In addition to the action of tryptamines on serotonin receptors, there may be indirect effects of psilocybin on dopamine receptors as well. Some people speculate that dopamine is the neurotransmitter most involved in the experience of pleasure—for example, the “rush” of a cocaine high. The interaction with dopamine may account for some of the intense erotic-ecstatic sensations and feelings that can be part of the psilocybe mushroom effect.
Examination of the structural formulae of the entheogenic and endogenous tryptamines reveals striking similarities and parallels, which are suggestive of systemic interactive effects, though they do not prove them. The basic core molecule, tryptamine, consists of an indole ring and an amine side chain. It is biosynthesized in the body from nutritional tryptophan, one of the essential amino acids. Serotonin is 5-hydroxy-tryptamine (5HT), the tryptamine molecule with a hydroxy molecule in the 5-position. Serotonin itself cannot be absorbed via ingestion as it does not pass the “blood-brain barrier.” It is synthesized in the brain (probably the pituitary and pineal glands) from tryptophan via the intermediate step of 5-hydroxy-tryptophan (5HTP). Both tryptophan and 5HTP can be absorbed orally and act to increase serotonin levels in the brain; both have been and are used in the treatment of depression. Numerous studies link depression, as well as anger, insomnia, and addictive cravings, to serotonin deficiency (Murray 1998), which is treatable with 5HTP. The well-known pharmaceutical creations known as the SSRIs (such as Prozac, Zoloft, and others) also act to increase the amount of serotonin at the synapses, but they do this by selectively inhibiting the “re-uptake” of serotonin, thus preventing its storage making it more available at the synapse.
When a double methyl group is added to the tryptamine molecule we have dimethyltryptamine (DMT), an extremely powerful hallucinogen that is found in several shamanic entheogenic plant preparations and endogenously in the human brain. DMT is synthesized in the brain’s pineal gland. Some have speculated that DMT or one of its derivatives might be responsible for the vivid imagery of dreams and spontaneous visions. Dr. Rick Strassman, who completed an extensive psychiatric research project with DMT, calls it the “Spirit Molecule” and suggests that pineal-produced DMT is released in near-death experiences and other mystical revelations (Strassman 2001).
Psilocybin, the psychoactive principle in psilocybe mushrooms, is fairly rapidly changed into psilocin after oral ingestion, making the latter the active hallucinogen. Psilocin is 4-hydroxy DMT, i.e., DMT with an additional hydroxy molecule at the 4-position. Physiologically, psilocin (and psilocybin and the mushrooms) produces moderately intense sympathetic nervous system activation within 30 minutes of ingestion, lasting for about 3–6 hours, depending on dosage. The most easily observable autonomic effects include pupil dilation and transient variations in heart rate and blood pressure. Researchers agree that these physiological changes are insignificant in comparison to the vivid perceptual, cognitive, and affective changes (Passie et al. 2002). Perceptual changes are of the kind typically found with other tryptamine hallucinogens, including DMT and ayahuasca: enhancement of all sensory modalities, synaesthesias, brightly colored kaleidoscopic visuals behind closed eyelids, perception of interconnected webs and lattices of energy patterns that seem to be full of spiritual and psychological meaning as well as visually gorgeous.
Although the focus of this book is on psilocybin and psilocin (and the mushrooms that contain these molecules), for the sake of comparison I will mention two other tryptamine derivatives that are of great interest for the understanding of the relationship between molecular structure and psychoactivity. If the hydroxy molecule is at the 5-position, we have 5-hydroxy-DMT, or bufotenine, which is the main toxic ingredient in the exudates of many species of toads (Latin: bufo). Largely because of this structural similarity to DMT and psilocybin, bufotenine was placed on Schedule I during the prohibitionist frenzy of the midsixties, when LSD was also illegalized. Scientific researchers in the field however had never found any evidence to support its psychoactivity, and toad venoms are generally regarded as toxic rather than hallucinogenic (although they have found occasional use as homeopathic medicines). Very recent research by Manuel Torres, Jonathan Ott, and Christian Rätsch, has however established that among the Wichi of Southern Argentina, the ground seeds of Anadenanthera colubrina, known as cebil, are smoked or snuffed for shamanic divination; and the main psychoactive ingredient in cebil is bufotenine! (Ott 2001).
