Your new experience awaits. Try the new design now and help us make it even better

ORIGINAL RESEARCH article

Front. Psychiatry

Sec. Addictive Disorders

Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1648104

This article is part of the Research TopicEmerging Treatment Approaches for Substance Use DisordersView all 8 articles

Associations between psychedelic use and adverse outcomes in substance use disorders: a real-world EHR-based cohort study

Provisionally accepted
Fares  QeadanFares Qeadan1*Ashlie  McCunnAshlie McCunn1Benjamin  TingeyBenjamin Tingey1Paul  ThielkingPaul Thielking2
  • 1Loyola University Chicago, Chicago, United States
  • 2University of Utah Health Huntsman Mental Health Institute, Salt Lake City, United States

The final, formatted version of the article will be published soon.

Aims: To examine associations between psychedelic use and adverse health outcomes, including overdose, relapse, mental health crises, and hospitalizations, among individuals with substance use disorders (SUD), and to compare these outcomes across different treatment modalities including anesthetics and outpatient SUD services. Design: Retrospective cohort study using propensity score-weighted quasi-Poisson regression models to estimate adjusted incidence rate ratios (aIRRs). Setting: Data were drawn from Oracle EHR Real-World Data™ comprising 138 U.S. health systems restricted to those ≥12 years old from January 1, 2000, to August 31, 2023. Participants: 3,209,798 patients with a documented SUD diagnosis from 2000 to 2023. Patients with a prior history of psychedelic use or hallucinogen-related diagnoses were excluded. The final cohort included 8,514 new psychedelic users and over 3.2 million non-users. Measurements: Exposures were captured during a 3-month post-index period and included outpatient psychedelic prescriptions or procedures (primarily ketamine), general anesthetic outpatient prescriptions, and outpatient SUD services. Outcomes, assessed over 2 years, included SUD-related hospitalizations/emergency department (ED) visits, mental health crises, all-drug overdoses, and relapse. Propensity scores accounted for demographic, clinical, and behavioral confounders. Findings: Psychedelic use was associated with significantly reduced rates of all adverse outcomes, including all-drug overdose (aIRR = 0.48; 95% CI: 0.37-0.63), relapse (aIRR = 0.68; 0.60-0.77), SUD hospitalizations/ED visits (aIRR = 0.76; 0.69-0.82), and mental health crises (aIRR = 0.82; 0.73-0.92), compared to no treatment. The combination of psychedelics, anesthetics, and outpatient services was associated with the strongest reduction in mental health crises (aIRR = 0.21; 0.06-0.77). Trends were consistent in sensitivity analyses including patients with mental health conditions and comparisons to medication-assisted treatment. Conclusions: In this large national cohort, psychedelic use, particularly when combined with anesthetic and outpatient care, was associated with reduced adverse health outcomes among people with SUD. These findings support further investigation into psychedelic-based interventions within integrated treatment frameworks.

Keywords: psychedelics, Ketamine, substance use disorder, Real-world evidence, Electronic Health Records, Drug Overdose, Mental Health, relapse

Received: 16 Jun 2025; Accepted: 29 Sep 2025.

Copyright: © 2025 Qeadan, McCunn, Tingey and Thielking. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Fares Qeadan, fqeadan@luc.edu

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.