The Man Who Made Schizophrenia in a Lab
In 1969, a controversial experiment changed psychiatry's understanding of schizophrenia.
Posted April 13, 2026 | Reviewed by Devon Frye
American psychiatry didn’t develop its modern focus on diagnoses, brain chemistry, and medication by accident. It grew out of a series of bold ideas and experiments, many of which would be considered unethical today.
Perhaps one of the most striking involved the attempt to create schizophrenia in healthy volunteers. Among the researchers who pursued this idea was Burton Angrist, a young psychiatrist who used amphetamines to trigger temporary psychosis and, in doing so, helped reshape the field.
Desperate Times, Desperate Measures
In the late 1960s, psychiatry had no cure for schizophrenia. Antipsychotic drugs could help some patients manage symptoms, but they didn’t help everyone, and they often had severe side effects.
In a bid for progress, a group of scientists advanced an unusual conjecture: Instead of looking for a drug that cures schizophrenia, what if there were a drug that creates schizophrenia? If such a drug existed, they reasoned, it might offer two benefits.
First, doctors could take it themselves to better empathize with their patients. Second, by studying how the drug worked, researchers might get closer to understanding the biological roots of the illness.
In the 1950s, several psychiatrists experimented with LSD in hopes of inducing a “temporary schizophrenia.” By the early 1960s, that project had largely failed as researchers got better at distinguishing the features of LSD trips and schizophrenia symptoms.
But in the late 1960s, one doctor found a drug that seemed to do exactly what researchers had been looking for: amphetamines.
Amphetamine Psychosis
Burton Angrist was an assistant professor of psychiatry at NYU and a researcher in Bellevue Hospital’s psychiatric ward. By the early 1960s, he became painfully aware of the limits of talk therapy in helping his patients. He believed that if scientists could understand the biological mechanism of schizophrenia, they would be closer to a cure.
At the same time, Manhattan was in the midst of an amphetamine epidemic. Angrist began noticing a peculiar pattern: People who took large quantities of amphetamines, or used them for days on end, often developed a condition that was clinically indistinguishable from schizophrenia.
They heard menacing voices, experienced auditory hallucinations, and sometimes lost the logical coherence of their thoughts, speaking in riddles or nonsense. Doctors would often misdiagnose them with schizophrenia, only to watch the symptoms fade as the drug left their bodies.
It occurred to Angrist that amphetamines might be precisely the “madness‑mimicking” drug researchers had been seeking.
But there was a problem. How could he be sure the drug itself caused the psychosis? Perhaps the speed users who ended up at Bellevue had a latent form of schizophrenia that the drug merely triggered. Or perhaps the psychosis was caused by sleep deprivation, since many had been injecting amphetamines for days.
There was only one way to know for sure: give amphetamines to volunteers under controlled conditions and watch what happened.
In the spring of 1969, Angrist gathered four volunteers for his experiment. All were experienced speed users he had encountered at Bellevue. He brought each one individually to the psychiatric ward.
He knew it would be unsafe to give them large quantities of amphetamines at once, so he started each off with a small dose of 10 to 20 milligrams. An hour later, he gave them another dose, and a nurse checked their vital signs. Another hour, another dose, until they showed signs of psychosis.
One patient, known as Subject A, developed hallucinations and delusions within 20 hours. He believed a terrible stench emanated from his body and that people had been planted in a nearby building to watch him.
Another patient, Subject D, developed a powerful psychotic episode in which the flow of his thoughts lost all logical connection. He believed he was a prophet and wrote pages of nonsensical musings.
Thanks to Angrist’s work, amphetamine psychosis became widely accepted as a valid model of schizophrenia. More importantly, scientists began studying the mechanism of action of amphetamines in hopes of understanding schizophrenia itself.
The Dopamine Hypothesis of Schizophrenia
As I explore in my book , the use of amphetamines to create psychosis in the lab helped give rise to one of the most influential theories of schizophrenia: the dopamine hypothesis.
In 1970, the neuroscientist and psychiatrist Solomon Snyder, inspired by Angrist’s research, studied how amphetamines affect the brain. He realized that amphetamines induce psychosis by flooding the brain with dopamine.
That suggested to him that schizophrenia itself might be a dysfunction of dopamine.
Five years later, in 1975, his lab discovered the brain’s dopamine receptor and proved that all antipsychotic drugs work by blocking dopamine receptors. This led to a simple but compelling idea: One could turn schizophrenia on and off, like a light switch, by modulating dopamine.
Today, we know that the simple version of the dopamine hypothesis is incomplete. Schizophrenia involves a complex mesh of neurotransmitters, brain circuits, and life experiences. And “schizophrenia” itself is likely not a single illness but a cluster of related conditions. Yet Angrist’s experiment helped us better understand some aspects of it.
Burton Angrist’s Legacy
Burton Angrist went on to have a fruitful and productive career . He pioneered the early use of PET scans to study schizophrenia. He helped clarify how antipsychotic drugs worked. He played a major role in understanding the movement problems associated with early antipsychotic drugs and tested newer drugs that didn’t have those problems. He died in May 2024.
Years later, he acknowledged that his amphetamine experiment would likely be considered unethical today (Angrist 1994). He emphasized that ethical standards were different at the time, that he had exercised appropriate caution in protecting the volunteers, and that these were, after all, desperate times for psychiatry.
Despite the ethical questions it raised, Angrist’s experiment marked a critical turning point in our understanding of schizophrenia.
Angrist, Burton. 1994. “Ethical Issues Regarding Prospective Studies of Amphetamine Psychosis.” Journal of the California Alliance for the Mentally Ill
Duncan, Erica, John Rotrosen, and Adam Wolkin. 2024. “In Memoriam: Burton M. Angrist, MD.” Neuropsychopharmacology 49: 1947–48. https://doi.org/10.1038/s41386-024-01986-0
Garson, Justin. 2026. The Madness Pill: One Doctor’s Quest to Understand Schizophrenia . New York: St. Martin’s Press.
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Justin Garson, Ph.D., is a philosopher and author of The Madness Pill: One Doctor’s Quest to Understand Schizophrenia (St. Martin’s Press, 2026) and Madness: A Philosophical Exploration (Oxford, 2022).
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