Psilocybin Therapy for Alcohol Use Disorder and Depression
Article Title: “Psilocybin in Alcohol Use Disorder and Comorbid Depressive Symptoms: Results from a Feasibility Randomized Clinical Trial”
Authors: Amandine Luquiens, Dahbia Belahda, Carine Graux, Noe Igounenc, Chris Serrand, Paul Rochefort, Thibault Mura, Felix Sergent
Publication Date: July 2025
Background
Alcohol Use Disorder (AUD) is a chronic and relapsing condition, frequently accompanied by depression. Both conditions share overlapping mechanisms, with depression post-detoxification being a strong predictor of relapse. Yet, individuals with this dual diagnosis are often excluded from trials, leaving a gap in integrated treatment approaches. Psilocybin, a naturally occurring psychedelic compound, has shown promise in treating both depression and substance use disorders separately, but its effects on patients experiencing both simultaneously had not been studied until now.
Study Overview
This pilot randomised controlled trial was conducted in France and involved 30 recently detoxified inpatients diagnosed with severe AUD and moderate-to-severe depression. Participants received either two sessions of 25 mg psilocybin (n = 20) or a control dose of 1 mg (n = 10), spaced three weeks apart, alongside an intensive relapse prevention programme. The goal was to assess feasibility, safety, and preliminary efficacy for reducing alcohol use and depressive symptoms.
Participants were blinded to their dosage, as were the researchers. Preparatory and integration psychotherapy sessions framed each psychedelic dose, aligning with established therapeutic protocols for psychedelic use.
Key Findings
Feasibility & Retention: 95% of the 25 mg group completed both dosing sessions, compared to only 60% in the control group.
Abstinence Rates: At 12 weeks, 55% of the 25 mg group remained abstinent, compared to only 11% in the 1 mg group (p = 0.043).
Craving Reduction: The high-dose group reported significant reductions in craving frequency (p = 0.045).
Depression Response: 45% of the 25 mg group had an 80% or greater reduction in depression scores, compared to none in the control group (p = 0.027).
Safety: No serious treatment-related adverse events occurred. Anxiety during dosing was brief and well-managed; most participants tolerated the sessions well.
Blinding Integrity: Most participants correctly guessed their group, highlighting the challenge of blinding in psychedelic studies.
Discussion
Though small in scale, the study demonstrated a clear interest and high retention for psilocybin treatment among a complex patient group. Importantly, the findings support psilocybin’s potential not just in reducing drinking behaviour, but also in significantly improving mood, a crucial factor in preventing relapse. While antidepressants were allowed during the trial, they did not appear to hinder psilocybin’s effectiveness.
Preparation and integration sessions followed a structured manual that incorporated mindfulness and Acceptance and Commitment Therapy (ACT), potentially contributing to the low anxiety levels reported during dosing sessions. The study also highlighted the importance of offering more equitable representation, with 43% of participants being women, an improvement over previous psychedelic trials.
Implications
This study offers early evidence that psilocybin, when combined with psychotherapy, can be a viable, safe and potentially effective treatment option for patients facing both AUD and depression. This is of importance as it opens a new potential healing path to an underserved group with limited integrated therapies available.
Potential Application
Psychedelic retreat centres and therapeutic clinics could draw upon this evidence to support tailored, dual-diagnosis protocols, especially for clients with both substance use and mood disorders. Incorporating structured preparation, careful dosing, and post-session integration could mirror the supportive design of this trial. The use of psilocybin in a clinical or retreat setting should be positioned not just for addiction cessation, but as a broader tool for emotional reset and healing.
Conclusions
This pioneering study adds valuable data to the growing evidence base for psychedelic-assisted psychotherapy. While further research with larger samples is needed, the results suggest that psilocybin may offer a meaningful new treatment pathway for individuals with co-occurring alcohol use disorder and depression.
Reference:
Luquiens, A., Belahda, D., Graux, C., Igounenc, N., Serrand, C., Rochefort, P., Mura, T., & Sergent, F. (2025). Psilocybin in alcohol use disorder and comorbid depressive symptoms: Results from a feasibility randomized clinical trial. Addiction. https://doi.org/10.1111/add.70152
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