Many of us know only one side of the story of psychedelic therapy. In the 1950s and early 1960s, psychiatrists gave LSD and mescaline to patients struggling with depression, anxiety, and addiction. They hoped to create a powerful spiritual experience that would produce lasting change.
Among the celebrities who vouched for this new method of treatment were movie star Cary Grant, writer Anaïs Nin, and Bill W., founder of Alcoholics Anonymous.
But after LSD spread into the larger culture, the U.S. government imposed strict restrictions on it (Dyck, 2008). By 1966, it became very difficult for researchers to conduct experiments with LSD. Today’s psychedelic therapists see themselves as heirs to this earlier tradition.
But as I explore in my recent book, psychiatrists in the 1950s and ’60s also used LSD not to heal mental illness, but to induce it. They believed that if they had a drug that could reliably produce psychosis in healthy volunteers, they could finally uncover the biological basis of schizophrenia.
A Pill to Make Madness
In the 1950s, doctors noted the similarity between LSD trips and psychosis associated with schizophrenia. Both LSD users and patients with schizophrenia seemed to suffer a radical break with reality, replete with hallucinations and delusions.
That observation led some doctors to a far-reaching conclusion: What if LSD trips and schizophrenia share the same underlying mechanism? If so, they reasoned, understanding LSD’s effects might reveal the origin of schizophrenia.
By 1954, two research groups, on the basis of this notion, proposed a “serotonin hypothesis of schizophrenia.” Their experiments with LSD suggested that it reduced serotonin levels in the brain. They wondered whether schizophrenia, too, stemmed from a serotonin deficiency.
Doctors also used LSD and related psychedelic drugs to try to induce a schizophrenia-like state in healthy volunteers. For example, the psychiatrist Leo Hollister famously administered LSD to volunteers, including Ken Kesey, whose experience with the drug led him to write One Flew Over the Cuckoo’s Nest.
Some of this work likely overlapped with the CIA’s top-secret MK-Ultra program, which explored LSD as a potential truth serum. (Some researchers have claimed that Hollister received CIA funding for this program, though I have not been able to independently verify this.)
LSD and the Brain
One of the key players in this quest to explore the link between schizophrenia and LSD was Solomon Snyder, a neuroscientist and psychiatrist at Johns Hopkins University.
In the early 1960s, an LSD trip during his medical residency led him to think that LSD could mimic schizophrenia. He felt that time slowed down and that his very “self” had evaporated. He wondered if patients with schizophrenia had similar experiences.
The problem was that nobody knew exactly what LSD did to the brain. Snyder was unconvinced by the reigning theory that LSD worked by depleting brain serotonin. After all, he reasoned, there were drugs that deplete serotonin but had no psychedelic effect. (We now know that LSD and related drugs actually work by activating a subtype of the serotonin receptor.)
In the mid-1960s, Snyder worked hard to understand what LSD does to the brain. He injected monkeys with radioactive LSD and dissected their brains to better understand where it went. He built mathematical models to show how LSD’s molecular structure might affect brain cells.
He even gave a psychedelic drug called STP to his students at Hopkins to see whether it could induce psychosis (Snyder et al. 1967). Unfortunately for Snyder, the legal restrictions on LSD largely brought his work with the drug to a halt.
From LSD to Amphetamines
Eventually, Snyder turned his attention to the power of amphetamines to create madness.
By the late 1960s, the United States was in the midst of an amphetamine epidemic. People who took large quantities of amphetamines often developed psychosis. Some were even misdiagnosed with schizophrenia. Some doctors even gave amphetamines to volunteers in an attempt to induce psychosis.
By 1970, Snyder proved that amphetamines cause psychosis by flooding the brain with dopamine. He came up with the influential dopamine hypothesis of schizophrenia, which held that schizophrenia involves abnormally elevated dopamine.
By presenting evidence that a major mental disorder could be understood in terms of neurotransmitter abnormalities, Snyder helped bring psychiatry into the modern world, with its idea that mental disorders should be thought of as brain disorders to be managed with pills.
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If it hadn’t been for the drug subculture of the 1960s, psychiatry might have taken a very different path.
A Broader Vision
The conception of mental illness that Snyder promoted—namely, that mental disorders are rooted in chemical imbalances in the brain—has not proved as successful as he and others hoped.
Neurotransmitter theories of mental illness have come and gone. For example, despite the popularity of the serotonin theory of depression, there’s little direct evidence that depression stems from a serotonin deficiency.
And despite the fame that Snyder’s dopamine hypothesis enjoyed, over the last four decades, the puzzle of schizophrenia has only grown more complex, not less. New research on drugs, neurotransmitters, and trauma has only deepened the mystery.
In the 1980s, a new generation of antipsychotic drugs like clozapine targeted a wider range of neurotransmitters than dopamine, suggesting that the link between dopamine and schizophrenia is more complex than we previously thought. Some even think the core culprit in schizophrenia is glutamate, and that dopamine problems represent a downstream effect.
We also now recognize that adverse childhood experiences can increase the likelihood of adult psychosis.
By better understanding psychiatry’s history, we can develop a more expansive picture of mental illness—one that goes far beyond neurotransmitters—and rethink what mental health practice should look like today.