 1968, the NIMH Division of Narcotics Addiction and Drug Abuse was created with Cohen as its first director.[37] In 1970, the Controlled Substances Act came into force, creating the five drug Schedules in place today:[38] substances in Schedules I and II require a special license from the FDA too posses or use in experiment. Schedule I is the most restrictive category, with drugs in it defined as having no medical use and as being unsafe to use, even under medical supervision, with a high potential for abuse. The other schedules are less stringent; Schedule II drugs are still dangerous drugs with the potential for abuse but with some medical applications. Schedule III drugs have moderate potential for abuse and are considered safe under medical supervision. The government bodies that control aspects of drug scheduling and research are the DEA (Drug Enforcement Agency) and the FDA. The DEA controls which drugs are scheduled, and who has the right to possess and manufacture such drugs, and gives licenses to researchers. Researchers of all kinds of drugs, not just scheduled ones, must submit their experimental design and protocol to the FDA for approval.

            Subsequently, the United States applied international pressure to encourage other countries to implement similar controls over psychedelic drugs.

            Traditional historical views have been that the governmental restriction and regulation was due to social considerations; attempts to control the growing counter-culture movement. The historian Steven J. Novak has argued that medical and subsequently governmental opposition to LSD was due to health concerns, rather than social ones and the medical profession, rather than being pressured by the government to oppose LSD lobbied the government to tighten controls.[39] However, looking at the studies published at the time, it seems that Cohen’s critique was motivated by the spreading social use. His critical paper includes only nine cases of serious complications, and at that time thousands of people in the states were using LSD on a regular basis.[40] Despite enormous amounts of sensationalism in the press, LSD related murders and suicides were rare. At the Congressional hearings conducted in 1966, it became clear that the worry wasn’t the few cases where a bad reaction lead to long lasting damage, but rather the non-conformist attitude that seemed prevalent among the majority of LSD users.[41] Sidney Cohen himself, when testifying at the hearings said “We have seen something which in a way is most alarming, more alarming than death in a way. And that is the loss of all cultural values...these people...are deculturated, lost to society, lost to themselves”.[42] Up until the spread of the non-medical use of LSD, Cohen was happy to declare it safe in the hands of experienced doctors who could correctly screen out potential bad cases.[43] It was only with people like Leary promoting psychedelics as being safe for everyone to use, and putting forward ideas of nonconformism and the counter-culture lifestyle, that Cohen felt it necessary to produce a critical study.[44] Up until that point, criticism that LSD was unsafe to use had little data to support it - Cohen’s earlier report was unchallenged in the field.[45] Even in his second report, which contained the nine adverse case studies he recommended that use should only be “restricted to investigators in institutions and hospitals where the patients’ protection is greater and appropriate countermeasures are available in case of adverse reaction”.[46] However the end result was the complete halting of research, responsible or irresponsible, when the FDA gained control over investigational drugs.

            Although the crackdown and subsequent moratorium on human psychedelics studies was due to social considerations, many of the studies at the time were far from perfect. Although high rates of success were claimed by therapists in both of the different schools of LSD therapy, few long term studies were done to check that the results were permanent.[47] Also, effect of “set and setting” mentioned above, although known, was hardly ever mentioned in clinical reports. Since these factors are extremely influential on the outcome of the experiment, there is little wonder that results were difficult to replicate: everyone was conducting their studies under widely different conditions.

 

Underground Research: Alexander Shulgin

            After the banning of LSD, psilocybin and mescaline, the whole program of scientific study into the properties of psychedelics in the U.S. changed. During the 70’s and 80’s, there were no human studies conducted.[48] A large number of animal studies were conducted, most into the toxicity of the psychedelics. At the same time, the underground search for new psychedelic drugs began in earnest. Many of those searching to find new drugs were simply looking to make a profit by supplying new “highs” to those who wanted them on the street. Others were looking for ways to produce new chemicals with similar properties to the banned hallucinogens, but which were legal to manufacture and sell. A few researchers, however, were interested in developing new hallucinogens for less material goals. They believed that drugs of this kind had many possible therapeutic applications, and wished to extend the sphere of human knowledge in this area. The most important and famous of these researchers was Dr. Alexander Shulgin. The remainder of this chapter will concentrate on him as the leading example of a scientist conducting psychedelic research outside the general scientific community. First, however, brief mention must be made of the situation in Europe.

            In contrast to the situation in America, several European countries continued with psychotherapy using psychedelics. Hanscarl Luener continued to use LSD, ketamine and MDMA analogues in psycholytic therapy in Goettingen until his death in 1996.[49] However, the European community of psychedelic therapists was disintegrating even before it was fully formed, particularly in Britain. Sandison blamed the escape of LSD from the lab into the subculture, and the movement of those who had been working with LSD into other areas.[50] They “were also hampered by the insistence of some European colleagues that only medical therapists could become members [of the newly formed Psycholytic Society], thus excluding some who had contributed significantly to LSD therapy”.[51] Most of the research and therapy that continued in Europe was done in private practice, and went unreported in the general scientific and medical journals.[52]

            Alexander Shulgin began his career in the 1950s as chemist working for Dow Chemicals, after completing a Ph.D. in biochemistry, and after he developed an insecticide for them which was highly marketable, he was given a free rein to research in what ever he liked.[53] So the turned to psychoactive drugs, an area he claims to have been interested in for a long time. His research consisted of looking at existing hallucinogens, and making derivatives or entirely new compounds with similar structures by moving chemical groups within the molecules. There was no established model for the evaluation of psychedelics, and Shulgin realised the limitations of animals as test subjects - they were useless for determining the qualitative differences between different psychedelics. So he used himself as the experimental subject for the new compounds he developed. However, he also realised that this was not an accepted scientific method of research, and he also set up a series of experiments using Siamese fighting fish (which were popular animals for drug testing at the time), and adding LSD to the water to see if any behavioural changes could be noted. These fish experiments were the scientifically acceptable “cover” that allowed Shulgin to continue his work. He never obtained any results from the fish which might suggest the action of a psychedelic.[54]

            The starting point for his research was mescaline, a drug he himself had sampled in the spring of 1960, and Shulgin began producing synthetic variations of mescaline. The only one that he new of that had already been synthesised was TMA (trimethoxy-amphetamine),[55] which he synthesised, assayed on himself to confirm its psychoactive properties, and then began trying to modify its structure to produce new psychedelics.