If a methoxy molecule (instead of hydroxy) is substituted at the 5-position with DMT, we have 5-methoxy-DMT, or 5-meo-DMT, a substance as equally powerful as DMT, but more potent, i.e., the same effect is produced by a much smaller dose. This tryptamine derivative is the main psychoactive ingredient in shamanic snuffs, variously known as cohoba, yopo, epena, and other names, derived from two South American plant sources. These snuff materials have a long documented history of indigenous shamanic use: snuff trays and still viable seeds have been found in burial sites dated to 1500 B.C.E in the Atacama Desert of northern Chile. Also 5-meo-DMT is the psychoactive ingredient in the exudate of one species of toad, the Colorado River toad, that does have hallucinogenic effects—though no shamanic use of this animal hallucinogen is known to date (Ott 2001).
In the introduction to the ayahuasca book I pointed out that two analogies or metaphors for the drug experience have been repeatedly used by writers in both the psycholytic and psychedelic paradigms. One is the amplifier analogy, according to which the drug functions as a nonspecific amplifier of perception of both inner and outer stimuli. This is the “cleansing of the doors of perception” of which William Blake wrote in his poetry, and which Aldous Huxley used to describe his first visionary experiences with mescaline. The other analogy is the microscope metaphor. It has been repeatedly said that psychedelics could play the same role in psychology as the microscope does in biology: opening up realms and processes in the human mind to direct, repeatable, verifiable observation that have hitherto been largely hidden or inaccessible. Both amplifier and microscope are technological metaphors for expanded perception and divination—the ability to see and hear more vividly, to see into other, normally invisible worlds or dimensions, and to obtain otherwise hidden knowledge (Metzner 1999).
Both the amplifier and microscope analogies help us to understand how the “set and setting,” the internal expectations of the inner space voyager and the physical and social context of the voyage, act to determine the psychological content of the experience. This well-known relationship is amply documented in the experiential accounts in this book. When the set or intention is for healing of illness, as it was for most of the people who consulted Maria Sabina, then healings can take place; if people come looking for religious or spiritual insight or revelation, as was true for Wasson and many other seekers, then those kinds of mystical experiences can take place. In the naturalistic settings of the Harvard Psilocybin Project, described below, people had experiences of heightened self-awareness, interpersonal connection, and creative inspiration.
Psilocybin has been used as an adjunct to the therapeutic treatment of many psychological disorders, including anxiety, depression, sexual neuroses, obsessions, compulsions, and addictions. These studies are reviewed in the chapter by Torsten Passie. The two best-known application studies of psilocybin that came out of the Harvard Project—the Concord Prison study of rehabilitation, and the Good Friday study of religious experience—are also reviewed, with follow-up studies, in a separate chapter.
Let me return for a moment to the psychopharmacological hypothesis I ventured above—that the expansion of awareness induced by psychedelic tryptamines like psilocybin is a function of their raising levels of serotonin in key areas of the brain and nervous system. I had proposed (Metzner 1994) that one can regard transcendent experiences, as found in mysticism, as consciousness-expanding, and compulsive/addictive experiences as consciousness-contracting, fixating, and narrowing. It is then a natural step to explore the use of psychedelic substances in the treatment of compulsions and ad
dictions (Halpern 1996). Before it was banned, LSD was used in several different centers as a treatment for alcoholism. Participants in the Native American Church peyote rituals, and participants in the Brazilian churches that use ayahuasca as their sacrament, report a marked decrease in alcoholism. Iboga, an African hallucinogen, has been tested in the treatment of cocaine addiction. Psilocybin is currently being tested in the treatment of obsessive-compulsive disorders, as discussed in the chapter of this book by Rick Doblin, on current research projects.
