DRY EXTRACT FROM PSILOCYBE CUBENSIS (15-25:1), EXTRACTION SOLVENT: METHANOL for Severe Alcohol Use Disorder

Inclusion criteria

• {"criterion_text":"- Male or female patients between 21 and 70 years old, with a minimum BMI of 17.5 kg/m2 who want to stop or decrease their drinking;\n- Agree to have all PATh sessions (preparation, administration, integration) and semi-structured interviews recorded\n- Have a diagnosis of Severe Alcohol Use Disorder (sAUD), according to the DSM-V (6 criteria or more), ascertained using the Mini International Neuropsychiatric Interview (M.I.N.I 7.0.2).\n- Are not currently receiving any pharmacological treatment for sAUD and are willing to engage in all study requirements (including attending all study visits, preparatory sessions, integration sessions, follow-up sessions, and completing all study evaluations).\n- Female participants of childbearing potential must have a negative serum pregnancy test at admission (day 1 +/-2) and a negative urine pregnancy test the day before psilocybin administration (day 19 +/-2).\n- Women of childbearing potential must be using an effective, established method of contraception from inclusion until four weeks post-hospital discharge (5 weeks post-psilocybin administration). The following methods of contraception, if used properly and used for the duration of the study, are considered reliable: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: - oral, - intravaginal, - transdermal; progestogenonly hormonal contraception associated with inhibition of ovulation: - oral, - injectable, - implantable; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner (provided that partner is the sole sexual partner of the woman of child-bearing potential trial participant and that the vasectomised partner has received medical assessment of the surgical success; sexual abstinence (only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject). Note: female participants who are permanently sterilized (eg hysterectomy and/or bilateral salpingectomy) or post-menopausal (at least 48 consecutive weeks without menstruation) are not considered as being of childbearing potential\n- Men with a woman of childbearing potential partner should use a condom from inclusion until four weeks post-hospital discharge (5 weeks post-psilocybin administration).\n- Good physical health with no unstable medical conditions, as determined by medical history, physical examination, routine blood labs, electrocardiogram, urine analysis, and urine toxicology.\n- Willing to refrain from consuming psychoactive substances after enrolling in the study and during follow-up\n- Ability to provide voluntary written informed consent after receiving written information about the study protocol\n- Undergoing a 4-week alcohol detoxification program at the Brugmann University Hospital\n- Remaining abstinent from alcohol during the detoxification program (abstinence will be monitored using a breathalyzer during unannounced checks)\n- Normal level of language comprehension (French)\n- Affiliation to the Belgian social security system."}

Exclusion criteria

• {"criterion_text":"- - Allergy, hypersensitivity, or other adverse reaction to previous use of psilocybin or other hallucinogens\n- Current active ASD/PTSD\n- Lifetime history of schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, unspecified), other psychotic disorders or bipolar spectrum disorders (Type I, II, unspecified).\n- Lifetime history of major depressive episode with psychotic features.\n- Significant risk of suicide according to clinician assessment.\n- Family history of schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, unspecified), other psychotic disorders or bipolar\n- Type I in first- or second-degree relatives. Other substance use disorder (except for caffeine or nicotine) according to DSM V criteria in the two months preceding inclusion to the study.\n- Need to take medication with significant potential to interact with classical psychedelics (e.g., antidepressants except SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs), antipsychotics, psychostimulants, treatments for alcohol addiction as naltrexone or acamprosate or baclofen, opioid agonist treatment as buprenorphine or methadone, lithium, anticonvulsants, other dopaminergic or serotonergic agents)\n- History of hallucinogen use disorder, any use in the past 1 year, or >25 lifetime uses.\n- Pregnancy and breastfeeding, at screening visit and till dosing day.\n- Known or suspected non-compliance\n- Uncorrected hypertension\n- Previous enrolment into the current study\n- Enrolment of the investigator, his/her family members, employees and other dependent persons.\n- Patient subject to a legal protection measure (guardianship, curatorship or safeguard of justice), patient unable to express consent and not subject to a protection measure\n- Patients with language barrier (unable to follow the protocol or respond to clinical assessments).\n- Cardiovascular diseases, hepatic diseases, gastroenterological diseases, hematologic diseases, renal diseases, endocrine diseases, metabolic diseases, inflammatory diseases, neurological diseases or any other somatic condition that, in the opinion of the medical investigator (necessarily an MD), would pose a risk to the participant's participation in the study.\n- Other somatic condition that, in the opinion of the investigator, would pose a risk to the participant's participation in the study\n- Decompensated hepatic cirrhosis, defined by Child B or C score\n- Serious abnormalities of complete blood count or chemistries, biological abnormalities including TP < 50%, albumin < 35 g/L, total bilirubin > 35 μmol/L, leading to a Child B or C score\n- Abnormal electrocardiogram\n- Cognitive impairment (Folstein Mini Mental State Exam (Folstein et al., 1975) score < 26).\n- Alcohol withdrawal complication(s), head injury or stroke within the last 6 months"}

