Psilocybin in Alcohol Use Disorder With Comorbid Depression

Depressive Disorder Clinical Trial

— PAD  

Official title:

Psilocybin in Alcohol Use Disorder With Comorbid Depression

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06235411
• Other study ID #: IRESP/2022/AL-01
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2024
• Est. completion date: July 2025

Study information

• Verified date: January 2024
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: Amandine Luquiens
• Phone: 04.66.68.69.98
• Email: amandine.luquiens[@]chu-nimes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Addiction
• Alcohol-Related Disorders
• Alcoholism
• Depressive Disorder

Intervention

Drug:
• 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).
• 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).

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

Locations

Country	Name	City	State
France	CHU	Nîmes

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of the intervention between groups	Number of patients who completed both sessions	After 2nd experimental session (Week 4)
Secondary	Feasibility of recruitment between groups	Number of patients screened per month/number of patients included per month.	18 Months
Secondary	Feasibility of retainment between groups	Average time (days) between screening and inclusion.	18 Months
Secondary	Feasibility of the trial between groups	Rate (%) of eligible patients who are included in the study.	18 Months
Secondary	Feasibility of randomization between groups	Rate (%) of patients included who had at least one treatment administration session	18 Months
Secondary	Feasibility of inclusion between groups	Rate (%) of assessment sessions that were completed.	18 Months
Secondary	Feasibility of therapeutic intervention between groups	Duration of assessment sessions (minutes).	18 Months
Secondary	Study acceptability between groups	Number of patients leaving the study prematurely for any reason.	18 Months
Secondary	Patient-reported reasons for abandoning the study between groups	Qualitative description of reasons cited by patients	18 Months
Secondary	Decrease in alcohol consumption between groups	Decrease in the percentage of days of heavy drinking days during previous 4 weeks versus baseline	Day 0
Secondary	Decrease in alcohol consumption between groups	Decrease in the percentage of days of heavy drinking days during previous 4 weeks versus baseline	Week 6 (or discharge if it takes place later)
Secondary	Decrease in alcohol consumption between groups	Decrease in the percentage of days of heavy drinking days during previous 4 weeks versus baseline	Week 12
Secondary	Total alcohol consumption between groups	Total alcohol consumption during previous 4 weeks	Day 0
Secondary	Total alcohol consumption between groups	Total alcohol consumption during previous 4 weeks	Week 6 (or discharge if it takes place later)
Secondary	Total alcohol consumption between groups	Total alcohol consumption during previous 4 weeks	Week 12
Secondary	Time before first drink	Days	Day 0
Secondary	Time before first drink	Days	Week 6 (or discharge if it takes place later)
Secondary	Time before first drink	Days	Week 12
Secondary	Time to first day of heavy drinking	Days	Day 0
Secondary	Time to first day of heavy drinking	Days	Week 6 (or discharge if it takes place later)
Secondary	Time to first day of heavy drinking	Days	Week 12
Secondary	Craving between groups	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.	Day 0
Secondary	Craving between groups	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.	Week 12
Secondary	Quality of life between groups	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.	Day 0
Secondary	Quality of life between groups	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.	Week 12
Secondary	Depression between groups	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.	Day 0
Secondary	Depression between groups	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.	Week 12
Secondary	Anxiety between groups	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.	Day 0
Secondary	Anxiety between groups	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.	Week 12
Secondary	Emotion regulation difficulties between groups	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.	Day 0
Secondary	Emotion regulation difficulties between groups	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.	Week 12
Secondary	Rejection sensitivity between groups	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.	Day 0
Secondary	Rejection sensitivity between groups	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.	Week 12
Secondary	Meaning in life between groups	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	Day 0
Secondary	Meaning in life between groups	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	Week 3
Secondary	Meaning in life between groups	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	Week 6
Secondary	Meaning in life between groups	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	Week 12
Secondary	Cognitive functioning between groups	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).	Day 0
Secondary	Cognitive functioning between groups	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).	Second psilocybin session (Week 4)
Secondary	Role of cognitive function at baseline on change in the percentage of heavy drinking days in preceding 4 weeks	Montreal Cognitive Assessment (MoCA); measuring attention, concentration, executive functions, memory, language, visuoconstructive abilities, abstraction abilities, calculation and orientation. Score 0-30.	Day 0
Secondary	Role of Posttraumatic Stress Disorder at baseline on change in the percentage of heavy drinking days in preceding 4 weeks	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.	Day 0
Secondary	Role of attachment at baseline on change in the percentage of heavy drinking days in preceding 4 weeks	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.	Day 0
Secondary	Change in the percentage of heavy drinking days in preceding 4 weeks according to concomitant Selective serotonin reuptake inhibitors	Concomitant Selective serotonin reuptake inhibitors yes/no	Day 0
Secondary	Change in the percentage of heavy drinking days in preceding 4 weeks according to concomitant Selective serotonin reuptake inhibitors	Concomitant Selective serotonin reuptake inhibitors yes/no	Week 3
Secondary	Change in the percentage of heavy drinking days in preceding 4 weeks according to concomitant Selective serotonin reuptake inhibitors	Concomitant Selective serotonin reuptake inhibitors yes/no	Week 6
Secondary	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	Concomitant Selective serotonin reuptake inhibitors yes/no	Week 12
Secondary	Role of the patient-reported quality of the hallucinogenic experience on change in the percentage of heavy drinking days in preceding 4 weeks	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".	End of 1st psilocybin session (Week 1)
Secondary	Role of the patient-reported quality of the hallucinogenic experience on change in the percentage of heavy drinking days in preceding 4 weeks	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".	End of 2nd psilocybin session (Week 4)
Secondary	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	Electroencephalogram parameters: alpha coherence in the resting state	Before 1st experimental session (Week 1)
Secondary	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	Electroencephalogram parameters: alpha coherence in the resting state	During the 1st experimental session (Week 1)
Secondary	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	Electroencephalogram parameters: alpha coherence in the resting state	Day after 2nd experimental session (Week 4)
Secondary	Change in the percentage of heavy drinking days in preceding 4 weeks according to the quality of the hallucinogenic experience	Hallucinogenic experience assessed through qualitative analysis of audio-recorded verbatim of the integration session.	Day after 1st experimental session (Week 1)
Secondary	Change in the percentage of heavy drinking days in preceding 4 weeks according to the quality of the hallucinogenic experience	Hallucinogenic experience assessed through qualitative analysis of audio-recorded verbatim of the integration session.	Day after 2nd experimental session (Week 4)