TIMOTHY LEARY AND THE HARVARD PSILOCYBIN PROJECT
In 1959, two years after R. Gordon Wasson had published his groundbreaking account of a sacred mushroom ceremony in LIFE magazine, Timothy Leary, a Harvard University psychology professor, while on vacation in Mexico, was given an experience with the mushroom that changed his life dramatically, causing him to devote the rest of his career and his life to explore the potentials of these substances for the understanding of the human mind and their implications for society. Albert Hofmann had succeeded in identifying psilocybin as the active ingredient of the mushroom and the Swiss pharmaceutical company Sandoz, which had ten years earlier initiated experimental studies of LSD, also began to offer synthetic psilocybin to medical and psychological researchers. Thus it came about that psilocybin, the active ingredient of the Mexican hallucinogenic mushroom, was manufactured in tablet form by the Sandoz Company, which had a branch in New Jersey. They offered to supply the Harvard University professor with as much of the drug as he wanted, free of charge, for research purposes.
Thus begun the Harvard Psilocybin Project, which conducted studies of the psychedelic (“mind-manifesting”) drug with convicts, creative artists, religious professionals, and graduate students—of whom I was one. I signed on to assist with the study that was going to give psilocybin to convicts in Concord Prison. Since Leary believed that we all needed to be familiar with the experience ourselves before providing it to someone else, I had my first psychedelic experience (with psilocybin) in 1961 at the age of twenty-five, as part of Timothy Leary’s research project. Tim Leary’s account of his dramatic first experience with the Mexican mushroom, as well as my account of my first encounter with psilocybin while a graduate student at Harvard, are reprinted in this book.
The Harvard Psilocybin Project was formed to investigate, from a psychological point of view, the astonishing properties of this mushroom chemical. From the start, Tim Leary adopted what he called an “existential-transactional” approach to this research. He rejected the impersonal clinical atmosphere of the traditional psychiatric experiment. Having taken the substance himself in a sacramental atmosphere, he knew how important it was to have a warm supportive setting if one is to experience the ego-shattering revelations of the mushrooms safely.
We used the term “consciousness-expanding” for the drug and the experience; which is reminiscent of the “consciousness-raising” language of women’s liberation groups in the 1970s. This model was that if a safe, supportive set and setting is provided, with a small group of peers, the experience will probably be enlightening and productive. Another group of researchers in Menlo Park, California, including Willis Harman, Myron Stolaroff, Robert Mogar, James Fadiman, and others, were developing a creativity context for the drug experience: allowing for architects, artists, designers, scientists, and others to work on new problem-solving strategies during their session.
A similar attitude was adopted for the Concord Prison Project: rather than treating prisoners like guinea pigs in a lab experiment (as they too often are), we proposed providing them with insight-producing, “mind-manifesting,” experiences, in which we also participated. The intention and hope was that the men would gain sufficient insight to allow them to make the kinds of changes in their lives that would reduce the rate of return to prison after release. The results of this two-year study were mixed: on the one hand there were many profound experiences of insight and changes on personality tests; on the other hand, it quickly became clear that actually reducing the recidivism rate was a much more difficult and long-term challenge.
Aldous Huxley was at MIT in 1960 and became an advisor to the Harvard Psilocybin Project. In 1953 and 1955, Huxley had published two widely read books on his mystical experiences with mescaline, The Doors of Perception and Heaven and Hell. Huxley described the experience at its best as a “gratuitous grace,” providing access to what he called “Mind-at-Large,” beyond the “reducing valve” of the ordinary egoic mind. He and Leary developed a strong rapport and had psilocybin sessions together during that period, working out a nonclinical, supportive, yet objective and safe framework for this kind of experimentation. It was Huxley who gave Leary the idea of adapting the Tibetan Book of the Dead as a kind of manual for spiritually-oriented psychedelic experiences—death-and-rebirth were to be seen as a kind of metaphor for the ego-transcendence and subsequent return of the typical psychedelic experience. The religious dimensions of psychedelic experience were also reinforced for Leary through his association with Alan Watts and Huston Smith, both of whom became participants in some of the studies.
