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The visions, ecstatic states, and flights of imagination made possible by psychedelic drugs gave these substances an important role in many ancient cultures. Hundreds ofyears of anthropological research have demonstrated that these societies used psychedelics to maintain social solidarity, aid the healing arts, and inspire artistic and spiritual creativity.

New World aboriginal people used, and continue to use, a wide range of mind-altering plants and mushrooms. Most of what we know about psychedelics comes from investigating chemicals first found in Western Hemisphere materials: DMT, psilocybin, mescaline, and several LSD-like compounds.

The depth and breadth of psychedelic plant use by New World residents surprised and alarmed European settlers. Their reaction may have been due to the relative lack of psychedelic plants and mushrooms in Europe. Just as important was the association of mind-altering substances with witchcraft. The Church effectively suppressed information about the use of those materials in both the Old and New Worlds and persecuted bearers and practitioners of that knowledge. It is only in the last fifty years that we have realized that Mexican Indian use of magic mushrooms did not entirely die out in the sixteenth century.

In Europe, there was little interest in, or access to, psychedelic plants or drugs until the end of the late 1800s. Some authors described their own "psychedelic" reactions to opium or hashish, but the amount required for psychedelic effects was difficult to consume, excessive, or dangerous. This situation began to change with the discovery of mescaline mpeyote, a New World cactus.

German chemists isolated mescaline from peyote in the 1890s. The more literary among those exploring its effects hailed its ability to open the gates of an "artificial paradise." However, medical and psychiatric interest in mescaline was surprisingly restrained, and researchers published only a limited number of papers by the end of the 1930s. The unpleasant nausea and vomiting that often occur with mescaline may have had something to do with the lack of interest in it.

Another reason for the minimal enthusiasm about mescaline may have been that there was no scientific or medical context in which to understand its effects. Freudian psychoanalysis was that era's predominant force in psychiatry. While Freud himself was strongly attracted to mind-altering drugs such as cocaine and tobacco, his students were less so. In addition, Freud distrusted religion and believed spiritual or religious experience was a defense against childish fears and wishes. This attitude probably did little to encourage investigation of mescaline, with its trappings of Native American spirituality. Then LSD made its revolutionary appearance.

In 1938 the Swiss chemist Albert Hofmann was working with ergot, a rye fungus, in the natural products division of Sandoz Laboratories, even then a maj or pharmaceutical company. He hoped to find a drug that might help stop uterine bleeding after childbirth. One of these ergot-based compounds was LSD-25, or lysergic acid diethylamide. It had little effect on the uterus of laboratory animals, and Hofmann shelved it. Five years later, "a curious presentiment" called Hofmann back to examine LSD, and he accidentally discovered its powerful psychedelic properties.

The remarkable thing about LSD was that it brought on psychedelic effects at doses of millionths of a gram, which meant that it had more than one thousand times the strength of mescaline. In fact, Hofmann nearly overdosed himself with what he thought was too small a quantity to possibly be mind-altering: a quarter milligram. Hoffman and his Swiss colleagues were quick to publish their findings in the early 1940s. Because of the highly altered state of mind LSD produced, and the traditional psychiatric context in which researchers explored it, scientists decided to emphasize its "psychosis-mimicking" properties.1

The years after World War II were exciting ones for psychiatry. In addition to LSD, scientists also discovered the "antipsychotic" properties of chlor-promazine, or Thorazine. Thorazine made it possible for severely mentally 11 patients to improve enough that they could leave asylums in unprecedented numbers. This and other antipsychotic medications finally allowed doctors to make progress in treating some of our most disabling illnesses.

The contemporary field of "biological psychiatry" was born in those years. This discipline, which studies the relationship between the human

mind and its brain chemistry, was the child of these two strange bedfellows: LSD and Thorazine. And serotonin was the matchmaker.

In 1948 researchers discovered that serotonin carried in the bloodstream was responsible for contracting the muscles lining veins and arteries. This was vitally important in understanding how to control the bleeding process. The name for serotonin came from the Latin sew, "blood," and tonin, "tightening."

A few years later, in the mid-1950s, investigators discovered serotonin in the brain of laboratory animals. Subsequent experiments demonstrated its precise localization and its effects on electrical and chemical functions of individual nerve cells. Drugs or surgery that modified serotonin-containing areas of an animal's brain profoundly altered sexual and aggressive behavior as well as sleep, wakefulness, and a diverse array of basic biological functions. The presence and function of serotonin in the brain and in animal behavior clinched its role as the first known neurotransmitter.2

At the same time, scientists showed that LSD and serotonin molecules looked very much like each other. They then demonstrated that LSD and serotonin competed for many of the same brain sites. In some experimental situations, LSD blocked the effects of serotonin; in others, the psychedelic drug mimicked serotonin's effects.