            His research continued, and over the next six years Shulgin synthesised and tested a range of different psychedelics. However, his employers began to realise that the end products of his research were unmarketable - in fact, Dow owned patents on several popular street drugs by this point, his work having filtered into the counter-culture of drug dealers and users.[56] So in 1966 Shulgin left the company and spent the next two years back at university studying medicine to broaden his knowledge of neurochemistry and biology and then set himself up as a scientific consultant. He built himself a lab in his garden and furnished it with equipment.[57] He continued to publish in his own name the results of his syntheses in various chemical and medical journals, and supported his research by consultancy work. He was soon acknowledged as an expert on a wide range of psychedelic drugs and in this role appeared as an expert witness in a number of trials. He also refined his method of human assaying for use in group structure and began testing his new substances with a small group of friends[58] (see the section on methodology for a description of Shulgin’s experimental methods).

            A community of sorts grew up around Shulgin and researchers like him - the new drugs spread to psychotherapists and academics, forming a new, mini-psychedelic movement in the 80’s, which Stevens calls the “neuro-conciousness frontier”.[59] MDMA, the most popular of the new, so-called “designer drugs” was enthusiastically taken up by a number of psychotherapists. The most complete clinical study was conducted by Greer and Tolbert[60] which concluded that MDMA was physically safe and was useful in insight-orientated psychotherapy, particularly to aid communication between people in emotional relationships.

            His work continued without many problems from the authorities - he held a Schedule One license allowing him to own and manufacture Schedule One drugs which was necessary for his research and consultancy work, and since he kept mostly to himself, was careful to avoid publicity and never distributed or sold any controlled substances to anyone outside his trusted research group he was tolerated by the U.S. government.

            The first move to curb the work of Shulgin, and others like him, was the scheduling of MDMA in 1985 and the introduction of the Anti-Drug Abuse Act the year after, which contained the Controlled Substance Analogue Enforcement Act.[61] This law made it illegal to manufacture or posses a drug analogue designed for human consumption. An analogue is defined as a drug which meets any one of the following criteria: if its chemical structure is “substantially similar” to a Schedule I or II drug, if it has a stimulant, depressant or hallucinogenic action that is “substantially similar” to a Schedule I or II drug, or if it is intentionally represented as having a stimulant, depressant or hallucinogenic action that is “substantially similar” to a Schedule I or II drug. This law effectively put an end to Shulgin’s legal research: up to that point he had been giving drugs to his research group that were not Scheduled - the Analogue Drug Act meant that these analogues were treated as Schedule I drugs.

            Although the analogue law restricted the proliferation of these “designer drugs”, Shulgin was not himself directly targeted by the authorities until the publication in 1991 of the book “PIHKAL” written by Shulgin and his wife Ann. PIHKAL (an acronym for Phenethylamines I Have Known And Loved) contains two distinct parts - Book 1 is a story based on Shulgin’s life and his study of psychedelics. The book claims that the story is semi-fictionalised, a strategy adopted by the Shulgins to avoid incrimination - if ever asked they could claim that the parts of the book involving the distribution of controlled substances to the research group were entirely fictional.

            Book 2 is even more controversial: it contains a list of 179 different phenethylamines, with notes describing the chemical structure, methods of synthesis, dosage and duration and qualitative reports from members of the research group. The compounds listed include a range of infamous street drugs and drugs of abuse including 2-CB, TMA, DOB and MDMA. Up till this point, the Shulgins had maintained excellent relations with the DEA - they were close friends with Paul Freye, who was administrator of the DEA’s western labs. Over the twenty year period of his DEA license ownership, Alexander Shulgin was inspected several times by DEA agents, who found nothing out of order with his work.[62] However, after the publication of PIHKAL, hostile feeling towards Shulgin’s research became much more pronounced. Two years after the book was published, DEA agents called again, and this time found a number of violations of DEA regulations.[63] The DEA attempted to get Shulgin’s lab shut down on environmental health grounds, but the inspectors from both the State Environmental Protection Agency and the Federal Environmental Protection Agency failed to find any violations serious enough to get the lab shut down.[64] The suggestions they made were carried out by Shulgin, but the DEA demanded that Shulgin hand over his license and pay a $25,000 fine for violations of DEA Schedule 1 license rules. The Shulgins were extremely surprised at the DEA’s reaction; they had had a model relationship with the authorities for over twenty years and had never had any problems with the DEA inspectors before. In their eyes, it was clear that the motivation for this clampdown was political - before the publication of PIHKAL the DEA had been willing to tolerate Shulgin’s research, but after putting his results into the public domain, they felt they could not allow him to continue.[65]

            The eventual result of this was the Shulgin’s second book, published in part as a retaliation to the DEA’s closing of the lab. The new book, TIHKAL (Tryptamines I Have Known And Loved) was again subdivided into two main sections: Book 1 contains a collection of essays by Shulgin and his wife on various aspects of psychedelics, Book 2 contains a list of 55 tryptamines and descriptions of structure, synthesis, dosage, duration and qualitative effects. There are also several appendices on natural alkaloids: one on cactus alkaloids, one on carbolines and one on histamines. Each appendix contains an index of all the members of the chemical family and where they are found in nature.

