So what was learned during that fertile and freewheeling period of investigation? A straightforward question, and yet the answer is complicated by the very nature of these drugs, which is anything but straightforward. As the literary theorists would say, the psychedelic experience is highly “constructed.” If you are told you will have a spiritual experience, chances are pretty good that you will, and, likewise, if you are told the drug may drive you temporarily insane, or acquaint you with the collective unconscious, or help you access “cosmic consciousness,” or revisit the trauma of your birth, you stand a good chance of having exactly that kind of experience.
Psychologists call these self-fulfilling prophecies “expectancy effects,” and they turn out to be especially powerful in the case of psychedelics. So, for example, if you have ever read Aldous Huxley’s Doors of Perception, which was published in 1954, your own psychedelic experience has probably been influenced by the author’s mysticism and, specifically, the mysticism of the East to which Huxley was inclined. Indeed, even if you have never read Huxley, his construction of the experience has probably influenced your own, for that Eastern flavoring—think of the Beatles song “Tomorrow Never Knows”—would come to characterize the LSD experience from 1954 on. (Leary would pick up this psychedelic orientalism from Huxley and then greatly amplify it when he and his Harvard colleagues wrote a bestselling manual for psychedelic experience based on the Tibetan Book of the Dead.) Further complicating the story and adding another feedback loop, Huxley was inspired to try psychedelics and write about the experience by a scientist who gave him mescaline in the explicit hope that a great writer’s descriptions and metaphors would help him and his colleagues make sense of an experience they were struggling to interpret. So did Aldous Huxley “make sense” of the modern psychedelic experience, or did he in some sense invent it?
This hall of epistemological mirrors was just one of the many challenges facing the researchers who wanted to bring LSD into the field of psychiatry and psychotherapy: psychedelic therapy could look more like shamanism or faith healing than medicine. Another challenge was the irrational exuberance that seemed to infect any researchers who got involved with LSD, an enthusiasm that might have improved the results of their experiments at the same time it fueled the skepticism of colleagues who remained psychedelic virgins. Yet a third challenge was how to fit psychedelics into the existing structures of science and psychiatry, if indeed that was possible. How do you do a controlled experiment with a psychedelic? How do you effectively blind your patients and clinicians or control for the powerful expectancy effect? When “set” and “setting” play such a big role in the patient’s experience, how can you hope to isolate a single variable or design a therapeutic application?
Part I: The Promise
The drugs weren’t called “psychedelics” at the beginning; that term wasn’t introduced until 1957. In the same way that Sandoz couldn’t figure out what it had on its hands with LSD, the researchers experimenting with the drug couldn’t figure out what to call it. Over the course of the 1950s, this class of drugs underwent a succession of name changes as our understanding of the chemicals and their action evolved, each new name reflecting the shifting interpretation—or was it a construction?—of what these strange and powerful molecules meant and did.
The first name was perhaps the most awkward: beginning around 1950, shortly after LSD was made available to researchers, the compound was known as a psychotomimetic, which is to say, a mind drug that mimicked psychoses. This was the most obvious and parsimonious interpretation of a psychedelic’s effects. Viewed from the outside, people given doses of LSD and, later, psilocybin exhibited many of the signs of a temporary psychosis. Early researchers reported a range of disturbing symptoms in their LSD volunteers, including depersonalization, loss of ego boundaries, distorted body image, synesthesia (seeing sounds or hearing sights), emotional lability, giggling and weeping, distortion of the sense of time, delirium, hallucinations, paranoid delusions, and, in the words of one writer, “a tantalizing sense of portentousness.” When researchers administered standardized psychiatric tests to volunteers on LSD—such as the Rorschach ink blots or the Minnesota Multiphasic Personality Inventory test—the results mirrored those of psychotics and, specifically, schizophrenics. Volunteers on LSD appeared to be losing their minds.
