Psilocybin-assisted psychotherapy for substance use disorders as a complex intervention: A systematic review of efficacy, mechanisms and psychotherapeutic frameworks
Lana Strika-Bruneau, Chérine Elhssaini, Baptiste Fauvel, Ewen Kervadec, Aurore Bezo, Ammar Amirouche, Amine Benyamina, Bruno Romeo
Journal of Psychopharmacology August 17, 2026 DOI: 10.1177/02698811261473436 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Individuals with primary substance use disorder diagnoses |
| Intervention | Psilocybin-assisted psychotherapy |
| Topics | Addiction Psilocybin Psychedelic-assisted therapy |
| Key findings | Psilocybin-assisted psychotherapy was associated with reductions in substance use, higher abstinence rates, and improved psychological well-being across 17 studies, though findings were heterogeneous. Trials combining repeated high-dose sessions with extended psychotherapeutic engagement consistently reported sustained benefits. The authors propose that outcomes arise from interactions among neurobiological, experiential, psychological, psychotherapeutic, and contextual processes. |
Abstract
Background: Psychedelic-assisted psychotherapy (PAP) shows promise for substance use disorders (SUDs), yet the respective contributions of pharmacological, experiential, psychotherapeutic, and contextual factors remain insufficiently understood.
Objective: To synthesize contemporary clinical evidence on PAP for SUDs, with particular attention to therapeutic frameworks, dosing strategies, safety, and mechanisms of action.
Methods: A systematic review of clinical studies published between 2000 and 2026 was conducted through structured database searches and manual surveillance. Eligibility criteria involved classic psychedelic administration within defined psychotherapeutic frameworks in individuals with a primary SUD diagnosis. Data were narratively analyzed and synthesized.
Results: Seventeen studies, encompassing 10 primary clinical trials, met inclusion criteria: ten focused on alcohol use disorder, five on tobacco use disorder, one on methamphetamine use disorder, and one on cocaine use disorder. All trials investigated psilocybin within structured psychotherapeutic protocols, primarily based on cognitive-behavioral and third-wave approaches. PAP was associated with reductions in substance use, higher abstinence rates, and improved psychological well-being, although findings remained heterogeneous and design-dependent. Trials combining repeated high-dose sessions with extended psychotherapeutic engagement consistently reported sustained clinical benefits. Findings further suggest that outcomes may arise from interactions between neurobiological, experiential, psychological, psychotherapeutic, and contextual processes.
Conclusion: Current evidence supports PAP as a promising but still emerging intervention for SUDs, although available clinical research remains exclusively based on psilocybin-assisted interventions. Findings further support conceptualizing PAP as a complex intervention embedded within an integrated psychotherapeutic process rather than as a pharmacological treatment alone. Larger controlled trials with active comparators, longer follow-up, and systematic investigation of psychotherapeutic and contextual mechanisms remain needed.
In the evidence
This study is part of the evidence base for 3 syntheses in the library. Here is how each one recorded it.
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Across 17 studies, psilocybin-assisted psychotherapy was associated with reductions in substance use, higher abstinence rates, and improved well-being, though findings were heterogeneous and design-dependent.
Synthesized
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Across 17 studies, psilocybin-assisted psychotherapy was associated with reductions in substance use, higher abstinence rates, and improved psychological well-being, though findings were heterogeneous and design-dependent.
Synthesized
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State of the evidence: Addiction Supports
Across 17 studies, psilocybin-assisted psychotherapy was associated with reductions in substance use, higher abstinence rates, and improved psychological well-being, though findings were heterogeneous and design-dependent, with sustained benefits in trials combining repeated high-dose sessions with extended psychotherapeutic engagement.
Synthesized
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 |