Psilocybin in Alcohol Use Disorder With Comorbid Depression

NCT ID: NCT06235411

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-05
• Study Completion Date: 2025-01-09

Brief Summary

Up to 40% of people with alcohol use disorder (AUD) experience depression. Depression is a risk factor for early relapse of AUD after withdrawal in a controlled environment. Promising data suggest the effectiveness of psilocybin, a psychedelic-type treatment, in depression and AUD. Following the acute effects of the psychedelic experience, which lasts approximately 6 hours, psilocybin action appears to be beneficial for preventing alcohol relapse in recently weaned people suffering from comorbid depression. Whilst the public perception of psilocybin therapy is poorly documented in France, the rapid changes in the legal status of psilocybin elsewhere, the positive media coverage of recent trials in depression, and the recent designation as an "innovative therapy" by the FDA could lead to the refusal of randomization of eligible participants. It is therefore essential to evaluate the feasibility and acceptability of psilocybin treatment and blinded randomized design in our clinical population of hospitalized patients with AUD and depressive symptoms. Recent data suggest that the effect size of psilocybin is much higher than other currently available treatments. However, this paradigm shift must be confirmed in our cohort of people with AUD and depressive symptoms, and in the context of treatment in addition to usual care, by an estimation of the expected effect size based on real data. This will allow the sample size to be accurately calculated for a large-scale randomized clinical trial. Finally, the potential mechanisms of action of psilocybin to prevent relapse in AUD with comorbid depression after withdrawal need to be documented. The objective of this pilot study is to evaluate the feasibility, acceptability, neural mechanisms and preliminary results of the effectiveness of psilocybin in the treatment of AUD and depressive symptoms after withdrawal, in addition to usual treatment. The study authors hypothesize that two oral administrations of 25 mg psilocybin at three-week intervals versus a control condition (1 mg psilocybin), in addition to the usual treatment, will be acceptable and feasible in recently withdrawn individuals suffering from AUD and depressive symptoms, between 14 and 60 days after their last alcohol consumption

Conditions

Alcohol-Related Disorders; Depressive Disorder; Addiction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Experimental group

Group Type: EXPERIMENTAL

Psilocybin therapy

Intervention Type: DRUG

Two administrations of psilocybin given 3 weeks apart. The treatment day will begin around 9 a.m. with a brief interview. Patients will be invited to relax and music will be played through speakers and headphones.

One 25 mg capsule of Psilocybin will be given approximately 30 minutes to 1.5 hours later.

The patient is accompanied throughout the session (minimum 6 hours depending on the effects felt). The patient will benefit from a preparation session the day before dosing, and an integration session the day after. Intensive relapse prevention program will be dispensed between the 2 dosing sessions (treatment as usual).

Electroencephalogram

Intervention Type: OTHER

• Rest EEG prior to first treatment administration
• EEG during first treatment administration
• Rest EEG during integration session after second treatment administration

Blood samples for the analysis of immune and inflammatory profiles

Intervention Type: OTHER

Three 7ml EDTA tubes will be taken in the morning on an empty stomach at day 0 and at 3 weeks.

stool samples

Intervention Type: OTHER

Stool sampling at day 0 and 3 weeks Analysis of intestinal microbiota is carried out on a stool sample, which is stored at -20°C for a maximum of 24 hours. The sample is then transferred cold to the CRB of the Nîmes University Hospital, where it is stored at -80°C until the microbiology laboratory can perform a group analysis.

MRI functional and cerebral

Intervention Type: OTHER

MRI functional and cerebral at day 0 and 3 weeks

Control group

Group Type: PLACEBO_COMPARATOR

Inactive Psilocybin therapy

Intervention Type: DRUG

Two administrations of psilocybin given 3 weeks apart. The treatment day will begin around 9 a.m. with a brief interview. Patients will be invited to relax and music will be played through speakers and headphones.

One 1 mg capsule of Psilocybin will be given approximately 30 minutes to 1.5 hours later.

The patient is accompanied throughout the session (minimum 6 hours depending on the effects felt). The patient will benefit from a preparation session the day before dosing, and an integration session the day after. Intensive relapse prevention program will be dispensed between the 2 dosing sessions (treatment as usual).

Electroencephalogram

Intervention Type: OTHER

• Rest EEG prior to first treatment administration
• EEG during first treatment administration
• Rest EEG during integration session after second treatment administration

Blood samples for the analysis of immune and inflammatory profiles

Intervention Type: OTHER

Three 7ml EDTA tubes will be taken in the morning on an empty stomach at day 0 and at 3 weeks.

stool samples

Intervention Type: OTHER

Stool sampling at day 0 and 3 weeks Analysis of intestinal microbiota is carried out on a stool sample, which is stored at -20°C for a maximum of 24 hours. The sample is then transferred cold to the CRB of the Nîmes University Hospital, where it is stored at -80°C until the microbiology laboratory can perform a group analysis.