This suggested to some researchers that LSD held promise as a tool for understanding psychosis, which is precisely how Sandoz initially marketed Delysid. Although the drug might not cure anything, the resemblance of its effects to the symptoms of schizophrenia suggested that the mental disorder might have a chemical basis that LSD could somehow illuminate. For clinicians, the drug promised to help them better understand and empathize with their schizophrenic patients. That of course meant taking the drug themselves, which seems odd, even scandalous, to us today. But in the years before 1962, when Congress passed a law giving the FDA authority to regulate new “investigational” drugs, this was in fact common practice. Indeed, it was considered the ethical thing to do, for to not take the drug yourself was tantamount to treating your patients as guinea pigs. Humphry Osmond wrote that the extraordinary promise of LSD was to allow the therapist who took it to “enter the illness and see with a madman’s eyes, hear with his ears, and feel with his skin.”
Born in Surrey, England, in 1917, Osmond is a little-known but pivotal figure in the history of psychedelic research,* probably contributing more to our understanding of these compounds and their therapeutic potential than any other single researcher. In the years following World War II, Osmond, a tall reed of a man with raucous teeth, was practicing psychiatry at St. George’s Hospital in London when a colleague named John Smythies introduced him to an obscure body of medical literature about mescaline. After learning that mescaline induced hallucinations much like those reported by schizophrenics, the two researchers began to explore the idea that the disease was caused by a chemical imbalance in the brain. At a time when the role of brain chemistry in mental illness had not yet been established, this was a radical hypothesis. The two psychiatrists had observed that the molecular structure of mescaline closely resembled that of adrenaline. Could schizophrenia result from some kind of dysfunction in the metabolism of adrenaline, transforming it into a compound that produced the schizophrenic rupture with reality?
No, as it would turn out. But it was a productive hypothesis even so, and Osmond’s research into the biochemical basis of mental illness contributed to the rise of neurochemistry in the 1950s. LSD research would eventually give an important boost to the nascent field. The fact that such a vanishingly small number of LSD molecules could exert such a profound effect on the mind was an important clue that a system of neurotransmitters with dedicated receptors might play a role in organizing our mental experience. This insight eventually led to the discovery of serotonin and the class of antidepressants known as SSRIs.
But the powers that be at St. George’s Hospital were unsupportive of Osmond’s research on mescaline. In frustration, the young doctor went looking for a more hospitable institution in which to conduct it. This he found in the western Canadian province of Saskatchewan, of all places. Beginning in the mid-1940s, the province’s leftist government had instituted several radical reforms in public policy, including the nation’s first system of publicly funded health care. (It became the model for the system Canada would adopt in 1966.) Hoping to make the province a center of cutting-edge medical research, the government offered generous funding and a rare degree of freedom to lure researchers to the frozen wastes of the Canadian prairies. After replying to an ad in the Lancet, Osmond received an invitation from the provincial government to move his family and his novel research project to the remote agrarian community of Weyburn, Saskatchewan, forty-five miles north of the North Dakota border. The Saskatchewan Mental Hospital in Weyburn would soon become the world’s most important hub of research into psychedelics—or rather, into the class of compounds still known as psyc
hotomimetics.
That paradigm still ruled the thinking of Osmond and his new, like-minded colleague and research director, a Canadian psychiatrist named Abram Hoffer, as they began conducting experiments using a supply of LSD-25 obtained from Sandoz. The psychotomimetic model was introduced to the general public in 1953, when Maclean’s, the popular Canadian magazine, published a harrowing account of a journalist’s experience on LSD titled “My 12 Hours as a Madman.”
Sidney Katz had become the first “civilian” to participate in one of Osmond and Hoffer’s LSD experiments at Weyburn hospital. Katz had been led to expect madness, and madness he duly experienced: “I saw faces of familiar friends turn into fleshless skulls and the heads of menacing witches, pigs and weasels. The gaily patterned carpet at my feet was transformed into a fabulous heaving mass of living matter, part vegetable, part animal.” Katz’s article, which was illustrated with an artist’s rendering of chairs flying through a collapsing room, reads like the work of a fervent anti-LSD propagandist circa 1965: “I was repeatedly held in the grip of a terrifying hallucination in which I could feel and see my body convulse and shrink until all that remained was a hard sickly stone.” Yet, curiously, his twelve hours of insanity “were not all filled with horror,” he reported. “At times I beheld visions of dazzling beauty—visions so rapturous, so unearthly, that no artist will ever paint them.”
