1950s

The 1950s were the decade in which LSD and related compounds became a problem psychiatry could not easily name, classify, or contain. Researchers first treated their effects as temporary imitations of psychosis, then explored therapeutic models that made room for intense, sometimes spiritual experience. The decade’s changing vocabulary reflected more than scientific discovery: it registered a struggle over whether these drugs belonged to medicine, psychotherapy, or a domain that unsettled the boundaries between science and mysticism.

A new drug, a search for meaning

LSD had entered psychiatric research around 1950, but the questions it raised had begun with Albert Hofmann’s first experience in 1943. Uncertain whether he had encountered madness or transcendence, Hofmann nevertheless recognized the compound’s possible importance for neurology and psychiatry. Sandoz, the company where he worked, made LSD available as Delysid and offered it free to researchers and therapists willing to report their clinical observations. That unusual policy, in place more or less from 1949 to 1966, helped generate a worldwide research effort. The effects remained difficult to interpret: during the 1950s, scientists debated what the experiences meant and how they might be applied, while the United States Central Intelligence Agency was conducting classified research and considering LSD as a possible truth serum, mind-control agent, or chemical weapon.

The first influential label was “psychotomimetic”: a drug that mimicked psychosis. Observers reported depersonalization, altered body image, weakened ego boundaries, synesthesia, emotional swings, distortions of time, delirium, hallucinations, and paranoid delusions. Psychiatric tests administered to volunteers could produce results resembling those of people diagnosed with psychosis, especially schizophrenia. From this perspective, LSD was a potential instrument for studying mental illness, not necessarily a treatment for it. Sandoz initially marketed Delysid in that spirit. Some clinicians also took the drug themselves, reasoning that firsthand experience might help them understand and empathize with their patients. Before Congress gave the Food and Drug Administration authority over investigational drugs in 1962, such self-experimentation was common and could be regarded as an ethical safeguard against treating patients as guinea pigs.

From psychosis mimicry to therapy

Humphry Osmond helped make the psychosis-mimicry model scientifically productive, even though its central chemical hypothesis proved incorrect. After World War II, he and John Smythies explored whether schizophrenia might arise from a disturbance in adrenaline metabolism; mescaline’s molecular resemblance to adrenaline appeared to offer a clue. Osmond’s work contributed to the rise of neurochemistry, and later LSD research strengthened interest in the possibility that neurotransmitters and dedicated receptors helped organize mental experience. The striking effects of very small quantities of LSD eventually formed part of the context for the discovery of serotonin and the development of SSRIs.

Osmond’s research encountered opposition at St. George’s Hospital in London. Saskatchewan offered a different setting: its government was funding public health care and sought to attract medical researchers with resources and unusual freedom. After answering an advertisement in the Lancet, Osmond moved with his family to Weyburn, where the Saskatchewan Mental Hospital became a major center of research into compounds still called psychotomimetics. Abram Hoffer, a Canadian psychiatrist and research director, shared Osmond’s early framework. Their work with LSD from Sandoz began in an institution made possible by a province’s ambition to become a center of medical research.

The interpretive vocabulary shifted as researchers tried to account for more than resemblance to illness. “Psychedelic” entered the exchange between Osmond and Aldous Huxley in 1956 and was introduced as a term in 1957. Osmond had met Huxley in 1953, after the writer asked to try mescaline. Osmond traveled to Los Angeles to administer it; Huxley’s experience informed his 1954 book The Doors of Perception. The new word meant “mind manifesting,” and appealed to Osmond because it did not define the experience in advance as either madness or ecstasy. Its promise of neutrality, however, would not survive unchanged as the drug acquired new cultural associations.

The therapeutic session and its disputed inheritance

By the mid-1950s, Osmond and Hoffer were developing a therapeutic approach distinct from both psychosis research and ordinary talk therapy. A typical psychedelic-therapy session involved one high dose, comfortable surroundings, a couch, music, eyeshades, and a therapist or two who intervened sparingly. The arrangement aimed to reduce distraction and allow an inward experience to unfold, with the hope of producing an epiphany or conversion-like change. Rather than extending treatment through weekly meetings, the model centered on a single, carefully prepared session.

Osmond and Hoffer acknowledged that important elements of this design came from Al Hubbard, an unconventional practitioner without formal scientific or therapeutic training. A room arranged to feel like a home rather than a hospital became known as a Hubbard Room. The comfortable setting and the guide’s restrained presence were not incidental furnishings: they belonged to a treatment method in which the experience depended on more than the drug alone. The approach thus placed special weight on what later researchers would call set and setting, and brought therapy close to forms of spiritual practice that some psychiatrists regarded with suspicion.

A boundary under pressure

The decade’s new therapeutic model sharpened disagreements about what counted as legitimate psychiatric science. Psychotomimetic research could fit within familiar accounts of mental illness; psycholytic treatment could be understood as an aid to psychoanalysis. Psychedelic therapy was harder to accommodate because it proposed a high-dose session aimed at conversion, with patient and therapist roles altered by the experience and its spiritual framing. By the early 1960s, critics objected to researchers taking the drugs themselves and accused them of being compromised by their own experiences. The double-blind, placebo-controlled trial was also becoming the profession’s standard, although the conspicuous effects of psychedelics made blinding difficult and the influence of surroundings and expectation hard to separate from pharmacology.

In 1955, Hubbard established the Commission for the Study of Creative Imagination, recruiting Osmond, Hoffer, Huxley, Sidney Cohen, and others. Its name expressed an ambition to take psychedelic work beyond medicine’s focus on illness. Cohen resigned in 1957, and the commission’s existence marked a growing division between medical and spiritual approaches. Hubbard’s own stated distance from science as an end in itself made that division explicit. The shifting labels of the 1950s therefore tracked a shift in purpose as well as theory: from using drugs to imitate and investigate illness, toward asking whether they could change a person’s life or even reshape culture.

That unresolved boundary remains part of the decade’s legacy. Later researchers would again have to ask how to test a drug when its effects cannot easily be separated from expectation, the therapist, and the setting, or how medicine should assess a treatment whose apparent means is the experience it produces. At a 2017 conference, former mental-health leaders recognized psychedelic-assisted psychotherapy as a promising but unfamiliar model and warned that safety, rigor, and public trust were vulnerable to careless practice. The questions first made urgent in the 1950s had not disappeared; they had become the terms on which psychedelic research would seek renewed legitimacy.