These findings established LSD as the most powerful tool available for learning about brain-mind relationships. If LSD's extraordinary sensory and emotional properties resulted from changing the function ofbrain serotonin in specific and understandable ways, it might be possible to "chemically dissect" particular mental functions into their basic physiological components. Other mind-altering drugs with comparably well-characterized effects on different neurotransmitters could lead to a decoding of the varieties of conscious experience into their underlying chemical mechanisms.

Dozens of investigators around the world administered a dizzying array of psychedelic drugs to thousands of healthy volunteers and psychiatric patients. For more than two decades, generous government and private funding supported this effort. Researchers published hundreds of papers and dozens of books. Many international conferences, meetings, and symposia discussed the latest findings in human psychedelic drug research.3

Sandoz Laboratories distributed LSD to researchers so they might induce a brief psychotic state in normal volunteers. Scientists hoped such experiments might shed light on naturally occurring psychotic disorders like schizophrenia.

Sandoz also recommended giving LSD to psychiatric interns to help them establish a sense of empathy for their psychotic patients. These young doctors were amazed by this temporary encounter with insanity. The raw encounter with their own previously unconscious memories and feelings led these psychiatrists to believe that these mind-loosening properties might enhance psychotherapy.

Numerous research publications suggested that the normal mechanisms of talk therapy were much more effective with the addition of a psychedelic drug. Dozens of scientific articles described remarkable success in helping previously untreatable patients suffering from obsessions and compulsions, post-traumatic stress, eating disorders, anxiety, depression, alcoholism, and heroin dependence.

The rapid breakthroughs described by researchers using "psychedelic psychotherapy" spurred other investigators to study these drugs' beneficial effects in despairing and pain-ridden terminally ill patients. While there was little effect on the underlying medical conditions, psychedelic psychotherapy in these patients had striking psychological effects. Depression lifted, requirements for pain medication fell dramatically, and patients acceptance of their disease and its prognosis improved markedly. In addition, patients and their families seemed able to address deep-seated and emotionally charged issues in ways never before possible. The rapid accleration of psychological growth resulting from this new treatment appeared quite promising in these cases where time was of the essence. Some therapists believed that a transformative, mystical, or spiritual experience was responsible for many of these "miraculous" responses to psychedelic psychotherapy.4

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In addition, it soon became apparent that the experiences described by volunteers under deep psychedelic influences were strikingly similar to those of practitioners of traditional Eastern meditation. The overlap between consciousness alteration induced by psychedelic drugs and that induced by meditation attracted the attention of writers outside of academics, including the English novelist and religious philosopher Aldous Huxley. Huxley underwent his own remarkably positive mescaline and LSD experiences under the watchful eye of the Canadian psychiatrist Humphrey Osmond, who visited him in Los Angeles in the 1950s. Huxley soon wrote about his drug sessions and the musings they inspired in him. His writings on the nature and value of the psychedelic experience were compelling and eloquent, inspiring many individuals' attempts to attain, and researchers to elicit, spiritual enlightenment through psychedelic drugs. Despite that fact that his ideas stimulated a massive movement toward popular experimentation with the psychedelics, Huxley was a staunch advocate of the theory that only an elite group of intellectuals and artists should have access to them. He did not believe that the common man or woman was capable of using psychedelics in the safest and most productive ways possible.5

However, terminal illness studies and discussions of similarities between psychedelic drug effects and mystical experiences brought religion and science together in an uneasy mix. The research was moving further away from Sandoz's original agenda.

Complicating things further was LSD's escape from the laboratory in the 1960s. Reports of emergency room visits, suicides, murders, birth defects, and broken chromosomes filled the media. The highly publicized abandonment of scientific research principles by Timothy Leary, Ph.D., and his research team at Harvard University ultimately resulted in their dismissals. These events reinforced the growing suspicion that even the scientists had lost control of these powerful psychoactive drugs.6

The media exaggerated and emphasized psychedelic drugs' negative physical and psychological effects. Some of these reports resulted from poor research; others were simply fabricated. Subsequent publications cleared psychedelics from serious toxicity, including chromosome dam-


age. However, these follow-up studies generated much less fanfare than did the original damaging reports.

Papers in the psychiatric literature describing "bad trips," or adverse psychological reactions to psychedelics, also multiplied, but are similarly limited. In order to address these concerns in my own study, I read every paper describing such negative effects and published the results. It was clear that rates of psychiatric complications were extraordinarily low in controlled research settings, for both normal volunteers and psychiatric patients. However, when psychiatrically ill or unstable individuals took impure or unknown psychedelics, combined with alcohol and other drugs, in an uncontrolled setting with inadequate supervision, problems occurred.7

In response to the public's anxiety about uncontrolled LSD use, and over the objections of nearly every investigator in the field, the United States Congress passed a law in 1970 making LSD and other psychedelics illegal. The government told scientists to return their drugs, paperwork requirements for obtaining and maintaining new supplies of psychedelics for research became a time-consuming and confusing burden, and there was little hope for new projects. Money for studies dried up and researchers abandoned their experiments. With the new drug laws in place, interest in human psychedelic research died off almost as rapidly as it had begun. It was as if the psychedelic drugs became "un-discovered."