During this period, Osmond and Hoffer administered Sandoz LSD to dozens of people, including colleagues, friends, family members, volunteers, and, of course, themselves. Their focus on LSD as a window into the biochemistry of mental illness gradually gave way to a deepening curiosity about the power of the experience itself and whether the perceptual disturbances produced by the drug might themselves confer some therapeutic benefit. During a late night brainstorming session in an Ottawa hotel room in 1953, Osmond and Hoffer noted that the LSD experience appeared to share many features with the descriptions of delirium tremens reported by alcoholics—the hellish, days-long bout of madness alcoholics often suffer while in the throes of withdrawal. Many recovering alcoholics look back on the hallucinatory horrors of the DTs as a conversion experience and the basis of the spiritual awakening that allows them to remain sober.
The idea that an LSD experience could mimic the DTs “seemed so bizarre that we laughed uproariously,” Hoffer recalled years later. “But when our laughter subsided, the question seemed less comical and we formed our hypothesis . . . : would a controlled LSD-produced delirium help alcoholics stay sober?”
Here was an arresting application of the psychotomimetic paradigm: use a single high-dose LSD session to induce an episode of madness in an alcoholic that would simulate delirium tremens, shocking the patient into sobriety. Over the next decade, Osmond and Hoffer tested this hypothesis on more than seven hundred alcoholics, and in roughly half the cases, they reported, the treatment worked: the volunteers got sober and remained so for at least several months. Not only was the new approach more effective than other therapies, but it suggested a whole new way to think about psychopharmacology. “From the first,” Hoffer wrote, “we considered not the chemical, but the experience as a key factor in therapy.” This novel idea would become a central tenet of psychedelic therapy.
The emphasis on what subjects felt represented a major break with the prevailing ideas of behaviorism in psychology, in which only observable and measurable outcomes counted and subjective experience was deemed irrelevant. The analysis of these subjective experiences, sometimes called phenomenology, had of course been the basis of Freudian psychoanalysis, which behaviorism had rejected as insufficiently rigorous or scientific. There was no point in trying to get inside the mind; it was, in B. F. Skinner’s famous phrase, “a black box.” Instead, you measured what you could measure, which was outward behavior. The work with psychedelics would eventually spark a revival of interest in the subjective dimensions of the mind—in consciousness. How ironic that it took, of all things, a chemical—LSD-25—to bring interiority back into psychology.
And yet, successful as the new therapy seemed to be, there was a nagging little problem with the theoretical model on which it was based. When the therapists began to analyze the reports of volunteers, their subjective experiences while on LSD bore little if any resemblance to the horrors of the DTs, or to madness of any kind. To the contrary, their experiences were, for the most part, incredibly—and bafflingly—positive. When Osmond and Hoffer began to catalog their volunteers’ session reports, “psychotic changes”—hallucinations, paranoia, anxiety—sometimes occurred, but there were also descriptions of, say, “a transcendental feeling of being united with the world,” one of the most common feelings reported. Rather than madness, most volunteers described sensations such as a new ability “to see oneself objectively”; “enhancement in the sensory fields”; profound new understandings “in the field of philosophy or religion”; and “increased sensitivity to the feelings of others.”* In spite of the powerful expectancy effect, symptoms that looked nothing like those of insanity were busting through the researchers’ preconceptions.
For many of the alcoholics treated at Weyburn hospital, the core of the LSD experience seemed to involve something closer to transcendence, or spiritual epiphany, than temporary psychosis. Osmond and Hoffer began to entertain doubts about their delirium tremens model and, eventually, to wonder if perhaps the whole psychotomimetic paradigm—and name for these drugs—might need retooling. They received a strong push in that direction from Aldous Huxley after his mescaline experience, which he declared bore scant resemblance to psychosis. What a psychiatrist might diagnose as depersonalization, hallucinations, or mania might better be thought of as instances of mystical union, visionary experience, or ecstasy. Could it be that the doctors were mistaking transcendence for insanity?
