Clinical TrialParallelAlcohol Use Disorder (AUD)PsilocybinPsilocybinNot yet recruiting

Efficacy in Relapse Prevention: Psilocybin in Alcohol Use Disorder With Depressive Symptoms

This Phase III, randomised, triple-blind, parallel trial (n=172) will evaluate whether psilocybin-assisted psychotherapy can prevent relapse in adults with severe alcohol use disorder (AUD) and depressive symptoms after detoxification. The study will compare two administrations of high-dose psilocybin (25 mg) with two administrations of low-dose psilocybin (3 mg), given 3 weeks apart, with the main aim of reducing relapse over 6 months. Participants must have a confirmed DSM-5 diagnosis of severe AUD and a Beck Depression Inventory-II score of at least 14, with the last drink taken between day -60 and day -10 before inclusion. The primary outcomes are incidence of relapse and time to relapse at 6 months. Eligible adults of any sex will be enrolled at the Centre Hospitalier Universitaire de Nîmes, with study start planned for June 2026 and completion expected in June 2030.

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Target Enrollment
172 participants
Study Type
Phase III interventional
Design
Randomized, triple Blind

Detailed Description

Up to 40% of individuals with alcohol use disorder (AUD) experience depression, which increases the risk of early relapse. Depression can cause relapse to occur 3 times faster in individuals with AUD who experience depressive symptoms at discharge. No treatments have been approved for individuals with both AUD and depression. Psilocybin, a psychedelic, shows promising results in treating both depression and addiction. It may be particularly effective for preventing relapse in people with AUD who also have depressive symptoms after detoxification, offering quicker action than traditional antidepressants.

The Psilocybin Alcohol Depression (PAD) pilot study, launched in February 2024, has provided critical insights for avoiding methodological flaws and demonstrated that psilocybin-assisted psychotherapy (PAP) is both feasible and acceptable. Preliminary efficacy analyses were conducted: at 12 weeks, the 25 mg group showed significantly greater reductions in drinking days (p = 0.038) and craving frequency (p = 0.045). Relapse rates were 35% in the 25 mg group and 50% in the control group (HR = 0.52 \[0.16-1.65\]). In the ERPPAD trial, the study authors will compare high-dose PAP with low-dose PAP in preventing relapse in individuals with AUD and depressive symptoms. The hypothesis is that high-dose PAP will be more effective than low-dose in preventing relapse over 6 months.

Study Arms & Interventions

High dose psilocybin

experimental

2 administrations of high-dose psilocybin (25 mg) 3 weeks apart

Interventions

  • Psilocybin25 mg
    • 2 administrations 3 weeks apart• 2 doses total

Low-dose psilocybin

inactive

2 administrations of low-dose psilocybin (3 mg) 3 weeks apart

Interventions

  • Psilocybin3 mg
    • 2 administrations 3 weeks apart• 2 doses total

Participants

Ages
18 – ?
Sexes
Male & Female

Inclusion Criteria

  • Confirmed DSM-5 diagnosis of severe AUD.
  • Scale BDI-II ((Beck Depression Inventory) ≥14
  • The last drink must have been consumed between day(D) -60 and D -10 at the inclusion visit. The patient must have had at least 1 HDD during the last drinking period NB: The last drinking period before inclusion is defined by the last 4 weeks counted from the last drink.
  • The patient must have given their free and informed consent and signed the consent form
  • The patient must be a member or beneficiary of a health insurance plan

Exclusion Criteria

  • The subject is participating in an interventional study, a clinical trial, or a clinical investigation or is in a period of exclusion determined by a previous study
  • The subject refuses to sign the consent
  • It is impossible to give the subject informed information
  • The patient is under safeguard of justice or state guardianship
  • Patient unable to give informed consent.
  • Participants planning to donate sperm within three months of psilocybin administration
  • Positive pregnancy test at inclusion for participants of childbearing age.
  • Patient who is pregnant, breastfeeding, or wishing to become pregnant during participation in the study.
  • Any use of classical psychedelic in the last year
  • Other current substance use disorder (except tobacco)
  • Diagnosed schizophrenic or bipolar disorder
  • High emotional lability (clinician-judged)
  • On antipsychotics treatment that may interfere with psilocybin.
  • Need for monoamine oxidase inhibitor (MAOI) treatment, which may interfere with psilocybin.
  • Severe suicidal ideation (high risk on the Columbia scale)
  • 1st degree family member with a diagnosed psychotic disorder
  • Severe cognitive impairment (clinician-judged)
  • CIWA-AR \> 8
  • Medical conditions that would preclude safe participation in the trial, for example: seizure disorders; significant impairment of hepatic function; coronary artery disease; history of arrhythmia; Abnormal QT interval prolongation (QTc \> 470 ms for women and \>450 ms for men); heart failure; uncontrolled hypertension (greater than 165/95 mmHg at screening); history of stroke; severe asthma; hyperthyroidism; narrow-angle glaucoma; stenosing gastroduodenal ulcer; pyloroduodenal obstruction; symptomatic prostatic hypertrophy or bladder neck obstruction; uncontrolled type I or type II diabetes, or a history of ketoacidosis, hyperglycemic coma, or severe hypoglycemia with loss of consciousness.

Study Details

Study Team

Sponsors & Collaborators

Locations

Centre Hospitalier de la Côte Basque — Bayonne, France
CHU Besançon — Besançon, France
CHU de Bordeaux — Bordeaux, France
CHU Brest — Brest, France
CH Le Vinatier — Bron, France
CHU de Nantes — Nantes, France
CHU de Nîmes — Nîmes, France
CHU Saint-Etienne — Saint-Priest, France