            In contrast to PIHKAL, Book 1 contains the most politically sensitive information. There are several “stories” of drug experiences and communications with others interested in the use of psychedelics but the most important part of Book 1 is the section on naturally occurring DMT (N, N-Dimethyltriptamine) and its analogues. This long section details where DMT is found in nature and how it can be extracted from common plants, thereby putting it within reach of people who otherwise have no access to the chemicals needed to synthesise the other compounds found in the two books. DMT is an extremely potent and short lasting hallucinogen, when administered intravenously or intramuscularly, or when smoked. As Nicholas Saunders puts it in his preface “...the means for psychedelic exploration can never be controlled again. The genie is out of the bottle and all the king’s horses and all the king’s men cannot put it back again”.[66] What made Alexander Shulgin let the genie out of the bottle? His belief that psychedelics should be legalised is obviously the driving force behind the publication of TIHKAL, but it could be suggested that the contents of TIHKAL might have gone unpublished for several years if the DEA had not been so heavy handed in its clampdown on the lab of Dr. Shulgin. The book can be seen as a retaliation to the DEA, a direct attempt to strike back in the only way they knew how.

           

 

The Renewal of Legal Human Experimentation

            The last five to ten years have seen a slow change in the attitudes of governments and the public to the use of psychedelics in medical and scientific research. In the United States, applications for grants for psychedelic research with human subjects have been made and granted, most notably work on DMT and psilocybin. Several organisations now exist to promote research into psychedelics, offering grants and a forum for results to be presented. The foremost of these are MAPS (Multidisciplinary Association for Psychedelic Studies) and the Hefter Institute.

            Several factors were involved in the renewal of human based studies of psychedelics in the United States in the early 1990s:

            (1) Changes in science and technology: A huge amount of data from animal studies had been collected, and it was recognised by researchers that human studies were needed to allow this data to be useful for human pharmacology. Also, advances in technology and molecular biology played an important part. The development of PET (Positron Emission Tomography) and MRI (Magnetic Resonance Imaging) scanning meant that the sites of action of hallucinogens in the brain could be studied.[67] At first, retrospective studies of the effects of long term use on the brain were the focus of research, as this work could be done without having to give subjects controlled drugs, by getting drug users to volunteer for study.[68] This avoided all the bureaucratic difficulties and opposition that actually giving controlled drugs to a subject entailed. Advances in molecular biology meant that much more was understood about the normal functioning of neurotransmitters in the brain.

            (2) Changes in political attitudes: A conscious change in the attitude of the FDA also took place at the beginning of the decade. Curtis Wright, deputy director of the FDA Division of Anaesthetic, Critical Care and Addiction Drugs, explains why: “[In] the 1960s and 70s, the FDA’s role with respect to drugs of abuse was very conservative. [The] FDA was seen as protecting the culture from those who would use the drugs improperly...all protocols involving drugs of abuse went through the FDA’s Drug Abuse Advisory Committee...we...didn’t know what the long-term danger from exposure to these agents [hallucinogenic drugs] were...So there was a tremendous amount of conservatism about allowing research with hallucinogenic drugs except under very careful control...the process [of approving a protocol] was very onerous and lengthy.”[69] However, in the 1990s, questions began to be asked if whether hallucinogenic drugs and drugs of abuse should not be treated in the same way as other potentially dangerous drugs: “the agency was challenged legally in a number of cases and also underwent a process of introspection, asking Is it proper to treat this class of drugs differently?...we were fortunate enough to have the NIDA (National Institute on Drug Abuse, a government funding agency) challenge the FDA to do a better job...the conclusion was that the FDA was going to treat all drugs the same...the deputy director wrote...a statement that we were going to treat [hallucinogens, marijuana, and other drugs of abuse] no differently than any other [drug].”[70] This was in 1994, and this has been the FDA’s official policy ever since.

            (3) The final, and perhaps the most important factor, was the catalyst of one man with enough determination and perseverance to push the first human based study though the application and approval process.

            The first legal studies of the action of hallucinogens in humans since the 1970’s were conducted by Dr. Rick Strassman in 1991 at the University of New Mexico.[71] The study carried out by Strassman and his colleagues was not into LSD, nor the “designer drugs” (like MDMA) that Shulgin and others like him had been investigating in the 1980’s. Rather, they chose a comparatively unknown compound, DMT (see the previous section). The reasons for choosing this drug as opposed to the “classic” psychedelics are detailed in the article published as a result of the experiments and in a second article written by Strassman describing the application process for federal approval of their studies.[72] The reasons for choosing DMT fall into different categories:

 

            “Scientific” reasons - DMT is present in small amounts in healthy humans, and it was considered in the 1960s and 1970s to be a possible endogenous toxin which might cause schizophrenia, and Strassman argued that an understanding of the action of DMT might help increase understanding of the possible action of schizophrenia.[73]

 

            Political reasons - DMT is a relatively obscure drug, without any of the troublesome social history of LSD and psilocybin. This may have made the study more palatable to the authorities who would have been less likely to approve a study with a more widely abused drug. This factor also has the additional effect of generating less expectations in the subjects of the drug’s effect, because of its obscurity.