Considering the intense pace of human research with psychedelics just thirty years ago, it is amazing how little today's medical and psychiatric training programs teach about them. Psychedelics were the growth area in psychiatry for over twenty years. Now young physicians and psychiatrists know nearly nothing about them.

By the time I was a medical student in the mid-1970s, less than ten years after the drug laws changed, psychedelics were the topic ofjust two lectures in my four years of study. Even this may have been more information than students received at most other medical schools, because there was a research group performing animal studies at the Albert Einstein College of Medicine in New York City, where I trained. In the mid-1990s,


I taught a psychedelic drug research seminar to senior psychiatric residents at the University of New Mexico—probably the only one of its kind in the country in decades.

The lack of academic attention to psychedelics may have been partly due to the absence of any ongoing human research. However, it is common for physicians-in-training to learn about previously popular theories and techniques, even if they no longer are in favor. The psychedelic drugs, however, seemed to have dropped out of all psychiatric dialogue.

Most new theories, techniques, and drugs in the clinical psychiatric field follow a predictable course of evolution as they are introduced, tested, and refined for further application. Therefore, it was not at all surprising that conflicting results began to emerge as more data accumulated during the first wave of human psychedelic research. Enthusiasm predictably slowed for claims that psychedelics could produce a "model psychosis" or "cures" in intractable psychotherapy cases. The natural process within psychiatric research is for scientists to refine research questions, methods, and applications. This never happened with the psychedelic drugs. Instead, their study went through a highly unnatural evolution. They began as "wonder drugs," turned into "horror drugs," then became nothing.

I believe that medical students and psychiatric trainees learn so little about psychedelic drugs not because research did end, but because of how it ended. This process deeply demoralized academic psychiatry, which then turned its back on psychedelic drugs.

Psychedelic research was a bruising and humiliating chapter in the lives of many of its most prominent scientists. These were the best and the brightest psychiatrists of their generation. Many of today's most respected North American and European psychiatric researchers, in both academics and industry, now chairmen of major university departments and presidents of national psychiatric organizations, began their professional lives investigating psychedelic drugs. The most powerful members of their profession discovered that science, data, and reason were incapable of defending their research against the enactment of repressive laws fueled by opinion, emotion, and the media.

Once these laws passed, government regulators and funding agencies quickly withdrew permits, drugs, and money. The same psychedelic drugs that researchers thought were unique keys to mental illness, and that had launched dozens of careers, became feared and hated.

Another problem was that psychedelics were becoming an embarrassing source of contention even within psychiatry itself. Biology-based psychiatrists had little patience with colleagues who "found religion" and touted the spiritual effects of these drugs. These latter researchers viewed their brain-only associates as narrow-minded and repressed. Psychiatry has never been especially comfortable with spiritual issues, and in fact, an entirely new division appeared in the field to contend with results from psychedelic research: the "transpersonal" area of theory and practice. Thus, at least some psychedelic researchers may have been quietly relieved that they no longer had to face many of the complex, contradictory, and confusing effects these drugs produced in their patients, themselves, and their colleagues.

Why would anyone want to lecture on this embarrassing chapter in academic psychiatry to an auditorium packed with two hundred sharp-witted medical students? This early group of psychedelic researchers was for the most part professional scientists, not zealots. They knew enough not to publicly criticize the behavior of their colleagues and benefactors. Better to live and learn.8

Now that we have reviewed some important background of the psychedelics, let's look at what they do.

Psychedelics exert their effects by a complex blending of three factors: set, setting, and drug.

Set is our own makeup, both long term and immediate. It is our past, our present, and our potential future; our preferences, ideas, habits, and feelings. Set also includes our body and brain.

The psychedelic experience also hinges on setting: who or what is or isn t in our immediate surroundings; the environment we're in, whether natural or urban, indoor or outdoor; the quality of the air and ambient sound around us; and so on. Setting also partakes ofthe sefofwho is with us while we take the drug, whether they be a friend or a stranger, relaxed or tense, a supportive guide or a probing scientist.

Then, there is the drug.

First, what do we call it? Even among researchers there is little agreement over this crucial point. Some don't even use the word drug, preferring instead molecule, compound, agent, substance, medicine, or sacrament.

