Psilocybin in Alcohol Use Disorder with Comorbid Depression
- Conditions
- Alcohol-Related DisordersDepressive DisorderAddiction
- Interventions
- Other: ElectroencephalogramOther: Blood samples for the analysis of immune and inflammatory profilesOther: stool samplesOther: MRI functional and cerebral
- Registration Number
- NCT06235411
- Lead Sponsor
- Centre Hospitalier Universitaire de Nīmes
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental group Psilocybin therapy - Control group Electroencephalogram - Control group stool samples - Experimental group Electroencephalogram - Experimental group Blood samples for the analysis of immune and inflammatory profiles - Experimental group stool samples - Experimental group MRI functional and cerebral - Control group Inactive Psilocybin therapy - Control group Blood samples for the analysis of immune and inflammatory profiles - Control group MRI functional and cerebral -
- Primary Outcome Measures
Name Time Method Feasibility of the intervention between groups After 2nd experimental session (Week 4) Number of patients who completed both sessions
- Secondary Outcome Measures
Name Time Method Feasibility of recruitment between groups 18 Months Number of patients screened per month/number of patients included per month.
Feasibility of retainment between groups 18 Months Average time (days) between screening and inclusion.
Feasibility of the trial between groups 18 Months Rate (%) of eligible patients who are included in the study.
Feasibility of randomization between groups 18 Months Rate (%) of patients included who had at least one treatment administration session
Feasibility of inclusion between groups 18 Months Rate (%) of assessment sessions that were completed.
Feasibility of therapeutic intervention between groups 18 Months Duration of assessment sessions (minutes).
Study acceptability between groups 18 Months Number of patients leaving the study prematurely for any reason.
Patient-reported reasons for abandoning the study between groups 18 Months Qualitative description of reasons cited by patients
Decrease in alcohol consumption between groups Week 12 Decrease in the percentage of days of heavy drinking days during previous 4 weeks versus baseline
Total alcohol consumption between groups Week 12 Total alcohol consumption during previous 4 weeks
Time before first drink Week 12 Days
Time to first day of heavy drinking Week 12 Days
Craving between groups Week 12 Craving Experience Questionnaire (CEQ) score; the CEQ evaluates intensity and frequency of craving from 11 intensity items in blocks a-c. Each item is rated between 0 ("Not at all") and 10 ("Extremely") for a total score between 0 and 110. The higher the score, the more intense the craving. A frequency of craving score is calculated by adding the values obtained from 11 items in blocks d-f. Each item is rated between 0 ("Never") and 10 ("Constantly") for a total craving frequency score between 0 and 110.
Quality of life between groups Week 12 Alcohol quality of life scale (AQoLS); the 34-item questionnaire measures the negative impact of the relationship with alcohol on quality of life through 7 dimensions: social relationships, activities, living conditions, etc. self-care, negative emotions, sleep and loss of control on a scale of 0 (not at all) to 3 (very much), for a total score of 102. There is no threshold value.
Depression between groups Week 12 Beck Depression Inventory (BDI II); a 21-item scale. Each item consists of 4 sentences corresponding to 4 degrees of increasing intensity of a symptom, rated from 0 to 3. Only the highest rating chosen for a given series is retained. The total score ranges from 0 to 39; with a higher score indicating greater intensity of depression.
Anxiety between groups Week 12 Beck Anxiety Inventory (BAI); a 21-question score of common symptoms of anxiety, such as numbness and tingling, and sweating. Responses are rated on a scale of 0 (not at all) to 3 (severely). Higher total scores indicate more severe anxiety symptoms. Thresholds are: 0-7: Minimal; 8-15: Light; 16-25: Moderate; 26-63: Severe.
