Psilocybin in Alcohol Use Disorder With Comorbid Depression

NCT06235411 | Completed

• 1 other identifier: IRESP/2022/AL-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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a control condition (1 mg psilocybin), in addition to the usual treatment, will be acceptable and feasible in recently withdrawn individuals suffering from AUD and depressive symptoms, between 14 and 60 days after their last alcohol consumption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

Keywords

Psilocybin; Psychedelic assisted therapy

Outcome Measures

Primary Outcomes (1)

• Feasibility of the intervention between groups

  Number of patients who completed both sessions

  After 2nd experimental session (Week 4)

Secondary Outcomes (76)

• Feasibility of recruitment between groups

  18 Months

• Feasibility of retainment between groups

  18 Months

• Feasibility of the trial between groups

  18 Months

• Feasibility of randomization between groups

  18 Months

• Feasibility of inclusion between groups

  18 Months

Study Arms (2)

Experimental group

EXPERIMENTAL

Drug: Psilocybin therapy; Other: Electroencephalogram; Other: Blood samples for the analysis of immune and inflammatory profiles; Other: stool samples; Other: MRI functional and cerebral

Control group

PLACEBO COMPARATOR

Drug: Inactive Psilocybin therapy; Other: Electroencephalogram; Other: Blood samples for the analysis of immune and inflammatory profiles; Other: stool samples; Other: MRI functional and cerebral

Interventions

Psilocybin therapy 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).

Experimental group

Inactive Psilocybin therapy 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).

Control group

Electroencephalogram OTHER

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

Control group; Experimental group

Blood samples for the analysis of immune and inflammatory profiles OTHER

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

Control group; Experimental group

stool samples 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.

Control group; Experimental group

MRI functional and cerebral OTHER

MRI functional and cerebral at day 0 and 3 weeks

Control group; Experimental group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with a confirmed DSM-5 diagnosis of severe alcohol use disorder.
• BDI II (Beck Depression Inventory) score ≥ 14.
• Patient with free and informed consent.
• The patient must be a member or beneficiary of a health insurance plan

You may not qualify if:

• The subject is participating in an interventional study involving a drug or in a clinical trial according to the REC.
• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (1)

CHU

Nîmes, Nîmes, 30029, France

Location

MeSH Terms

Conditions

Alcohol-Related Disorders; Depressive Disorder; Behavior, Addictive

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Mood Disorders; Compulsive Behavior; Impulsive Behavior; Behavior

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Amandine Luquiens

  CHU de Nimes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: January 31, 2024
• Study Start: February 5, 2024
• Primary Completion: November 19, 2024
• Study Completion: January 9, 2025
• Last Updated: March 19, 2025

Record last verified: 2025-03

Locations

FR (1)