 

            Practical reasons - The short duration of the drugs effect (approximately 30 minutes when delivered intravenously) makes it easier to use in a clinical situation than longer acting hallucinogens. Reactions in the potentially stressful environment of the clinic would be minimised.[74]

 

            The experiments were crucial not just for their scientific value, which was large, as no-one had conducted detailed studies of the physiological effects of DMT on humans before, but also for their political value as a test case for drugs research approval. It took Strassman two years to wade through the bureaucracy before he was given the go ahead. He faced several major hurdles: the IRB (Institutional Review Board) was concerned how he could justify giving a Schedule I drug which by definition had “no medical value” and cannot be used safely, even under medical supervision, to subjects. They wanted him to include a statement on the consent forms that DMT was a Schedule I drug with no medical value. Strassman successfully argued that the drug had no current medical value, and was able to eventually remove the statement from the form altogether by saying that if the FDA approved his study then they would be accepting the fact that DMT had some possible medical value.[75]

            Another problem he faced was having to find a supply of high purity DMT fit for human consumption. The supplies of the drug available from chemical companies were all lab-grade i.e. not intended for human delivery. Finding a source of clinical-grade DMT was a major problem and Strassman says “at one point in time I began to fear that the whole project would come to a dead end because satisfactory DMT could not be obtained”.[76] Eventually, Strassman was able to find a colleague with “experience in synthesis of hallucinogens within a university setting”[77] who was willing to make DMT to the specifications imposed by the FDA.

            At the end of the process of gaining FDA and DEA approval, Strassman showed that it is possible to get permission to study Schedule I psychedelics in humans, with perseverance, and he stressed the following points:[78]

            (1) A scientifically well reasoned experimental design and protocol is essential.

            (2) Funding from outside agencies increases the credibility of the application (in this case, funding was given by the Scottish Rite Foundation for Schizophrenia Research and the National Institute on Drug Abuse).

            (3) A collaboration with someone who can manufacture the required drugs may be necessary, and drug companies may not be able to provide the substances required at high enough purity for a reasonable price.

 

            After the success of Strassman’s application, the door was open for further human experimentation with psychedelic drugs. The major hurdle now associated with conducting psychedelic research was funding - the FDA were more willing to accept protocols for psychedelic research, but few government funding agencies were willing to put money into such scientific work. Pharmaceutical companies were also cautious about supplying money, partly because of the negative image of psychedelics, but also for economic reasons. Most of the classic hallucinogens have been around for a long time, and many of the drugs perceived as being more “modern” (e.g. MDMA and MDA) were first discovered and patented at the beginning of the century. Once a drug has been patented once, it cannot be patented again, so there is little financial incentive for the pharmaceutical companies as they will not hold any control over any already well known drugs they develop. So the two mainstays of research funding were unwilling to contribute: the government because of a reluctance to sponsor psychedelic research not aimed at addiction studies; and the industry because of a lack of financial incentive. So In 1986 MAPS, the Multidisciplinary Association for Psychedelic Studies, was founded by Rick Doblin, with the aim of providing an alternative source of funds. MAPS “is a membership-based non-profit research and educational organisation. We assist scientists to design, obtain approval for, fund, conduct and report on research into the healing and spiritual potentials of psychedelics and marijuana...MAPS has disbursed over a quarter of a million dollars to worthy research projects since 1990”.[79] The money has been spent on a wide range of studies into a wide range of drugs, including MDMA, DMT, psilocybin, ibogaine, ketamine and LSD. Studies include psychobiological and neurotoxicity research, as well as psychedelic assisted psychotherapy. There have also been some important long-term follow-up studies of LSD therapy from the 1960s, an area that received little attention at the time of the original experiments, but which is crucial for demonstrating the effects of the therapy. These various studies have been, and are being carried out around the world: psychotherapy and treatment of heroin addicts with ketamine in Russia, psychotherapy with MDMA in Switzerland, pharmacokinetic and neurotoxicity studies of MDMA in the USA, treatment of cocaine addicts with ibogaine in the USA and Israel.[80] Another non-profit body which funds scientific psychedelic studies is the Heffter Institute, set up in 1993, which has also funded a number of completed and ongoing studies.[81]

            Changing attitudes can also be seen in the public attitude towards psychedelics: in 1997 the BBC screened a Horizon program on the renewal of psychedelics research in the U.S., which painted it in a positive light.[82] They interviewed all the important figures, both researchers who had been active during the 1960s and those who have been conducting studies in more recent times, including Abram Hoffer and Rick Strassman. The program concludes that such research has the potential to help people in various ways, but also warns that researchers must avoid the situation that developed in the ‘60s - “you can’t get too close to these substances...they’re not to be used in a recreational way. They cannot be used outside of established medical centres. That was the mistake of the ‘60s”.[83] Interestingly, the program talked about LSD, ayahuasca, DMT and ibogaine, but failed to mention MDMA entirely. Charles Grob, one of the researchers interviewed had done extensive work with MDMA, but only his study of ayahuasca, a plant source of DMT, was mentioned. Dr. Jansen of the Institute of Psychiatry in London, who has conducted studies involving MDMA and ketamine, believes that the high political profile of MDMA in this country as a drug of abuse meant that the programmers had to leave it out, for fear of the negative press it would generate[84]

 

The Future of Psychedelic Research

            Drugs intended for medical use go through three distinct phases in their development: Phase I is the study of basic biological and physical effects, including adverse reactions. Phase II involves giving the new drug to small groups of patients with a particular disease. Phase III consists of large scale projects with many test subjects. After that, the drug is submitted to the appropriate administrative body (the FDA in the United States) for permission to sell the drug to treat certain disorders.

            Psychedelic drugs appear to be in the first phase of development.[85] There are several areas which can be identified as requiring further study:

            Psychopharmacology - Further studies of the action of psychedelics on neurotransmitters, and further studies involving brain-scanning (i.e. PET and MRI). Such studies would provide a more detailed description of how such drugs work in the brain.

