Psychedelics for the Treatment of Substance Use Disorders

An umbrella review of 13 systematic reviews and meta-analyses examined the efficacy of classic and non-classic psychedelics (LSD, psilocybin, ayahuasca, mescaline, and ibogaine) for treating substance use disorders, including alcohol, tobacco, opioid, and cannabis use disorders. Only two reviews performed meta-analyses; the rest provided narrative syntheses. Twelve reviews were rated critically low in methodological quality, and one was rated low. While some reviews reported promising effects, particularly for alcohol use disorder, others concluded the evidence remains inconclusive or inconsistent. Overlap of primary studies across reviews was slight. The overall evidence base is limited by methodological weaknesses and inconclusive results.

Study at a glance

Abstract

Abstract: Background: Psychedelic-assisted therapy is increasingly being explored as potential treatment for substance use disorders (SUDs). While multiple systematic reviews and meta-analyses have examined this topic, the efficacy, method­ological quality, and overlap of the existing evidence base remain unclear. Methods: We conducted an umbrella review of systematic reviews and meta-analyses evaluating the efficacy of classic and non-classic psychedelics for the treatment of SUDs. Searches were performed in PubMed and Web of Science up to April 16, 2025. Methodological quality was assessed using the AMSTAR 2 tool and overlap across primary studies was quantified using the Corrected Covered Area (CCA) method. Results: 13 systematic reviews comprising 105 unique primary studies (excluding follow-up analyses) were included. Investigated substances included LSD, psilocybin, ayahuasca, mescaline, and ibogaine, targeting alcohol, tobacco, opioid, and cannabis use disorders as well as unspecific and polyvalent drug use. Only two reviews conducted meta-analyses; the remainder provided narrative syntheses. 12 reviews were rated as critically low in methodological quality, and one as low. Frequent shortcomings included missing protocol registration, insufficient justification of publication restrictions, and absence of excluded studies lists. While several reviews reported promising effects – particularly for alcohol use disorder – others concluded that the evidence remains inconclusive or inconsistent. According to CCA a slight overlap of primary studies across reviews was observed. Conclusion: Despite some encouraging findings, the overall evidence base for psychedelic-assisted therapy in SUDs is limited by methodological weaknesses and inconclusive results. More high-quality primary studies and rigorous systematic reviews are needed to establish a reliable foundation for clinical application.