Hallucinogen-Related Emergencies and Schizophrenia Risk

Over the past several decades, the public perception of psychedelics has swung back and forth. They’ve been seen as miraculous medicine at some times, morally dangerous substances at others. More recently, they have again resurfaced in the public consciousness as possible wonder drugs with vast therapeutic potential.

“They’re often perceived as healing molecules that have a narrative of love around them,” said Marco Solmi, M.D., Ph.D., research director in the psychiatry department at the University of Ottawa and medical director of Ottawa Hospital’s On Track First Episode Psychosis Program. “But we really don’t know much about them.”

In hopes of better understanding the safety profile of psychedelics, Solmi and colleagues conducted a population-based study in Ottawa. They found that individuals who required emergency care after using a hallucinogenic drug had a 21 times greater risk of developing a schizophrenia spectrum disorder (SSD) within three years compared with the general population. The findings were recently published in JAMA Psychiatry.

“There is generally a lack of knowledge of some of the potential adverse consequences related to hallucinogens, particularly when they’re used in what we would call a naturalistic setting,” said Daniel Myran M.D., M.P.H., the study’s lead author and an assistant professor of family medicine at the University of Ottawa.

The authors analyzed medical record data from 9.2 million individuals ages 14 to 65 enrolled in Ontario’s universal health insurance program between January 2008 and December 2021. They identified 5,217 individuals who had an ED visit involving hallucinogen use, which encompassed both dissociative drugs such as ketamine and psychedelics like LSD or psilocybin. Those who had an ED visit, hospitalization, or outpatient visit for psychosis in the five years prior to the hallucinogen-related ED visit were excluded.

The primary outcome was the development of an SSD, which was defined as a diagnosis of schizophrenia or schizoaffective disorder.

Individuals who had visited the ED due to hallucinogen use had a 21 times greater risk of developing an SSD within three years compared with the general population. After accounting for sociodemographic characteristics and comorbid mental and substance use disorders, those who had a hallucinogen-related ED visit still had a 3.5 times greater risk of developing an SSD. Further, individuals who had a hallucinogen-related ED visit had a greater risk of developing an SSD than individuals who had an ED visit related to alcohol or cannabis use.

Additional findings included:

Myran and Solmi stressed that the study does not establish a causal link between adverse reactions to hallucinogens and developing an SSD. They also pointed out that the data they studied did not include detailed information on the type of hallucinogens used—an area that requires further research.

“Even in clinical trials, the experience of taking a psychedelic is not easy,” Myran said. “The patients themselves say it is really challenging. We need to move beyond the idea that we can run trials that will tell us if these drugs are safe and start doing more studies of varying designs to monitor for adverse effects that occur outside of trials.”

Natalie Gukasyan, M.D., an assistant professor of psychiatry at Columbia University, who was not involved with the study, said that its findings were unsurprising. Patients who have one psychotic episode, even if it is substance induced, are at a higher risk of having another episode in the future. “But I haven’t seen data to confirm that to this population level before, so that was interesting,” said Gukasyan, who was previously at Johns Hopkins Center for Psychedelic and Consciousness Research.

“We are in a time when a lot more people are interested in psychedelics,” she said. “This kind of data suggests that we as clinicians should be asking our patients, especially young patients, if they’re planning to use a psychedelic, so we can help them understand what their risks might be.”

The study was funded by a grant from the Ontario Ministry of Health and Ministry of Long-Term Care. ■