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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Topics | Addiction Ayahuasca Ibogaine Ketamine LSD Psilocybin |
| Keywords | Psychedelics Psychedelic treatment Drug rehabilitation Recovery Opioid dependence |
| Citations | 4 |
| Key findings | 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.
In the evidence
This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.
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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.
Synthesized
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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 and high risk of bias.
Synthesized
Comparable studies
Other systematic reviews and meta-analyses on ayahuasca for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans | 2016 | Systematic review | |
| Effects of ayahuasca and its alkaloids on substance use disorders: an updated (2016-2020) systematic review of preclinical and human studies. Rodents and humans (healthy ritual ayahuasca users and patients with substance use... | 2022 | Systematic review | n = 9 |
| Psychedelic Treatments for Substance Use Disorder and Substance Misuse: A Mixed Methods Systematic Review Adults with substance use disorder or substance misuse | 2023 | Systematic review | |
| [Efficacy of psychedelics in psychiatry, a systematic review of the literature]. Patients with psychiatric conditions (anxiety, depression, major depressive disorder,... | 2021 | Systematic review | n = 25 |
| The current state of ayahuasca research in animal models: A systematic review. Rodents, primates, and zebrafish | 2023 | Systematic review | n = 32 |