When LSD didn’t work, Burton turned to “amphetamine psychosis” and changed our understanding of the complex illness that affects approximately one in every 300 people today.
A controversial experiment carried out in 1969 in the United States marked a turning point in the history of psychiatry by helping to consolidate one of the most influential theories about: dopaminergic hypothesis.
Burton Angrist was a young psychiatrist who sought to induce temporary psychotic episodes in volunteers by giving them high doses of amphetamines. He said he wanted to better understand the biological mechanisms of the disease.
At the time, psychiatry was going through a period of great uncertainty, recalls Justin Garson in .
Available antipsychotics were able to alleviate some symptoms of schizophrenia in certain patients, but they did not work in all cases and were associated with serious side effects. It was out of necessity that some researchers wanted to find a substance capable of causing a state similar to schizophrenia, in the hope that this would illuminate the biological origin of the disorder.
Already during the 1950s, several psychiatrists had resorted to LSD hoping to induce “temporary schizophrenia”—efforts that lost steam as it became clearer that the drug’s effects did not, after all, correspond to the disease’s characteristic symptoms.
Link to amphetamine and dopamine
It was already in the late 1960s that Angrist, assistant professor of psychiatry at New York University and researcher at Bellevue Hospital, identified a possible more convincing model in amphetamines.
Angrist had seen the limits of psychotherapeutic approaches up close and was convinced that only a biological explanation of schizophrenia could pave the way for more effective treatments. At the same time, Manhattan was experiencing an epidemic of amphetamine use. And there was the pattern: people who consumed large quantities of the substance, or used it for several days in a row, developed clinical conditions practically indistinguishable from schizophrenia.
Consumers reported hearing voices, suffered auditory hallucinations and, in some cases, lost the logical coherence of their thoughts and began to speak in an incomprehensible way. They were often diagnosed with schizophrenia, until the symptoms disappeared as the drug left the body. For Angrist, amphetamines could be precisely the agent that researchers were looking for: a substance capable of temporarily reproducing psychosis.
But could the drug itself be the cause of psychosis? Or were those consumers already predisposed to schizophrenia, and the substance a triggering factor? And the symptoms could result from sleep deprivationas many spent days in a row using amphetamines, without sleeping.
In the spring of 1969, the specialist gathered four volunteers, all avid amphetamine users. Each one was individually subjected to the experiment in a psychiatric ward. He started with relatively small doses, between 10 and 20 milligrams, administered progressively over the hours. Between each dose, a nurse monitored vital signs until psychotic symptoms appeared.
One of the participants reportedly began hallucinating and delirious after 20 hours, convinced that his body gave off a terrible smell and that he was being watched by people installed in a nearby building. Another developed an intense psychotic episode, in which his thoughts lost any logical connection: he believed he was a prophet and filled pages with meaningless texts.
The call “amphetamine psychosis” From then on, it became widely accepted as an experimental model of schizophrenia. And it opened the way for a new line of investigation into the dopamine.
In 1970, inspired by Angrist’s work, neuroscientist and psychiatrist Solomon Snyder concluded that amphetamines caused psychosis by flooding the brain with dopamine. From then on, the idea that schizophrenia could result from a dysfunction of this neurotransmitter gained strength.
Five years later, Snyder identified the dopamine receptor in the brain and demonstrated that all antipsychotics worked by blocking these receptors. The dopaminergic hypothesis has become central in modern psychiatry, although it is now recognized that it is insufficient to explain, by itself, the complexity of schizophrenia, which involves multiple neurotransmitters, brain circuits and life factors.
Burton Angrist, who died in May 2024, would later acknowledge that this experiment would hardly be considered ethical by today’s standards, but the study went down in history as a decisive moment in the scientific understanding of psychosis and the evolution of biological psychiatry.
