Effects of psychedelics on opioid use disorder: a scoping review of preclinical studies.
Alejandra Pulido-Saavedra, Henrique Nunes Pereira Oliva, Tiago Paiva Prudente, Razi Kitaneh, Eric J Nunes, Colleen Fogg, Melissa C Funaro, Jeremy Weleff, Anahita Bassir Nia, Gustavo A Angarita
Cellular and Molecular Life Sciences January 21, 2025 DOI: 10.1007/s00018-024-05519-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Preclinical animal studies |
| Topics | Addiction |
| Keywords | Conditioned place preference Self-administration Withdrawal Psychedelics hallucinogens Entheogens Psychedelic compounds Drug rehabilitation Recovery Opioid dependence |
| Citations | 5 |
| Key findings | Most preclinical studies found that ibogaine, noribogaine, 18-MC, and ketamine reduced opioid self-administration, withdrawal, and conditioned place preference, but seven studies showed no improvement over controls. |
Abstract
The current opioid crisis has had an unprecedented public health impact. Approved medications for opioid use disorder (OUD) exist, yet their limitations indicate a need for innovative treatments. Limited preliminary clinical studies suggest specific psychedelics might aid OUD treatment, though most clinical evidence remains observational, with few controlled trials. This review aims to bridge the gap between preclinical findings and potential clinical applications, following PRISMA-ScR guidelines. Searches included MEDLINE, Embase, Scopus, and Web of Science, focusing on preclinical in vivo studies involving opioids and psychedelics in animals, excluding pain studies and those lacking control groups. Forty studies met criteria, covering both classic and non-classic psychedelics. Most studies showed that 18-methoxycoronaridine (18-MC), ibogaine, noribogaine, and ketamine could reduce opioid self-administration, alleviate withdrawal symptoms, and change conditioned place preference. However, seven studies (two on 2,5-dimethoxy-4-methylamphetamine (DOM), three on ibogaine, one on 18-MC, and one on ketamine) showed no improvement over controls. A methodological quality assessment rated most of the studies as having unclear quality. Interestingly, most preclinical studies are limited to iboga derivatives, which were effective, but these agents may have higher cardiovascular risk than other psychedelics under-explored to date. This review strengthens support for translational studies testing psychedelics as potential innovative targets for OUD. It also suggests clinical studies need to include a broader range of agents beyond iboga derivatives but can also explore several ongoing questions in the field, such as the mechanism of action behind the potential therapeutic effect, safety profiles, doses, and frequency of administrations needed.
Comparable studies
Other systematic reviews and meta-analyses on addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Mindfulness Meditation for Substance Use Disorders: A Systematic Review Individuals with substance use disorders | 2009 | Systematic review | |
| Mindfulness-Based Interventions for the Treatment of Substance and Behavioral Addictions: A Systematic Review | 2018 | Systematic review | |
| Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review | 2021 | Systematic review | |
| Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials Patients with psychiatric disorders, primarily alcoholism | 2020 | Systematic review | n = 567 |
Citations in the library
Cited by 6
- Classic Psychedelics in Pain Modulation: Mechanisms, Clinical Evidence, and Future Perspectives ACS Chemical Neuroscience June 6, 2025
- The transformational power of psychedelics: catalysts for creativity, consciousness, and mental health. Molecular Psychiatry September 30, 2025
- “I can objectively view my trauma without feeling like I'm there”: Reddit discussions on self-reported use of psychedelics to address co-occurring substance use and mental health needs Journal of Psychedelic Studies March 30, 2026
- The combination of exercise and psychedelics for the treatment of major depressive disorder Discover Mental Health March 7, 2026
- Differential effects of psilocybin derivatives on fentanyl-induced conditioned place preference in male and female mice. Journal of Psychopharmacology August 30, 2026
and 1 more in the library
Cites 68
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Long-term follow-up of psilocybin-facilitated smoking cessation The American Journal of Drug and Alcohol Abuse July 21, 2016
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
- The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects. ACS Pharmacology & Translational Science December 10, 2020
and 63 more in the library