REVIEW OF: Myran DT et al, JAMA Psychiatry 2024;82(2):142–150

STUDY TYPE: Retrospective cohort study

A surge of interest in hallucinogens has led to a sharp increase in usage, with Americans ages 19–30 using them at more than twice the rate in 2023 compared to 2015. This is despite their legal status (or lack thereof) and limited research on their potential adverse effects. This study adds further context.

A population-based, retrospective cohort examination of emergency department (ED) health records from Ontario, Canada followed over 9 million individuals ages 14–65 with no history of psychosis for a median of approximately 5 years. The study covered 2008–2021, capturing the uptick in hallucinogen use. Researchers compared the future diagnosis of schizophrenia among those with any hallucinogen-related ED visit to those without. To reduce potential confounders, patients were compared to both the general population and to people with an ED visit involving either alcohol or cannabis.

During this time, 5,217 people had an ED visit related to hallucinogens. They were younger than average (26.7 vs 40.4 years), more often male (71% vs 50%), and more frequently from low-income neighborhoods. People with a hallucinogen-related ED visit had 3.5 times higher risk of developing schizophrenia within 3 years compared to the general population. Hallucinogen-induced psychosis correlated with a 14.66-fold increased risk of schizophrenia compared to the general population. The risk of schizophrenia was also greater than those with ED visits involving alcohol (hazard ratio [HR]=4.66) or cannabis (HR=1.47).

Critics of this study argued that the ED records included PCP among hallucinogens when it is usually thought of as a dissociative, and that polysubstance use could have colored the results. 

CARLAT TAKE

Individuals who experience adverse effects from hallucinogens that are severe enough to require an ED visit have an increased risk of developing schizophrenia. This study does not clarify the direction of causation, but there’s a real possibility that hallucinogens cause schizophrenia in vulnerable patients. Media attention has given psychedelics an aura of safety, but remember that patients with bipolar disorder or a family (or personal) history of psychosis were excluded from most psychedelic trials. Those patients should not experiment with psychedelic therapy.