            Ethnopharmacology: - There are a large number of plants used traditionally in many different cultures around the world, which have claimed psychedelic properties. Scientific study of these plants may reveal new and unusual psychoactive compounds. An example of such work that has already happened is the isolation of Salvinorin-A from the plant Salvia Divinorum. This is of particular interest, since it is not an alkaloid, like most of the naturally occurring hallucinogens.

            Psychotherapy: - The development of a standard protocol for psychedelically assisted psychotherapy. Many researchers feel that the best way to do this would be to combine elements of psychedelic therapy with elements of psycholytic therapy.[86]

            Cognitive Psychology: - The development of a cognitive theory of psychedelic action would allow the two current branches of research, the pharmacological and the psychological, to achieve an area of interaction, as has happened in other fields of mainstream psychology, such as abnormal psychology.

            It is unclear how the study of psychedelics will progress beyond such Phase I research, and it will probably not do so in the near future. Some of the major claimed applications of psychedelics are as aids to creativity and religious practice, and the use of drugs in this way is traditionally frowned upon in western culture. The likely outcome is that psychedelics will be used to treat alcoholics and other drug addicts, once protocols have been established, but the use of psychedelics in a non-medical but non-recreational way, certainly in western culture, is along way off.

 

 

 

 

PART TWO: The Sociology of Psychedelic Research

 

            The field of psychedelic studies has changed since its beginnings in the 1950s. This section will explain the changes that have occurred, in methodology and approach and show that the way in which the science is conducted is determined by the wider social and political interests of the scientists involved. The differences will be analysed in terms of the changes in “evidential culture”, the public political views of the sciences involved, and the approaches to the unique problems of methodology and ethics that the field presents. It will then be shown that the reasons for these changes of approach are all attempts to distance the modern field from the field of the 1960s, whilst using some of the basic assumptions from that period, and the overall aim of current researchers is to solve the problems of methodology and ethics in a scientifically acceptable way.

 

Evidential Cultures in Psychedelics

            To look at the way the methodology and style of psychedelic studies have changed since the 1960s, it is helpful to refer to Harry Collins’ model of “evidential cultures”. In his theory, Collins identifies three dimensions of evidential culture: “evidential collectivism” versus “evidential individualism”; high versus low evidential significance; and high versus low evidential thresholds.[87]

            Evidential collectivism is the belief that the responsibility for assessing the integrity of the results is the job of the larger scientific community. Evidential individualism, on the other hand, is the belief that it is the responsibility of the individual, or the individual team or lab, to ensure that their data is valid.[88] High evidential significance means reporting statistical data as real phenomena; low evidential significance means reporting data with little real significance: in Collins’ example, this involves reporting seeing “gravity waves” on the one hand, or simply seeing statistical “coincidences”, with no theoretical claims.[89] In psychedelic science, this might be reporting that “X% of subjects had a transcendental experience, leading to their recovery” instead of just reporting the statistics without offering any judgement. High evidential significance leads to high “interpretative risk” - there is more chance of attracting opposition and more ways of being wrong, whereas low evidential significance is a much more “safe bet” - the “interpretative risk” is much lower.[90]

            The final dimension of evidential culture, identified by Collins, is the evidential threshold. This is simply the level at which results are considered as significant - Collins notes that this can be simply a matter of the rigorousness of the statistics: “social sciences have a low evidential threshold while high-energy physics has a high evidential threshold”.[91]

            The three dimensions together characterise a science, or a specific school within a science, as having a more “open” or “closed” evidential culture. An open evidential culture has a high degree of collectivism, low significance and low threshold. A closed culture has a high degree of individualism, high significance and high threshold. It is important to stress that not all the members of an overtly open or closed culture will individually share all these beliefs about the way their evidence should be presented.[92]

            How does this model apply to psychedelic science? In Collin’s article, there is a geographical separation between the two different cultures. The team from Frascati has a more open-type culture, and the Louisiana team a more closed one (both groups are studying gravitational waves). In the psychedelic sciences, the separation is a temporal one: the early period (1950s-1960s) shows characteristics of an open culture, whilst the more modern period (1990-the present) is a more closed type culture. The next few paragraphs will explain the changes in the different dimensions of the evidential culture.

            In the early period of psychedelic studies, the field was at first one in which a philosophy of evidential collectivism was prevalent. Many individuals were conducting experiments without much theoretical basis, and getting their results published. Because of a lack of a coherent theory within the field as a whole (the contrast between the psycholytic and psychedelic paradigms), the evidential significance of the published results was low - Hoffer and Osmond often said that they were getting good results with their alcoholic patients (around 50-70% cured), but they didn’t know why.[93] There was a great deal of speculation, and over time the evidential significance grew, with different researchers beginning to give their results psychological explanations.

            Looking at the modern status of the field, it is clear that the culture in place today is a much more closed type culture. The responsibility lies with the experimenter to provide good data, and the demand is for higher evidential significance and higher evidential threshold. This move towards a closed culture is linked with the perceived public view of the psychedelic sciences: there is a strong desire to make the presented experimental work appear as scientific and rigorous as possible. The period of the ‘60s is associated with a very negative image of psychedelics, and the modern researchers wish to distance themselves from it as much as possible. In particular, a more closed culture puts the responsibility in the hands of the individual scientists, which encourages more rigorous controls and experimental attitude than that seen in an open culture.

