This double-blind, randomised controlled pilot study (n=30) found that psilocybin-assisted psychotherapy psilocybin (25mg; 2x; n=20) showed significantly higher abstinence rates at 12 weeks (55% vs 11%) compared to placebo (1mg; n=10) in patients with severe alcohol use disorder (AUD) and depression (MDD) who had recently completed detoxification.
Abstract of Psilocybin in alcohol use disorder and comorbid depressive symptoms
“Background and Aims: Psilocybin has emerged as a potential treatment for alcohol use disorder (AUD), but early efficacy data are inconsistent. Depression following alcohol detoxification significantly increases the risk of relapse. This pilot study aimed to evaluate the feasibility, acceptability, and preliminary efficacy of psilocybin-assisted psychotherapy for patients with comorbid AUD and depression.
Design: A prospective, single-center, double-blind, parallel (2:1), randomized controlled pilot study.
Setting: The study was conducted in a French inpatient addiction treatment program offering intensive relapse prevention interventions.
Participants: Of 350 screened patients, 30 adults (mean age 49 ± 10 years; 43% female) with severe AUD (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5] criteria) and a Beck Depression Inventory-II (BDI-II) score ≥14 were included. Participants had completed detoxification between 14 and 60 days prior to inclusion.
Interventions: Participants received either two oral sessions of 25 mg (n = 20) or 1 mg (n = 10) psilocybin-assisted psychotherapy spaced three weeks apart, as an add-on to standard care. Patients, investigators and outcome assessors were all blinded to patient group.
Measurements: The primary outcome was feasibility, according to participation in both dosing sessions and recruitment/inclusion rates. Secondary outcomes included alcohol use (Alcohol Timeline Followback), time to relapse, craving (Craving Experience Questionnaire), depression (BDI-II), safety and blinding integrity.
Findings: One participant in the 25 mg group could not receive the second dose due to myocardial infarction occurring three days earlier, unrelated to the treatment. Four participants in the control group refused the second session after guessing their group assignment (p-value = 0.019), with one participant self-administering 3,4-Methylenedioxymethamphetamine (MDMA). At 12 weeks, the 25 mg group showed significantly greater abstinent rate (11/20 (55%) vs 1/9 (11%) (one lost of follow up) (difference = −44%, [95% confidence interval [CI]: −82% to −5.9%]), p = 0.043), reductions in % drinking days −100 (−100 to −49) vs − 93 (−96 to 0), p = 0.038 and craving frequency −8 (−23 to −1) vs + 7 (−2 to 11), p = 0.045, respectively in the 25 vs 1 mg groups (median [25;75]). Relapse rates were 35% in the 25 mg group and 50% in the control group (HR = 0.52 [0.16 to1.65]). No efficacy differences were observed based on antidepressant use in terms of drinking and depression. Blinding was imperfect (correct guess by patients: 93.3%; investigators: 86.7%). Twenty-five adverse events were reported in 10 patients (50%) in the 25 mg group versus 6 patients (60%) in the control group.
Conclusions: Psilocybin-assisted psychotherapy appears feasible, acceptable, and safe in recently detoxified patients with comorbid alcohol use disorder and depression.“
Authors: Amandine Luquiens, Dahbia Belahda, Carine Graux, Noe Igounenc, Chris Serrand, Paul Rochefort, Thibault Mura & Felix Sergent
Summary of Psilocybin in alcohol use disorder and comorbid depressive symptoms
Alcohol use disorder (AUD) is one of the leading causes of preventable death and contributes significantly to global morbidity. It is often marked by a chronic relapsing course, with relapse rates estimated at 40–60%. Co-occurring psychiatric conditions, particularly depression, are common and exacerbate the severity and prognosis of AUD. Individuals with both AUD and depression, often referred to as having a “dual disorder”, tend to have worse treatment outcomes, including a heightened risk of relapse, compared to those with AUD alone. Despite this, such individuals are frequently excluded from clinical trials and remain underrepresented in treatment interventions.
Depressive symptoms often persist after alcohol detoxification and can significantly impair recovery. These symptoms are associated with dysregulation in the brain’s reward system, increased sensitivity to stress, and continued craving for alcohol. Depression may also contribute to emotional distress that can trigger relapse. Previous studies have noted that up to 60% of individuals with both AUD and depression relapse within three months of completing detoxification. The researchers aimed to explore a treatment strategy that targets both disorders simultaneously, in recognition of their shared behavioural and neurobiological mechanisms.
Psilocybin, a serotonergic psychedelic compound, has shown promise in treating both depression and substance use disorders. Its potential mechanisms include increased brain plasticity, enhanced connectivity between brain regions, improved emotional regulation, and the promotion of prosocial feelings. Earlier research has shown mixed results regarding its efficacy in reducing alcohol consumption, but more consistent findings in alleviating depressive symptoms. The authors proposed that psilocybin-assisted psychotherapy may help to improve both abstinence outcomes and mood in individuals recently detoxified from alcohol who present with depressive symptoms.
Methods
Study Design
Find this paper
https://doi.org/10.1111/add.70152
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Cite this paper (APA)
Luquiens, A., Belahda, D., Graux, C., Igounenc, N., Serrand, C., Rochefort, P., ... & Sergent, F. Psilocybin in alcohol use disorder and comorbid depressive symptoms: Results from a feasibility randomized clinical trial. Addiction.
Study details
Compounds studied
Placebo
Psilocybin
Topics studied
Depression
Alcohol Use Disorder
Addiction
Study characteristics
Original
Placebo-Controlled
Double-Blind
Randomized
Participants
30
Humans
Compound Details
The psychedelics given at which dose and how many times
Psilocybin 25 mg | 2xLinked Clinical Trial
Psilocybin in Alcohol Use Disorder With Comorbid Depression (PAD)This randomised, double-blind trial (n=30) is set to examine the feasibility, acceptability, and preliminary effectiveness of psilocybin therapy (25mg, 2x) in treating alcohol use disorder (AUD) with comorbid depression after withdrawal, alongside standard treatment.