Even if we agree to call it a drug, look at how many different names it has: hallucinogen (producing hallucinations), entheogen (generating the divine), mysticomimetic (mimicking mystical states), oneirogen (producing dreams), phanerothyme (producing visible feelings), phantasticant (stimulating fantasy), psychodysleptic (mind-disturbing), psychotomimetic andpsychotogen (mimicking or producing psychosis, respectively), and psychotoxin and schizotoxin (a poison causing psychosis or schizophrenia, respectively).

This focus on name is not trivial. If everyone agreed about what a psychedelic is or does, there certainly would not be so many words for the same drug. The multitude of labels reflects the deep-seated and ongoing debate about psychedelic drugs and their effects.

Scientists rarely acknowledge the importance of the name they give to psychedelics, even though they know how powerfully expectations modify drug effects. All undergraduate psychology students learn this in their introductory psychology courses when they review landmark studies published in the 1960s. These experiments injected volunteers with adrenaline, the "fight-or-flight" hormone, under different sets of expectations. Adrenaline caused a calm and relaxed state in volunteers told they were receiving a sedative. If told that the experimental drug was stimulating, volunteers felt the more typical anxiety and energy.9

Thus, what we call a drug we take, or give, influences our expectations of what that drug will do. It also modifies the effects themselves, and how we interpret and deal with them. No other drug's name feeds back so powerfully upon the responses they elicit as do the psychedelics, because they greatly magnify our suggestibility.

In addition to what we call psychedelics, the terms we apply to the people involved in their use also impact set and setting, and therefore drug response. As one who takes the drug, are we research subjects or volunteers? Clients or celebrants? As the one giving them, are we guides, sitters, or research investigators? Shamans or scientists?

Try this mental exercise: Consider how you might look forward to your day as a "research subject" under the influence of a "psychotomimetic agent." Then reconsider: How would you feel about your role as a "celebrant" in a "ceremony" involving an "entheogenic sacrament"? How would these different contexts affect your interpretation of the hallucinations and intense mood swings brought on by the drug? Would you be "going crazy" or having an "enlightenment experience"?

If you were administering psychedelics, what types of behavior would you anticipate in your research subject, and what sorts would you ignore? Much would depend upon whether you were giving a "schizotoxin" or a "phantasticant." You might encourage an "out-of-body experience" in a "shamanic" context, but abort the same effects by giving an antipsychotic antidote in a "psychotomimetic" one.10

Hallucinogen is the most common medical term for psychedelic drugs, and it emphasizes the perceptual, mostly visual effects of these drugs. However, while perceptual effects of psychedelics are usual, they are not the only effects, nor are they necessarily the most valued. The visions actually may be distractions from the more sought-after properties of the experience, such as intense euphoria, profound intellectual or spiritual insights, and the dissolving of the body's physical boundaries.

I prefer the term psychedelic, or mind-manifesting, over hallucinogen. Psychedelics show you what's in and on your mind, those subconscious thoughts and feelings that are are hidden, covered up, forgotten, out of sight, maybe even completely unexpected, but nevertheless imminently present. Depending upon set and setting, the same drug, at the same dose, can cause vastly different responses in the same person. One day, very little happens; another day, you soar, full of ecstatic and insightful discoveries; the next, you struggle through a terrifying nightmare. The generic nature of psychedelic, a term wide open to interpretation, suits these effects.

Psychedelic has taken on its own cultural and linguistic life. It now can refer to a particular style of art, clothing, or even an especially intense set of circumstances. When it comes to rational discourse about drugs, psychedelic also stirs up powerful 1960s-based emotions and con-Uicts over unrelated political and sociological issues. Many of us now

think "counterculture," "rebellious," "liberal," or "left-wing" when we see the term "psychedelic." I will take my chances, however, and use it throughout this book. I think it is the best term we have. I hope not to offend anyone who finds the word objectionable.

No matter what we call them, most of us agree that the psychedelic drugs are physical, chemical things. It is at this most basic level that we can begin to understand what they are and what they do.

The diagrams accompanying the following descriptions show the chemical structure of various psychedelic compounds. The balls represent atoms, the most common of which is carbon, which is not labeled. "N" signifies nitrogen; "P," phosphorous; and "0," oxygen. Numerous hydrogen atoms are attached to other atoms in the molecules; however, there are so many that they would unnecessarily clutter up the diagram, so I have not included them here.

There are two main chemical families of psychedelic drugs: the phenethylamines and the tryptamines.11

The phenethylamines build upon the "parent compound" phenethylamine.

Phenethylamine Pill

The best-known phenethylamine is mescaline, which is derived from the peyote cactus of the American Southwest.

Another famous phenethylamine is MDMA, or "Ecstasy."


The other main chemical family of psychedelic drugs is the tryptamines. These all possess a nucleus, or basic building block, of tryptamine. Tryptamine is a derivative of tryptophan, an amino acid present in our diet.

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