 

The Politics and De-Politicising of psychedelics research

            Psychedelic drugs have been highly politicised in the past, with researchers commonly taking a pro-drug, pro-legalisation stance and the government taking a conservative, anti-drug view. Since the early 1990s, there has been a move on both sides to move away from their traditional standpoints and to concentrate on sound scientific research. Modern researchers take a much more neutral stance, realising that such views alienate parts of their potential audience. The audience for published work on psychedelic drugs is large, larger than the audiences for many other sciences: it includes not just the scientists involved in the field and the medical community, but also politicians, drug users, parents, and teachers. Instead of promoting the chemicals they study for recreational use, in the way Leary and Alpert did in the ‘60s, their aim is to promote their science. In particular, some researchers have emphasised the importance of publishing results of experiments which show psychedelics in a negative light, instead of sweeping them under the rug,[94] to prove to the general science community, the government and the general public that they are putting science foremost and are not on any kind of political crusade. The government’s change of stance was noted previously in the last section, where Curtis Wright of the FDA explained that there has been a conscious move to treat psychedelics in exactly the same way as other drugs.

            One example of the politicisation of psychedelics is the politics of scheduling. In the US, illegal drugs belong to different schedules, Schedule I being the most restrictive. By definition, a Schedule I drug is a drug of abuse with no medical value. Drugs can change Schedule: as an example, THC was reclassified from Schedule I to Schedule II when it was shown to have medical uses, such as appetite stimulation in anorexia. During the 1970s and ‘80s, the apparent policy of the U.S. government was to Schedule drugs not on the basis of safety considerations, but rather whether they were “abused” i.e. used recreationally. An example of this is the scheduling of AET, a tryptamine derivative. AET was scheduled because it was being sold and used recreationally, but its sister compound, AMT, which is also psychedelic remains off the schedule simply because it has not been as popular as a recreational drug.[95]

            The introduction of the Controlled Substances Analogue Enforcement Act at this time shows the attitude of the government: these laws made drugs illegal on the basis of their qualitative effect - not on the basis of whether they were dangerous or drugs of abuse. This leglislation is thus an attempt to exercise social control, to stop people using drugs to produce altered mind states for recreational purposes, whether or not it is actually detrimental to health.

 

Methodology of Psychedelics Research

            Studies done into the psychological effects of psychedelic drugs present interesting problems not present in mainstream science or in animal studies of psychedelic drugs. These problems centre around the subjective nature of the psychedelic experience. The problems encountered in psychological research of the intrinsic unrepeatability of certain experiments is here multiplied many times over: the effect of any hallucinogenic drug not only varies widely from person to person, but is extremely dependant on the “Set and Setting” of the user. Several different approaches have been taken to this problem. In the therapy of the ‘50s and ‘60s, there was little attempt at all to quantify the psychedelic experience, either subjectively or objectively. Scientists such as Abram and Hoffer seemed content to know that LSD could produce a wide range of effects, and the only distinction made was that between the low dose experience used in psycholytic therapy, and the high dose “peak experience” that was characteristic of psychedelic therapy. Others, such as Leary and Alpert tried to investigate the psychedelic state, but abandoned science to use a religious or mystical model to describe the effects they were seeing.

            Shulgin takes a different approach. He claims to totally abandon any idea of objectivity as unobtainable, but describes a method of quantifying the subjective experience of the individual, to allow some degree of objective comparison.

            He describes his method of working in the introduction of “PIHKAL”.[96] His starting assumption is that the pharmacological action in man, and thus its psychological effect, of any new chemical is unknown until it is tested in man. His method of assaying is to ingest a sample of a newly developed drug at “10 to 50 time less, by weight, than the active level of its closest analogue. If I have any doubts, I go down by a factor of 10 again”.[97] Once this level has been tested and produces no observable effect, he increases the dose “on alternate days, in increments of about a factor of times two at low levels, and perhaps times one and a half at higher levels”. To reduce the possibility of tolerance developing, no drug is repeated on sequential days, even if there is no observed effect. Shulgin develops his own qualitative scale for drug effects, which ranges in five stages from (-) to (++++).

            “(-) or minus. There is no effect noted, of any nature, which can be ascribed to the drug in question. This condition is also called “baseline”, which is my normal state.

            (±) or Plus-minus. I am feeling a move off baseline, but I can’t be absolutely sure it’s a drug effect...

            (+) or Plus-one. There is a real effect, and I can track the duration of that effect, but I can’t tell anything about the nature of the experience...early physical signs, if they arise at all, usually dissipate within the first hour, but they must be considered real, not imaginary...

            (++) or Plus-two. The effect of the drug is unmistakable, and not only can its duration be perceived, so can its nature. It’s at this level that first attempts at classification are made, and my notes might read something like this “there is considerable visual enhancement and much tactile sensitivity, despite a light anaesthesia.”...

            (+++) or Plus-three. This is the maximum intensity of drug effect. The full potential of the drug is realised. Its character can be fully appreciated (assuming amnesia is not one of its properties) and it is possible to define the chronological pattern exactly...

            (++++) or Plus-four. This is a separate and very special category, in a class by itself. The four pluses do not imply that it is more than, or comparable to, a plus-three...”[98]

            These ratings are not only used to give some scale to the maximum level of a drugs effect, but are also a series of stages through which the subject progresses. The reports in PIHKAL and TIHKAL might say “plus-one achieved after one hour, which moved smoothly to a plus-two by the third hour, which was maintained until the comedown period, five hours after ingestion”. Shulgin them goes on to discuss the problem of objectivity, or lack of it inherent in such testing. He first says that measurements of the drug’s effect should be ideally objective but “in the case of drugs like these - psychoactive drugs - the effects can be seen only within the subject’s sensorium. Only he can observe and report the degree and nature of the drug’s action. Hence, the subject is the observer and objectivity in the classic sense is impossible”.[99] This raises the question of whether such experimentation has any place in science at all: since objectivity and repeatability are both impossible, according to Shulgin, and these are two of the most important principles in science.

