Efficacy and safety of psilocybin for the treatment of substance use disorders: A systematic review.
Shakila Meshkat, Gunjan Malik, Richard J. Zeifman, Jennifer Swainson, Krishna Balachandra, Amy C. Reichelt, Yanbo Zhang, Lisa Burback, Olga Winkler, Andrew J. Greenshaw, Eric Vermetten, Leah M. Mayo, Robert Tanguay, Rakesh Jetly, Venkat Bhat
Neuroscience & Biobehavioral Reviews June 1, 2025 DOI: 10.1016/j.neubiorev.2025.106163 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Double-blind Open-label Cross-sectional Qualitative Peer reviewed |
|---|---|
| Intervention | Psilocybin-assisted psychotherapy |
| Dose | microdosing to 20-40 mg/70 kg |
| Topics | Psilocybin Psychedelic-assisted therapy Addiction |
| Keywords | Addiction treatment Substance use disorders Systematic review Psilocybin research Substance abuse treatment Mental health interventions |
| Citations | 11 |
| Key findings | Preliminary evidence supports psilocybin's efficacy and safety for alcohol and tobacco use disorders, particularly when combined with psychotherapy. |
Abstract
Psilocybin, a serotonergic psychedelic, may have therapeutic benefits for Substance Use Disorders (SUDs), but its overall efficacy and safety remain uncertain. This systematic review assessed the safety and efficacy of psilocybin for SUDs through a systematic database search conducted via OVID on May 22, 2024, and summarized 26 ongoing clinical trials registered on clinicaltrials.gov. Among 16 published included studies, 7 (43.75 %) focused on Alcohol Use Disorder (AUD), 5 (31.25 %) on Tobacco Use Disorder (TUD), and the remainder on Cocaine Use Disorder (CUD) (1, 6.25 %), Opioid Use Disorder (1, 6.25 %), Nicotine Use Disorder (1, 6.25 %), and multiple SUDs (1, 6.25 %). Study designs included open-label trials (5, 31.25 %), cross-sectional observational studies (6, 37.5 %), qualitative analyses (2, 12.5 %), one double-blind RCT (6.25 %), one pilot fMRI study (6.25 %), and one long-term follow-up (6.25 %). Psilocybin-assisted psychotherapy (PAP) was used in 10 studies (62.5 %), with doses ranging from microdosing to 20-40 mg/70 kg. PAP was associated with significant reductions in alcohol consumption, smoking cessation, and related psychological improvements. AUD studies reported fewer heavy drinking days, increased abstinence rates, and neuroimaging data indicating normalization of brain activity. TUD studies demonstrated high smoking abstinence rates, with mystical experiences predicting long-term outcomes. Findings for other SUDs were mixed, though psilocybin showed potential in reducing opioid dependence and nicotine use. Preliminary evidence supports psilocybin's efficacy and safety for AUD and TUD, particularly with psychotherapy, but larger clinical trials are needed to confirm these findings.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Therapeutic effect of psilocybin in addiction: A systematic review Patients with alcohol use disorder or tobacco use disorder | 2023 | Systematic review | n = 151 |
| Psilocybin-Assisted Therapy: A Review of a Novel Treatment for Psychiatric Disorders Patients with psychiatric disorders related to anxiety, depression, and substance use | 2017 | Systematic review | n = 7 |
| The intensity of the psychedelic experience is reliably associated with clinical improvements: A systematic review and meta-analysis. Patients treated with classical psychedelics | 2025 | Meta-analysis | |
| Psychedelic‐assisted treatment for substance use disorder: A narrative systematic review Participants in studies of psychedelic-assisted treatment for alcohol, tobacco, and... | 2025 | Systematic review | n = 2,035 |
| 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 |
Citations in the library
Cited by 11
- Ketamine, Psychedelics, and Psychotherapy: Reframing, Redefining, Renaming Treatment Models. The Canadian Journal of Psychiatry October 28, 2025
- Efficacy and safety of psilocybin-assisted therapy for alcohol use disorder: A systematic review and meta-analysis Journal of Psychopharmacology October 8, 2026
- Psychedelics and longevity: implications for lifespan, healthspan and functional aging Longevity July 5, 2026
- Naturally Derived Psilocybin for Therapeutic Use: A Six-Criterion Framework for Evidence, Safety, and Benefit–Risk Considerations in Policy and Clinical Development Biomolecules July 3, 2026
- Psilocybin as a Transdiagnostic Treatment for Eating Disorders and Comorbid Psychopathology: Implications for Clinical Nosology and Research Directions International Journal of Eating Disorders July 2, 2026
and 6 more in the library
Cites 38
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Journal of Psychopharmacology September 11, 2014
and 33 more in the library