The religious mystical approach to psychedelic drug-experiences was developed further during the time of the Harvard project by Walter Pahnke’s epoch-making Good Friday Experiment, a carefully controlled scientific study of drug-induced religious experience. The set and setting of the experience were arranged to maximize the probability of religious experience: volunteer participants were students at a divinity seminary and the actual session took place in the basement chapel of a church where a Good Friday service with music and sermon was transmitted by speaker to the session room. The participants were divided into small groups, each with an experienced facilitator, and took either psilocybin or a placebo—with neither subject nor experimenter knowing who had which. Pahnke had culled a list of nine characteristics of mystical experience from the literature. He interviewed all subjects right after and a week after the experience. On all the criteria, the psilocybin group scored significantly higher than the placebo control group. In a twenty-five-year follow-up of this study, Rick Doblin found lasting impacts in many of the individuals who had participated in this study.
Gerald Heard, the distinguished English philosopher, friend of Aldous Huxley, and author of many books on the history of religion and mythology, visited the Harvard project early on and was very positive about the potential of psychedelics. He gave fascinating discourses on the role of psychedelic drugs in mystery cults in ancient times. He advised us not to publicize our findings, to stay underground, following the example of historical esoteric groups and secret societies. Needless to say, his advice was ignored; nothing could have been further from Tim Leary’s whole nature. Both the Concord prison study and the Good Friday mysticism study attracted a huge amount of attention, both from the academic communities and from the general public. Psychedelic drugs were fast becoming sensationalized in the media.
During the years to come I often wondered what would have happened had we followed Gerald Heard’s advice, thus letting psychedelic drugs become the exclusive province of a small group of visionary researchers and explorers. It did not seem to be the script we were called upon to follow. The experiences were too positive to not want to share them with everybody. It would appear that the time had come when this kind of experience should be made available to large numbers of searchers, so that “the doors of perception” could be opened, so that expanded consciousness was no longer something attainable only by rare individuals, but that it was here and now. The experience was a genuine view of what was possible. Those who felt the call to search could do so with a vivid knowledge of the goal.
The psilocybin project experienced increasing resistance from the Harvard University community. We were criticized that our research was loose and our approach uncontrolled and irresponsible. Let it be said here that these criticisms were prejudicial and not factual. To the contrary, as far as research is concerned, the project carried out and published several extensive
statistical and questionnaire studies on the drug experience. No one was ever given a drug without their knowledge, or against their wishes, or without full and complete preparation before and support during the experience. Tranquilizer antidotes were always available but no one ever requested their use. The existence and reports of the psilocybin research project naturally stimulated a lot of interest among Harvard students and thus led indirectly to a good deal of drug self-experimentation. Supplies of mescaline, peyote, and other substances were at that time easily obtained by anyone with a little ingenuity. At that time, there were no state or federal laws governing their use. It must also be said that although Leary and Alpert flooded the academic community with research papers, memoranda, and descriptions, some of the tone of their written and verbal pronouncements had a quality of messianic overenthusiasm that turned a lot of people off.
The Harvard academic establishment put more and more restrictions on the conduct of the research, largely because of the mounting sensationalism of media accounts. The legitimate source of psilocybin for the research project dried up. Graduate students working on the project, like myself, were told that they would not be permitted to do their doctoral dissertation on research administering psilocybin. (Walter Pahnke’s project was the last and only exception, and he was already an M.D., getting a Ph.D. in Religion.) With pressures mounting, we began to think of ways to carry on the work completely out of the University context. After two years of working exclusively with psilocybin in moderate dosages, LSD made its appearance, brought to Leary by a mysterious and unconventional Englishman named Michael Hollingshead. The depth and power of those experiences seemed several orders greater than psilocybin. We had referred to psilocybin as a “love drug” because of the interpersonal closeness that often developed among participants in a group session. LSD was never called that; with LSD, experiences of “ego-death” and “disintegration” became much more common.
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