The therapeutic effects of psychedelics for opioid use disorder: A systematic review of clinical studies.
Jeremy Weleff, Alejandra Pulido-Saavedra, Ardavan Mohammad Aghaei, Kevin Ing, Miranda Arakelian, Rodrigo Fontenele, Neil Nero, Brian S Barnett, Akhil Anand, Anahita Bassir Nia, Gustavo A Angarita
Psychiatry research June 1, 2025 DOI: 10.1016/j.psychres.2025.116446 via PubMed
Summary
AI-generated from the abstractA systematic review of clinical studies on psychedelics for opioid use disorder found few completed trials using serotonergic psychedelics; most investigated ibogaine or ketamine. The evidence is limited by weak study designs focused on opioid withdrawal, few double-blind or placebo-controlled trials, and considerable methodological heterogeneity that makes comparisons across compounds difficult. Most studies had a high risk of bias, mainly due to lack of randomization, blinding, and blinded outcome assessment. The review outlines these limitations and steps to improve the quality of future research in this area.
Study at a glance
| Characteristics | Systematic review Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Topics | Addiction Ayahuasca Ibogaine Ketamine LSD Psilocybin |
| Citations | 4 |
| Key finding | Few clinical studies have been completed using serotonergic psychedelics for opioid use disorder, with most investigating ibogaine or ketamine, and the evidence is limited by weak study designs, few double-blind trials, and high risk of bias. |
Abstract
Opioid-related overdose deaths have reached record high levels, and novel treatments for opioid use disorder (OUD) are needed. The three United States Food and Drug Administration (FDA)-approved medications for OUD function primarily at the mu-opioid receptor. While these remain the gold-standard treatment for OUD, they have shortcomings and treatment options separate from the opioid receptor system deserve attention. Preclinical, clinical, and naturalistic studies of psychedelics have shown some evidence that they may reduce opioid and other substance use. Here, we present the results of a systematic review of clinical studies investigating the therapeutic applications of psychedelics for OUD to describe the current state of the literature and guide future clinical study design in this area. Findings indicate few studies completed using serotonergic psychedelics, with most investigating ibogaine or ketamine. In addition, findings are limited by many studies of weak design focused on opioid withdrawal, and few double-blind or placebo-controlled trials with considerable methodological heterogeneity making comparisons difficult across compounds. Most studies were found to have a high risk of bias mostly related to lack of randomization, blinding, and blinding of assessment outcomes. We outline these limitations and steps towards improving the quality of future studies of psychedelics for OUD.