Hallucinogen-Related ER Visit Linked to Increased Schizophrenia Risk

A new study found people with a hallucinogen-related emergency department visit had a 3.5-fold increased risk of developing schizophrenia compared to the general population.¹

Psychedelics have grown in popularity in recreational and therapeutical contexts, particularly with the recent anticipation surrounding the US Food and Drug Administration’s decision on MDMA for PTSD treatment, which ultimately resulted in a Complete Response Letter (CRL) this past August.² Research indicates that hallucinogen use has been rising rapidly since the mid-2010s in the US. As this recent study suggested, hallucinogens, such as MDMA, psilocybin, LSD, DMT, and MDMA, may have potential implications for mental health.

“Our findings underscore a concerning link between hallucinogen use that requires care in the emergency room and increased risk of schizophrenia,” said lead investigator Daniel Myran, MD, MPH, the Canada research chair in social accountability at the University of Ottawa, in a statement.³ “While there is enormous enthusiasm for psychedelic-assisted therapy as a new mental health treatment, we need to remember how early and limited the data remains for both the benefits and the risks.”

In a population-based, retrospective cohort study, the team followed 9,244,292 individuals aged 14 – 65 years (mean age: 40.4 years; 50.2% female) living in Ontario, Canada from 2008 – 2021 for a median of 5.1 (IQR, 2.3 – 8.6) years.¹ In total, 5217 participants (0.1%) had an emergency department visit involving hallucinogen use and 9,239,075 (99.9%) did not. The most common emergent department visits involving hallucinogen use were harmful use (36.6%), acute intoxication (22.2%), dependence or withdrawal (12.7%), and hallucinogen-induced psychosis (3.5%).

Compared with the general population, individuals who had emergency department visits involving hallucinogen use were more likely to be younger (mean age: 26.69 years vs 40.37), male (70.8% vs 49.8%), live in low-income neighborhoods (27.9% vs 18.9%), and be a long-term Canada resident (91.8% vs 80.1%).

Myran and colleagues examined the changes in the number of emergency department visits involving hallucinogens over time, as well as the risk of a schizophrenia diagnosis after the visits, from May-August 2024.

Investigators observed a stable annual rate of emergency department visits involving hallucinogens from 2008 – 2012, and this rate increased by 86% from 2013 – 2021. Within 3 years of an emergency department visit involving hallucinogens, those with a hallucinogen-related emergency department visit had a 21-fold increased risk of developing schizophrenia (4%) compared with the general population (0.15%) (age- and sex-adjusted hazard ratio [HR], 21.32; 95% confidence interval [CI], 18.58 – 24.47). After adjusting for co-occurring substance use and mental health disorders, the study found a 3.5-fold increased risk of schizophrenia (HR, 3.53; 95% CI, 3.05 – 4.09).

Participants with emergency department visits involving hallucinogens were at 4.7- and 1.5-times greater risk of schizophrenia compared with individuals with emergency department visits involving alcohol (HR, 4.66; 95% CI, 3.82 – 5.68) and cannabis (HR, 1.47; 95% CI, 1.21 – 1.80), respectively.

Investigators emphasized that the findings do not establish a causal link between hallucinogen use and schizophrenia—more research is needed. The study does suggest hallucinogen use may make individuals susceptible to psychosis or schizophrenia.

“Clinical trials of psychedelic-assisted psychotherapy have safeguards, such as excluding individuals with a personal or family history of schizophrenia and close monitoring while participants use hallucinogens,” Myran said.³ “Our findings provide a timely caution about potential risks of hallucinogen use outside of trial settings.”

References

1. ^{Myran DT, Pugliese M, Xiao J, et al. Emergency Department Visits Involving Hallucinogen Use and Risk of Schizophrenia Spectrum Disorder. JAMA Psychiatry. Published online November 13, 2024. doi:10.1001/jamapsychiatry.2024.3532}
2. ^{Derman, C. FDA Rejects Application for MDMA-Assisted Therapy in PTSD, Calls for Additional Trial. HCPLive. August 9, 2024. https://www.hcplive.com/view/fda-rejects-application-for-mdma-assisted-therapy-in-ptsd-calls-for-additional-trial. Accessed November 14, 2024.}
3. ^{Psychedelic use linked to increased risk of schizophrenia, study finds. EurekAlert! November 13, 2024.}