MRI functional and cerebral

Intervention Type: OTHER

MRI functional and cerebral at day 0 and 3 weeks

Interventions

Psilocybin therapy

Two administrations of psilocybin given 3 weeks apart. The treatment day will begin around 9 a.m. with a brief interview. Patients will be invited to relax and music will be played through speakers and headphones.

One 25 mg capsule of Psilocybin will be given approximately 30 minutes to 1.5 hours later.

The patient is accompanied throughout the session (minimum 6 hours depending on the effects felt). The patient will benefit from a preparation session the day before dosing, and an integration session the day after. Intensive relapse prevention program will be dispensed between the 2 dosing sessions (treatment as usual).

Intervention Type: DRUG

Inactive Psilocybin therapy

Two administrations of psilocybin given 3 weeks apart. The treatment day will begin around 9 a.m. with a brief interview. Patients will be invited to relax and music will be played through speakers and headphones.

One 1 mg capsule of Psilocybin will be given approximately 30 minutes to 1.5 hours later.

The patient is accompanied throughout the session (minimum 6 hours depending on the effects felt). The patient will benefit from a preparation session the day before dosing, and an integration session the day after. Intensive relapse prevention program will be dispensed between the 2 dosing sessions (treatment as usual).

Intervention Type: DRUG

Electroencephalogram

• Rest EEG prior to first treatment administration
• EEG during first treatment administration
• Rest EEG during integration session after second treatment administration

Intervention Type: OTHER

Blood samples for the analysis of immune and inflammatory profiles

Three 7ml EDTA tubes will be taken in the morning on an empty stomach at day 0 and at 3 weeks.

Intervention Type: OTHER

stool samples

Stool sampling at day 0 and 3 weeks Analysis of intestinal microbiota is carried out on a stool sample, which is stored at -20°C for a maximum of 24 hours. The sample is then transferred cold to the CRB of the Nîmes University Hospital, where it is stored at -80°C until the microbiology laboratory can perform a group analysis.

Intervention Type: OTHER

MRI functional and cerebral

MRI functional and cerebral at day 0 and 3 weeks

Intervention Type: OTHER

Eligibility 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 must have occurred between 60 and 14 days prior to study inclusion. The patient must have had at least one heavy drinking day during the last period of alcohol consumption.

NB: The last period of alcohol consumption prior to inclusion is defined as the last 4 weeks counted from the last drink.

• Patient with free and informed consent.
• The patient must be a member or beneficiary of a health insurance plan

Exclusion Criteria

• The subject is participating in an interventional study involving a drug or in a clinical trial according to the REC.
• The subject is in a period of exclusion determined by a previous study
• The subject unable to express consent
• It is impossible to give the subject informed information
• The patient is under safeguard of justice or state guardianship
• Schizophrenic disorder, or any history of psychotic disorder according to the clinician's judgment.
• Past or current manic or hypomanic episode.
• Need for antipsychotic treatment that may interfere with psilocybin.
• Need for treatment with monoamine oxidase inhibitors (MAOIs) which may interfere with psilocybin.
• Current scripted suicidal ideation (according to clinician judgment) corresponding to a "high risk" score on the Columbia-Suicide Severity Rating Scale (C-SSRS).
• First-degree family member diagnosed with psychotic disorder or bipolar disorder type 1.
• High risk of negative emotional or behavioral response based on the investigator's clinical judgment (e.g., signs of serious personality disorders, antisocial behavior, severe current stressors, lack of meaningful social support)
• Patient with dementia or severe cognitive impairment (as judged by the clinician).
• CIWA-R score ≥ 8.
• Medical conditions that would prevent safe participation in the trial; for example: seizure disorders, significant impairment of liver function, coronary heart disease, history of arrhythmia, heart failure, uncontrolled hypertension (greater than 165/95 mmHg at screening), history of stroke, severe asthma, hyperthyroidism, narrow-angle glaucoma, stenotic peptic ulcer, pyloroduodenal obstruction, symptomatic enlarged prostate or bladder neck obstruction), Uncontrolled type I or type II diabetes or history of ketoacidosis, hyperglycemic coma or severe hypoglycemia with loss of conscience
• History of hallucinogen use disorder, any use in the past year or >25 lifetime uses.
• Dependence on cocaine, psychostimulants, opioids or cannabis (last 12 months).
• Current non-medical use of cocaine, psychostimulants or opioids (past 30 days).
• Serious ECG abnormalities (e.g., signs of ischemia, myocardial infarction, QTc prolongation (QTc > 0.45 seconds for men, QTc > 0.47 seconds for women).
• Hypersensitivity to the active ingredient or excipients
• No access to email.
• Insufficient understanding of French to complete the questionnaires.
• Patient for whom it is impossible to provide informed information.
• Pregnant or breastfeeding patient.
• Patient planning a pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Nīmes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amandine Luquiens

Role: PRINCIPAL_INVESTIGATOR

CHU de Nimes

Locations

CHU

Nîmes, Nîmes, France

Countries

France

Other Identifiers

IRESP/2022/AL-01

Identifier Type: -

Identifier Source: org_study_id