Evaluating the Effectiveness of Psychedelic-Assisted Therapy in Treating Alcohol Use Disorders: A Review

ABSTRACT Background Alcohol Use Disorder (AUD) is a widespread condition with serious health, social, and economic impacts, often marked by relapse despite the availability of FDA-approved treatments. Recent studies suggest that psychedelic substances, such as psilocybin, Lysergic acid diethylamide (LSD), ayahuasca, etc. may offer novel therapeutic potential in treating AUD by modulating neurotransmission and promoting neuroplasticity. Ketamine is a dissociative psychedelic, and it works primarily by blocking NMDA receptors (a type of glutamate receptor in the brain) compared to Classic psychedelics (like LSD, psilocybin, mescaline) work mainly by activating serotonin 5-HT2A receptors hence ketamine was not the focus of this review. This narrative review aims to synthesize existing evidence on the effectiveness of psychedelic-assisted therapy for AUD.

Methods: A systematic literature search was conducted across PubMed and Google Scholar, yielding 186 articles. Following inclusion and exclusion criteria, 71 studies were selected for review, including randomized controlled trials, observational studies, and meta-analyses. These studies assessed the use of psychedelics (e.g. LSD, psilocybin) in individuals with AUD, focusing on therapeutic outcomes, neurobiological mechanisms, and safety profiles.

Results: Findings from clinical trials and observational studies suggest that psychedelic therapies, particularly those involving psilocybin and LSD, are associated with significant reductions in alcohol consumption, enhanced emotional regulation, and sustained improvements in mental health over follow-up periods ranging from 6 to 32 weeks. These effects are thought to be mediated by serotonin 2A receptor agonism, which promotes neuroplasticity in regions such as the prefrontal cortex, enhancing cognitive and emotional processes. A meta-analysis of six trials revealed that a single dose of LSD outperformed traditional pharmacotherapies like naltrexone and acamprosate in promoting long-term abstinence from alcohol.

Conclusion: This review emphasizes the potential of psychedelic-assisted therapy as a promising alternative or adjunctive treatment for AUD. Psychedelic substances, particularly when combined with behavioral therapies such as Motivational Enhancement Therapy (MET), show significant promise in reducing alcohol misuse and fostering long-term recovery. Despite the promising results, further research is needed to assess the safety, long-term efficacy, and optimal treatment protocols, particularly regarding patients with underlying psychiatric conditions. Future studies should focus on large-scale, controlled trials with neuroimaging and long-term follow-up to fully elucidate the neurobiological mechanisms underlying these therapeutic effects and to establish best practices for clinical use.