            Dr. Strassman has taken a different approach. In his pioneering study of the physiological and subjective effects of DMT, he created a device which he named the Hallucinogen Rating Scale. This is a questionnaire, which was initially developed by asking experienced DMT users in interview what the experience of what the drug was like.[100] The questionnaire was then tested and modified in an experimental situation: it was given to 13 subjects given a low dose and to 12 subjects receiving a high dose, non-blind. The end result is a series of 100 questions which are given to the subject immediately after the drug experience (the DMT experience is too intense to allow subjects to fill in the questionnaire whilst under it’s influence). The 100 questions fall into five clusters After data was collected from the 11 experienced users whom took part in the double-blind, placebo controlled study it was found that the HRS score showed statistically significant discriminations between different doses of the chosen drug, DMT. In their experiments, Strassman found that the HRS was a much better discriminator between different levels of the drug than all the detailed physical data they had recorded from their subjects.[101] Since then, the HRS has been adapted for other drugs (including LSD and psilocybin) and translated into several languages and is fast becoming a standard in the field.

            Both these methods rely on a degree of trust between experimenter and subject, of which is another area of debate in the sociology of scientific knowledge.

 

Trust and Testimony

            The question of trust in science in general is an important one: in many cases, if not all, science is done in teams, from small groups in the lab to the worldwide community of a scientific discipline. To claim knowledge of a particular field requires implicit trust of ones fellow scientists - a particle physicist may claim to “know” a lot about his field, but he could never perform all the experiments himself that his subject is founded on. Rather, he relies on texts and the published work of other physicists - whom he trusts.[102] Here, as in some fields of psychology, the experimenter must trust his subjects to report clearly their subjective experience. This can have an obvious influence on the choice of subjects. Both Strassman and Shulgin rely on experienced hallucinogen users as there test groups, trusting that they will give an accurate report. For an unexperienced user, the psychedelic effect, especially of the stronger drugs, such as DMT, may be to much to allow detailed reporting. Experienced users can also compare and contrast different drug experiences which may be helpful to the researcher.

            The objection could be raised that experienced users would probably have a political pro-drug stance, and stand to gain from any loosening of the restrictions on drug control laws. Thus, they might be more likely to produce favourable reports of the experimental experience if they thought it would lead to some eventual change in the law. However, it could be countered that the experience produced by high doses of LSD or DMT is so powerful that false reporting becomes almost impossible. Descriptions of such doses of describe the experience as life-changing or spiritual, with deep meaning,[103] which would suggest that some serious motivation would be required to describe the experience in any other way.

            Mainstream scientists might not look at it in this light. The negative image that drug users have would probably not inspire confidence in their fidelity. A way around this might be to conduct studies with academic scientists as subjects: their drug naivety would perhaps be offset with their desire for truthful reporting and analytic attitude.

            This kind of statistical tool gives more scientific credibility to the experiments than the mystical explanations of the psychedelic experience that predominated in the 1960s.

 

Blinds, Experience and Ethics

            One important dilemma that is encountered in the study of psychedelic drugs in humans is the balance between treating subjects ethically and the desire to obtain the most useful information. For many studies, the best possible experimental method would be to use large samples of drug naive subjects, especially for research into what changes occur in the brain, if any, from a single drug experience. However, this kind of study is widely regarded as being unethical. The issue of debate is the necessity of getting the informed consent of the subjects participating in a trial, and this is perceived as being difficult, if not impossible for drug naive subjects. It is impossible to establish any kind of “informed consent” since the variety of possible experiences and effects of such drugs are manifold, and almost impossible to describe to someone who has no experience of altered states of consciousness.

            This has been the view for quite some time, and indeed in many cases it still is. However, some studies are being conducted at the moment which use drug naive subjects.[104] These studies are necessary to determine the what changes occur in the brain from a single use of a drug, but some might say they are ethically unsound. The studies involve MDMA, which produces a much less overwhelming experience than DMT or LSD, so there is less concern about adverse reactions to the drug. Rather, it has been shown that MDMA causes some neurotoxic effects in rats, and it seems ethically dubious to give a subject a drug which may have neurotoxic effects and no current medical application. In this kind of case, it is crucial that the doses administered are carefully controlled to minimise the risk to the subjects, and the subjects must be informed of any possiblity of long term effect.

            Another question of methodology is the value of blind studies. Shulgin believes that blind studies have no value - the effects of the drug are so obvious as to alert the subject. In some situations this could be detrimental, for instance in Pahnke’s Good Friday experiment.[105] In this study, psilocybin was given to a group of theology students, whilst another group received a niacin placebo, and both groups attended the same Good Friday service. The aim of the study was to see if the psychedelic could induce a genuine religious experience, but it was a failure because it was quickly obvious to the students which of them had had the psilocybin, and this coloured their reports.[106]

            However, most modern research includes controlled blind studies (e.g. Strassman’s DMT study), where the subjects do not observe each other, unlike in Pahnke’s experiment. Again, the reasoning here is to make the experiments scientifically acceptable. Blind studies are a requirement for most psychological research, so psychedelics research must use them too if it wishes to appear credible in the eyes of other scientists.

 

Conclusions

            The conclusions of this study are twofold:

            Firstly, a study of the history of psychedelic research has shown that the field showed much promise at its early stages in the 1950s, but was effectively stopped in the 1960s and ‘70s by legislation. This clampdown was caused by social concerns, rather than any medical problems associated with LSD and other psychedelics. However, part of the blame can be layed on scientists who encouraged the spread of recreational use.