At the same time, Osmond and Hoffer were learning from their volunteers that the environment in which the LSD session took place exerted a powerful effect on the kinds of experiences people had and that one of the best ways to avoid a bad session was the presence of an engaged and empathetic therapist, ideally someone who had had his or her own LSD experience. They came to suspect that the few psychotic reactions they did observe might actually be an artifact of the metaphorical white room and white-coated clinician. Though the terms “set” and “setting” would not be used in this context for several more years (and became closely identified with Timothy Leary’s work at Harvard a decade later), Osmond and Hoffer were already coming to appreciate the supreme importance of those factors in the success of their treatment.
But however it worked, it worked, or certainly seemed to: by the end of the decade, LSD was widely regarded in North America as a miracle cure for alcohol addiction. Based on this success, the Saskatchewan provincial government helped develop policies making LSD therapy a standard treatment option for alcoholics in the province. Yet not everyone in the Canadian medical establishment found the Saskatchewan results credible: they seemed too good to be true. In the early 1960s, the Addiction Research Foundation in Toronto, the leading institute of its kind in Canada, set out to replicate the Saskatchewan trials using better controls. Hoping to isolate the effects of the drug from all other variables, clinicians administered LSD to alcoholics in neutral rooms and under instructions not to engage with them during their trips, except to administer an extensive questionnaire. The volunteers were then put in constraints or blindfolded, or both. Not surprisingly, the results failed to match those obtained by Osmond and Hoffer. Worse still, more than a few of the volunteers endured terrifying experiences—bad trips, as they would come to be called. Critics of treating alcoholics with LSD concluded that the treatment didn’t work as well under rigorously controlled conditions, which was true enough, while supporters of the practice concluded that attention to set and setting was essential to the success of LSD therapy, which was also true.
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IN THE MID-1950S, Bill Wilson, the cofo
under of Alcoholics Anonymous, learned about Osmond and Hoffer’s work with alcoholics. The idea that a drug could occasion a life-changing spiritual experience was not exactly news to Bill W., as he was known in the fellowship. He credited his own sobriety to a mystical experience he had on belladonna, a plant-derived alkaloid with hallucinogenic properties that was administered to him at Towns Hospital in Manhattan in 1934. Few members of AA realize that the whole idea of a spiritual awakening leading one to surrender to a “higher power”—a cornerstone of Alcoholics Anonymous—can be traced to a psychedelic drug trip.
Twenty years later, Bill W. became curious to see if LSD, this new wonder drug, might prove useful in helping recovering alcoholics have such an awakening. Through Humphry Osmond he got in touch with Sidney Cohen, an internist at the Brentwood VA hospital (and, later, UCLA) who had been experimenting with Sandoz LSD since 1955. Beginning in 1956, Bill W. had several LSD sessions in Los Angeles with Sidney Cohen and Betty Eisner, a young psychologist who had recently completed her doctorate at UCLA. Along with the psychiatrist Oscar Janiger, Cohen and Eisner were by then leading figures in a new hub of LSD research loosely centered on UCLA. By the mid-1950s, there were perhaps a dozen such hubs in North America and Europe; most of them kept in close contact with one another, sharing techniques, discoveries, and, sometimes, drugs, in a spirit that was generally more cooperative than competitive.
Bill W.’s sessions with Cohen and Eisner convinced him that LSD could reliably occasion the kind of spiritual awakening he believed one needed in order to get sober; however, he did not believe the LSD experience was anything like the DTs, thus driving another nail in the coffin of that idea. Bill W. thought there might be a place for LSD therapy in AA, but his colleagues on the board of the fellowship strongly disagreed, believing that to condone the use of any mind-altering substance risked muddying the organization’s brand and message.