Emotion regulation difficulties between groups Week 12 Difficulties in Emotion Regulation Scale (DERS); a 36-item questionnaire assessing multiple aspects of emotion dysregulation. The measure gives a total score and six subscores:1. Non-acceptance of emotional responses (NON-ACCEPTANCE); 2. Difficulties in adopting goal-oriented behavior (GOALS); 3. Difficulty controlling impulses (IMPULSE); 4. Lack of emotional awareness (AWARENESS); 5. Limited access to emotion regulation strategies (STRATEGIES); 6. Lack of emotional clarity (CLARITY), with a final score 0-100.
Rejection sensitivity between groups Week 12 Adult Rejection Sensitivity Questionnaire (A-RSQ); rejection sensitivity score calculated for 9 situations by multiplying the level of rejection concern by the level of rejection expectation. The total rejection sensitivity score is the average of the rejection sensitivity scores for the 9 situations.
Meaning in life between groups Week 12 Meaning in Life Questionnaire (MLQ); a 10-item score assessing two dimensions of meaning in life rated on a seven-point scale ranging from "absolutely true" to "absolutely false." The "Presence of Meaning" subscale measures the extent to which respondents believe their lives have meaning. The "Search for Meaning" subscale measures respondents' engagement and motivation in their efforts to find meaning or deepen their understanding of the meaning of their lives, with a final score of 5-35
Cognitive functioning between groups Second psilocybin session (Week 4) Conflict indices and task focus of the Visual Perspective Task (VPT); participants evaluate either the number of red dots that in a scene from their own point of view (self-perspective condition), or the number of dots that another no one present in the scene can see (self-perspective condition).
Role of cognitive function at baseline on change in the percentage of heavy drinking days in preceding 4 weeks Day 0 Montreal Cognitive Assessment (MoCA); measuring attention, concentration, executive functions, memory, language, visuoconstructive abilities, abstraction abilities, calculation and orientation. Score 0-30.
Role of Posttraumatic Stress Disorder at baseline on change in the percentage of heavy drinking days in preceding 4 weeks Day 0 Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), a 17-item scale assessing the intensity of 17 PTSD symptoms. Each question is rated between 1 and 5 depending on the intensity and frequency of symptoms over the previous month. Three scales: Intrusion (items 1 to 5); Avoidance (items 6 to 12); Hyperstimulation (items 13 to 17). Total score 17-85, with threshold of 44 for PTSD diagnosis.
Role of attachment at baseline on change in the percentage of heavy drinking days in preceding 4 weeks Day 0 RSQ (Relationship Scale Questionnaire); a 30-item questionnaire classifying into four categories of attachment (secure or autonomous, avoidant or detached, preoccupied or ambivalent, fearful or disorganized). Score 13-65.
Change in the percentage of heavy drinking days in preceding 4 weeks according to concomitant Selective serotonin reuptake inhibitors Week 6 Concomitant Selective serotonin reuptake inhibitors yes/no
Change in the percentage of heavy drinking days in preceding 4 weeks according to concomitant Selective serotonin reuptake inhibitorsof other treatments on change in the percentage of heavy drinking days in preceding 4 weeks Week 12 Concomitant Selective serotonin reuptake inhibitors yes/no
Role of the patient-reported quality of the hallucinogenic experience on change in the percentage of heavy drinking days in preceding 4 weeks End of 2nd psilocybin session (Week 4) 5D-ASC (5-Dimensional Altered States of Consciousness Questionnaire) dimension score after psilocybin sessions. A 94-item questionnaire (to be translated and retrotranslated) administered 5 to 6 hours after drug administration; visual analog scale of five main dimensions: "The absence of oceanic boundaries", "fear of ego dissolution", "restructuring of vision", "auditory alterations" and "reduction of vigilance".
Role of the quality of the hallucinogenic experience according to brain activity on change in the percentage of heavy drinking days in preceding 4 weeks Day after 2nd experimental session (Week 4) Electroencephalogram parameters: alpha coherence in the resting state
Change in the percentage of heavy drinking days in preceding 4 weeks according to the quality of the hallucinogenic experience Day after 2nd experimental session (Week 4) Hallucinogenic experience assessed through qualitative analysis of audio-recorded verbatim of the integration session.
immune profiles through the microbiota week 3 Evaluate participants' immune profiles in both groups through the microbiota before the first dose with circulating 16sDNA assay.
