Clinical TrialAlcohol Use Disorder (AUD)PsilocybinPsilocybinCompleted

Psilocybin in Alcohol Use Disorder With Comorbid Depression (PAD)

Randomised, quadruple-blind, parallel pilot trial (n=30) testing two oral administrations of psilocybin (25 mg) versus inactive 1 mg control, given 3 weeks apart, for AUD with comorbid depression alongside usual care.

Target Enrollment
30 participants
Study Type
Phase NA interventional
Design
Randomized, quadruple Blind

Detailed Description

This pilot parallel randomized trial will assess feasibility, acceptability, preliminary effectiveness and neural mechanisms of two psilocybin sessions (25 mg) versus inactive 1 mg control in recently withdrawn patients with severe alcohol use disorder and depressive symptoms.

Each treatment day includes preparation, a supervised dosing session (~6 hours) with music and accompaniment, and an integration session; outcomes include clinical measures of alcohol relapse and depression, EEG, blood immuno-inflammatory markers, stool microbiota and functional MRI.

Study Protocol

Preparation

2 sessions

Dosing

2 sessions
360 min each

Integration

2 sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Psilocybin 25 mg

experimental

Two 25 mg oral psilocybin sessions given 3 weeks apart with preparation and integration; plus EEG, blood, stool and fMRI assessments.

Interventions

  • Psilocybin25 mg
    via Oral• two sessions• 2 doses total

    Two administrations 3 weeks apart; patient accompanied during session (~6 hours); preparation day before and integration day after.

  • Compound
    via Other

    Electroencephalogram assessments at baseline, during first session, and post-integration.

  • Compound
    via Other

    Blood samples for immune/inflammatory profiling at day 0 and 3 weeks.

  • Compound
    via Other

    Stool samples for microbiota analysis at day 0 and 3 weeks.

  • Compound
    via Other

    Functional MRI at day 0 and 3 weeks.

Psilocybin 1 mg (control)

inactive

Two 1 mg oral psilocybin sessions (inactive control) given 3 weeks apart with same assessments and support.

Interventions

  • Psilocybin1 mg
    via Oral• two sessions• 2 doses total

    Inactive psilocybin control (1 mg) administered on same schedule; same accompaniment and assessments.

  • Compound
    via Other

    Electroencephalogram assessments at baseline, during first session, and post-integration.

  • Compound
    via Other

    Blood samples for immune/inflammatory profiling at day 0 and 3 weeks.

  • Compound
    via Other

    Stool samples for microbiota analysis at day 0 and 3 weeks.

  • Compound
    via Other

    Functional MRI at day 0 and 3 weeks.

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Patient with a confirmed DSM-5 diagnosis of severe alcohol use disorder.
  • BDI-II (Beck Depression Inventory) score ≥ 14.
  • Last alcohol consumption occurred between 60 and 14 days prior to inclusion; must have had at least one heavy drinking day in that period.
  • Free and informed consent.
  • Patient must be member or beneficiary of a health insurance plan.

Exclusion Criteria

  • Exclusion Criteria:
  • Participation in another interventional drug study or within exclusion period from a previous study.
  • Unable to express or receive informed consent; under legal guardianship.
  • Schizophrenic disorder or any history of psychotic disorder per clinician judgment.
  • Past or current manic or hypomanic episode.
  • Need for antipsychotic treatment that may interfere with psilocybin.
  • Need for MAOI treatment that may interfere with psilocybin.
  • Current scripted suicidal ideation judged 'high risk' on C-SSRS.
  • First-degree family member with psychotic disorder or bipolar I.
  • High risk of negative emotional/behavioural response (serious personality disorder, severe stressors, lack of social support).
  • Dementia or severe cognitive impairment.
  • CIWA-R score ≥ 8.
  • Medical conditions precluding safe participation (e.g., seizure disorder, significant liver impairment, coronary disease, arrhythmia, uncontrolled hypertension >165/95 mmHg, history of stroke, severe asthma, hyperthyroidism, narrow-angle glaucoma, peptic stenosis, prostate obstruction, uncontrolled diabetes with ketoacidosis).
  • History of hallucinogen use disorder, any psychedelic use in past year, or >25 lifetime uses.
  • Dependence on cocaine, psychostimulants, opioids or cannabis in last 12 months.
  • Current non-medical use of cocaine, psychostimulants or opioids in past 30 days.
  • Serious ECG abnormalities (e.g., ischemia, MI, QTc prolongation >0.45s men, >0.47s women).
  • Hypersensitivity to active ingredient or excipients.
  • No access to email or insufficient French language comprehension.
  • Pregnant or breastfeeding, or planning pregnancy.

Study Details

Locations

CHU — Nîmes, Nîmes, France

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