            Subsequently, human based research was only able to begin again after a change in the attitude of governmental bodies and after Strassman showed it was possible to conduct such research safely in a controlled environment.

            Secondly, the overall strategy of modern psychedelics researchers is to distance themselves from the older style of working as practised in the 1950s and ‘60s, whilst at the same time acknowledging the pioneering work done in this period. This can be seen in the three areas above: there has been a movement towards a more closed evidential culture with its emphasis on the scientific responsibility of the individual; a conscious attempt to de-politicise the science from both researchers and government figures; and attempts to tackle the problems of methodology and ethics in a scientifically accepted way.

            The study of psychedelic drugs has much to offer science: they may help us understand how the biochemical processes of the brain work, and how they differ between normal individuals and those with conditions such as schizophrenia and psychosis. They may also prove to be useful as adjuncts to psychotherapy and to help cure drug addiction of many forms.

            However, scientists must be careful to avoid the mistakes made in the 1960s which led to the twenty year moratorium on such research and generated much fear and hysteria about the dangers of psychedelic drugs, both medical and moral. There is some debate over whether individuals have a right to use such substances recreationally or as part of religious practice - such questions fall outside the scope of this project, but if scientists wish to be able to continue research into psychedelic drugs they must, at least for the foreseeable future, keep psychedelics well within the realm of science and medicine.

 

 

 

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[1] Stevens [1987] p.57

[2] Grinspoon and Bakalar [1979] p.9

[3] Ibid. p.29-30

[4] Strassman [1995] p.127

[5] Wasson [1957] p.275-286]

[6] Stevens [1987] p.5-6

[7] Hofmann [1983] Ch.1 and Hofmann [1994] p.7-16

[8] Ibid. p.13

[9] Hofmann [1983] Ch.4 and Stevens [1987] p.11

[10] Homann [1983] Ch.4

[11] Yensen [1985] p.267

[12] As cited in ibid..

[13] Ibid. p.268

[14] Ibid. p.268

[15] Hollister [1962] p.81

[16] Pellerin [1998] p.49-55, Stevens [1987] p.79-84 and Wilner [1995] p.23-25

[17] Stevens [1987] p.81

[18] Pellerin [1998] p.54

[19] Leuner [1967] p.101

[20] Sandison [1997] p.60

[21] Caldwell [1968] p.121

[22] Yensen [1985] p.268

[23] Ibid. p.269

[24] Sandison [1997] p.60-61

[25] Buckman [1967] p.86

[26] Caldwell [1968] p.117-118

[27] Abram Hoffer, quoted in Pellerin [1998] p.46

[28] Yensen [1985] p.270

[29] BBC [1997]

[30] Ibid..

[31] Stevens [1987] p.74-77

[32] Grinspoon and Bakalar [1979] p.17

[33] Novak [1997] p.99

[34] Cohen and Ditman [1962]

[35] Cohen [1960]

[36] Novak [1997] p.107-108

[37] Ibid. p.109

[38] Shulgin and Shulgin [1997] p.593

[39] Novak [1997] and Novak [1998]

[40] Cohen and Ditman [1962]

[41] Stevens [1987] p.278

[42] Congressional Hearings, as cited in ibid. p.279

[43] Cohen [1960] p.39

[44] Novak [1997] p.107

[45] Stevens [1987] p.181

[46] Cohen and Ditman [1962] p.182

[47] Richter [1994] p.208-210

[48] Pellerin [1997] p.79

[49] Sewick [1997] Ch.3

[50] Sandison [1997] p.74

[51] Ibid..

[52] Sewick [1997] Ch.3

[53] Shulgin and Shulgin [1991] p.18

[54] Ibid. p19-21

[55] Ibid. p.22-25

[56] Ibid. p.41

[57] Ibid. p.42

[58] Ibid. p.xxxvi

[59] Stevens [1987] p.357-366

[60] Shulgin [1986] p.300

[61] Covered in detail in Shulgin and Shulgin [1997] p.437-441 and p.349-352

[62] Shulgin and Shulgin [1997] p.3

[63] Ibid. p.7-18

[64] Ibid. p.20-34

[65] Ibid. p.34-38

[66] Ibid. p.xvi-xvii

[67] Pellerin [1998] p.97

[68] Jansen [1996]

[69] From an interview, quoted in Pellerin [1998] p.162-168

[70] Ibid.

[71] Strassman et al. [1994]

[72] Strassman [1991]

[73] Ibid. p.30

[74] Strassman et al. [1994] p.88

[75] Strassman [1991] p.31-32

[76] Ibid. p.35

[77] Ibid. p.36

[78] Ibid. p.37-38

[79] MAPS [1999]

[80] MAPS [1999a]

[81] Pellerin [1998] p.175

[82] BBC [1997]

[83] Curtis Wright in BBC [1997]

[84] Jansen [1997]

[85] Strassman [1997] p.155

[86] Yensen [1985]

[87] Collins [1998]

[88] Ibid.

[89] Ibid.

[90] Ibid.

[91] Ibid.

[92] Ibid.

[93] Stevens [1987] p.86

[94] MAPS [1995]

[95] Shulgin and Shulgin [1997] p.437-441

[96] Shulgin and Shulgin [1991] p.xx-xxviii

[97] Ibid. p.xxii

[98] Ibid. p.xxiv-xxvi

[99] Ibid. p.xxvi

[100] Appendix to Strassman et al. [1994]

[101] Ibid.

[102] Hardwig [1985] and Hardwig [1991]

[103] Strassman [1997] p.157

[104]  Gamma and Vollenweider [1998]

[105] Pahnke [1963]


[106] Yensen [1985] p.273