NCT07638553

Brief Summary

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
172

participants targeted

Target at P25-P50 for phase_3

Timeline
49mo left

Started Jun 2026

Typical duration for phase_3

Geographic Reach
1 country

8 active sites

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress1%
Jun 2026Jun 2030

Study Start

First participant enrolled

June 1, 2026

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

June 5, 2026

Completed
5 days until next milestone

First Posted

Study publicly available on registry

June 10, 2026

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2030

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2030

Last Updated

June 10, 2026

Status Verified

June 1, 2026

Enrollment Period

4 years

First QC Date

June 5, 2026

Last Update Submit

June 5, 2026

Conditions

Outcome Measures

Primary Outcomes (2)

  • Incidence of relapse between groups

    Relapse Yes/no, where relapse is defined as the 1st heavy drinking day, assessed using the Timeline Follow-Back (TLFB) method

    Month 6

  • Time to relapse between groups

    Days until relapse, where relapse is defined as the 1st heavy drinking day, assessed using the Timeline Follow-Back (TLFB) method

    Month 6

Secondary Outcomes (47)

  • Change in relapse rate between groups

    At weeks 3, 9, 15, 21, 27 compared to baseline

  • Change in rate of heavy drinking days between groups

    At weeks 3, 9, 15, 21, 27 compared to baseline

  • Change in total alcohol consumption between groups

    At weeks 3, 9, 15, 21, 27 compared to baseline

  • Change in number of drinking days between groups

    At weeks 3, 9, 15, 21, 27 compared to baseline

  • Change in craving between groups

    At weeks 3, 9, 15, 21, 27 compared to baseline

  • +42 more secondary outcomes

Study Arms (2)

High dose psilocybin

EXPERIMENTAL

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

Drug: Psilocybin (high dose)

Low-dose psilocybin

PLACEBO COMPARATOR

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

Drug: Psilocybin (low dose)

Interventions

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

High dose psilocybin

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

Low-dose psilocybin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Confirmed DSM-5 diagnosis of severe AUD.
  • Scale BDI-II ((Beck Depression Inventory) ≥14
  • 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

You may not qualify if:

  • 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
  • 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)
  • st degree family member with a diagnosed psychotic disorder
  • Severe cognitive impairment (clinician-judged)
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Centre Hospitalier de la Côte Basque

Bayonne, France

Location

CHU Besançon

Besançon, France

Location

CHU de Bordeaux

Bordeaux, France

Location

CHU Brest

Brest, France

Location

CH Le Vinatier

Bron, France

Location

CHU de Nantes

Nantes, France

Location

CHU de Nîmes

Nîmes, 30029, France

Location

CHU Saint-Etienne

Saint-Priest, France

Location

MeSH Terms

Conditions

Alcoholism

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Alcohol-Related DisordersSubstance-Related DisordersChemically-Induced DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Indole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingTryptaminesIndolizidinesIndolizines

Study Officials

  • Amandine Luquiens

    Centre Hospitalier Universitaire de Nīmes

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 5, 2026

First Posted

June 10, 2026

Study Start

June 1, 2026

Primary Completion (Estimated)

June 1, 2030

Study Completion (Estimated)

June 1, 2030

Last Updated

June 10, 2026

Record last verified: 2026-06

Locations