Evolution immune profiles through the microbiota week 3 Evaluate the evolution of the immune profiles of participants in both groups through the microbiota before the first dose with circulating 16sDNA assay.
Immune and inflammatory profiles using cerebral structural and functional MRI week 3 Evaluate the immune and inflammatory profiles in the 2 groups using cerebral structural and functional MRI 3 weeks after to the first psilocybin administration.
Evolution of Immune and inflammatory profiles using cerebral structural and functional MRI week 3 Evaluate the evolution of the immune and inflammatory profiles in the 2 groups using cerebral structural and functional MRI 3 weeks after to the first psilocybin administration.
Inflammatory profiles by measuring the cytokine TNF alpha in plasma week 3 Evaluate participants' inflammatory profiles in both groups through cytokine TNF alpha before the first dose. A tube of blood will be taken. The sample is transported to the laboratory at room temperature within 4 hours. Tubes are then centrifuged at 2000g for 10 min at room temperature, then aliquoted by 500µL into 1.5 mL Eppendorf LoBind Protein tubes for storage at -80°C prior to batch analysis.
analysis of intestinal microbiota : Number of species detected in the intestinal microbiota week 3 Patients will provide a stool sample, stored at -20°C and transported in an insulated bag to the hospital. The sample will be frozen at -80°C. The number of species detected in the intestinal microbiota will be recorded
analysis of intestinal microbiota : Distribution of species detected in the intestinal microbiota. week 3 Patients will provide a stool sample, stored at -20°C and transported in an insulated bag to the hospital. The sample will be frozen at -80°C. The distribution of the various bacterial species detected in the intestinal microbiota will be recorded
analysis of intestinal microbiota : Diversity of species detected in the intestinal microbiota. week 3 Patients will provide a stool sample, stored at -20°C and transported in an insulated bag to the hospital. The sample will be frozen at -80°C. The diversity index according to the number of species will be recorded
Inflammatory profiles by measuring the cytokine IL-1b in plasma week 3 Evaluate participants' inflammatory profiles in both groups through cytokine IL-1b before the first dose. A tube of blood will be taken. The sample is transported to the laboratory at room temperature within 4 hours.
Tubes are then centrifuged at 2000g for 10 min at room temperature, then aliquoted by 500µL into 1.5 mL Eppendorf LoBind Protein tubes for storage at -80°C prior to batch analysis.Inflammatory profiles by measuring the cytokine IL-6 in plasma week 3 Evaluate participants' inflammatory profiles in both groups through cytokine IL-6 before the first dose. A tube of blood will be taken. The sample is transported to the laboratory at room temperature within 4 hours.
Tubes are then centrifuged at 2000g for 10 min at room temperature, then aliquoted by 500µL into 1.5 mL Eppendorf LoBind Protein tubes for storage at -80°C prior to batch analysis.Inflammatory profiles by measuring the cytokine IL-8 in plasma week 3 Evaluate participants' inflammatory profiles in both groups through cytokine IL-8 before the first dose. A tube of blood will be taken. The sample is transported to the laboratory at room temperature within 4 hours.
Tubes are then centrifuged at 2000g for 10 min at room temperature, then aliquoted by 500µL into 1.5 mL Eppendorf LoBind Protein tubes for storage at -80°C prior to batch analysis.Inflammatory profiles by measuring the cytokine IL-10 in plasma week 3 Evaluate participants' inflammatory profiles in both groups through cytokine IL-10 before the first dose. A tube of blood will be taken. The sample is transported to the laboratory at room temperature within 4 hours.
Tubes are then centrifuged at 2000g for 10 min at room temperature, then aliquoted by 500µL into 1.5 mL Eppendorf LoBind Protein tubes for storage at -80°C prior to batch analysis.
Trial Locations
- Locations (1)
CHU
🇫🇷Nîmes, France