Psychosis

Psychosis was both an observed resemblance and a contested explanation in the early study of LSD and psilocybin. Researchers initially understood these drugs through the Psychotomimetic paradigm: a temporary drug state that appeared to imitate mental illness. That interpretation made psychedelics seem useful for investigating psychosis, but volunteers’ reports of insight, unity, and lasting spiritual significance challenged the idea that resemblance to illness was the same as illness itself.

The Psychotomimetic Interpretation

Beginning around 1950, researchers called LSD psychotomimetic, meaning that it mimicked psychoses. From the outside, the case seemed plausible: volunteers could experience depersonalization, weakened ego boundaries, distorted body image, synesthesia, emotional lability, laughter or weeping, altered time perception, delirium, hallucinations, and paranoid delusions. One account described a tantalizing sense of portentousness. Standardized psychiatric tests, including Rorschach inkblots and the Minnesota Multiphasic Personality Inventory, produced results resembling those of people diagnosed with psychosis, especially schizophrenia. By these measures, the volunteers appeared to be losing their minds.

The resemblance also suggested a practical research use. Sandoz marketed Delysid partly as a way to investigate psychosis: if LSD could reproduce some symptoms associated with schizophrenia, perhaps it could help illuminate the disorder’s chemical basis. Clinicians also thought that taking the drug themselves might let them better understand their patients’ experiences. Before Congress gave the FDA authority to regulate new investigational drugs in 1962, self-experimentation was common and could be considered an ethical safeguard against treating patients as guinea pigs. Humphry Osmond described LSD’s promise as allowing a therapist to enter the illness and experience it from the patient’s point of view.

A Model Tested by Treatment

The psychosis model also shaped treatment experiments. Humphry Osmond and Abram Hoffer used a single high-dose LSD session in an attempt to induce an episode resembling delirium tremens, hoping the shock might help people with alcoholism become sober. Over the next decade, they tested the approach on more than seven hundred alcoholics and reported that roughly half remained sober for at least several months. The apparent success suggested a new therapeutic possibility, but it also made the volunteers’ subjective accounts central: the treatment’s significance might lie in the experience itself, not simply in the chemical or its resemblance to madness.

Those accounts strained the model. Some volunteers reported hallucinations, paranoia, or anxiety, yet many described experiences that sounded less like delirium than like transcendence: feeling united with the world, seeing themselves objectively, heightened sensory awareness, philosophical or religious understanding, and greater sensitivity to others. For many patients at Weyburn hospital, the experience seemed closer to a spiritual epiphany than a temporary psychosis. Osmond and Hoffer began to question whether the effects they had treated as madness might instead include mystical union, visionary experience, or ecstasy. The issue was not that difficult or harrowing reactions never occurred; it was that psychosis could not account for the range and meaning of what volunteers described.

Setting, Diagnosis, and Disagreement

The researchers also learned that the circumstances of a session could influence what followed. An engaged, empathetic therapist, preferably one who had personally experienced LSD, seemed to help prevent a bad session. Osmond and Hoffer suspected that some psychotic reactions might be shaped by the clinical environment itself: the metaphorical white room and the white-coated clinician. Although they did not yet use the later terms set and setting, their observations complicated any account that treated the drug alone as the cause of a uniform, psychotic state.

The dispute persisted in later research. At breakfast on the sunporch of his suburban Baltimore home, Roland Griffiths described a prominent colleague at Johns Hopkins University, Paul McHugh, who dismissed psychedelic experiences as toxic delirium. McHugh compared them to the colorful, hallucinatory, disorienting states that can occur when toxic products accumulate in the bodies of patients with advanced liver, kidney, or lung disease. Griffiths acknowledged that a temporary psychosis was possible and planned to test volunteers for delirium in an upcoming experiment, but doubted that the diagnosis captured their reports. People suffering from delirium, he argued, generally found it deeply unpleasant; his volunteers could later remember the experience as one of the most meaningful of their lives.

Beyond Symptom Resemblance

The book places this disagreement alongside William James’s caution about mystical states. James held that such experiences could be authoritative for the people who underwent them without obligating everyone else to accept their revelations uncritically. Yet their existence challenged the assumption that ordinary waking consciousness was the only valid judge of reality. He considered the possibility that apparently opposed aspects of experience might be reconciled in a larger unity, rather than dismissed as mere delusion.

The changing status of Psychosis therefore reflects a methodological as well as a diagnostic problem. Observable symptoms and psychiatric tests made the early comparison with schizophrenia intelligible, and the comparison generated hypotheses about the biology of mental illness. But volunteers’ contrasting reports, the therapeutic outcomes, and the influence of the session environment exposed the limits of treating surface resemblance as a complete explanation. The psychotomimetic model did not disappear because distressing reactions were unreal; it faltered because those reactions did not describe every experience, or settle what the experience meant. The unresolved distinction between illness-like symptoms and personally meaningful altered consciousness became one reason researchers sought new ways to understand the drugs and their effects.