Primary endpoints

• {"endpoint_text":"- Primary clinical outcome: alcohol consumption in terms of changes in the percentage of heavy drinking days from baseline to four weeks posthospital discharge, measured with the timeline follow-back method. Self-reported alcohol consumption data will be corroborated with the surrogate outcome blood phosphatidyl-ethanol concentration at four weeks post-hospital discharge. Primary feasibility and safety outcome: recruitment rate and retention (feasibility), adverse events (safety).","definition_or_measurement_approach":"Alcohol consumption: changes in % heavy drinking days from baseline to 4 weeks post-hospital discharge measured with the timeline follow-back method; corroborated with blood phosphatidyl-ethanol concentration at 4 weeks. Feasibility: recruitment rate and retention. Safety: adverse events."}

Secondary endpoints

• {"endpoint_text":"- Alcohol consumption: - changes in terms of percent heavy drinking days and drinks per days, from baseline to six months post-hospital discharge. Percent days abstinent, from hospital discharge to six months post-hospital discharge, measured with the timeline follow-back method","definition_or_measurement_approach":"Measured with the timeline follow-back method assessing percent heavy drinking days, drinks per day and percent days abstinent from discharge to 6 months."}
• {"endpoint_text":"- (Neuro)cognitive measures: - EEG-derived auditory long-term potentiation (neuroplasticity). - EEG-derived-alcohol cue reactivity and inhibition. - Brief Evaluation of Alcohol-Related Neuropsychological Impairments","definition_or_measurement_approach":"EEG-derived measures for auditory long-term potentiation and alcohol cue reactivity/inhibition; brief neuropsychological assessment (Brief Evaluation of Alcohol-Related Neuropsychological Impairments)."}
• {"endpoint_text":"- Acute Psychedelic Effects: - The Revised Mystical Experience Questionnaire-30 items, - The Acceptance/Avoidance-Promoting Experiences Questionnaire, - The Helioscope Questionnaire, - A 20-item Monitor Rating Scale.","definition_or_measurement_approach":"Patient-reported scales/questionnaires (RMEQ-30, Acceptance/Avoidance-Promoting Experiences Questionnaire, Helioscope Questionnaire, 20-item Monitor Rating Scale) administered to assess acute psychedelic effects."}
• {"endpoint_text":"- Psychological Processes: - The Acceptance and Action Questionnaire II (psychological flexibility), - The Multidimensional Assessment of Interoceptive Awareness Scale (interoception), - The Watts Connectedness Scale (connectedness).","definition_or_measurement_approach":"Validated questionnaires assessing psychological flexibility, interoception, and connectedness."}
• {"endpoint_text":"- Alcohol-related parameters: - Penn Alcohol Craving Scale (craving), - Alcohol Abstinence Self-Efficacy Scale (abstinence self-efficacy), - Readiness rulers (motivation to change drinking behaviour).","definition_or_measurement_approach":"Standardized questionnaires for craving, self-efficacy, and readiness to change."}
• {"endpoint_text":"- Additional clinical outcomes: - Beck Depression Inventory (depressive symptoms), - State-Trait Anxiety Inventory (anxiety symptoms), - Substance Use Recovery Evaluator (substance use recovery), - International Trauma Questionnaire (Subsyndromal trauma symptoms).","definition_or_measurement_approach":"Standard clinical questionnaires for depression, anxiety, recovery and trauma-related symptoms."}
• {"endpoint_text":"- Expectancy and blinding: - Blinding efficacy (belief of treatment arm allocation, therapist and participant), - Stanford Expectations of Treatment Scale (expectancy).","definition_or_measurement_approach":"Assess blinding efficacy (participant/therapist beliefs) and expectancy via Stanford Expectations of Treatment Scale."}
• {"endpoint_text":"- Therapeutic alliance: - Working Alliance Inventory-Short Revised.","definition_or_measurement_approach":"Working Alliance Inventory-Short Revised questionnaire to assess therapeutic alliance."}
• {"endpoint_text":"- Treatment Satisfaction: - Visual Analog Scale.","definition_or_measurement_approach":"Visual Analog Scale for treatment satisfaction."}
• {"endpoint_text":"- Qualitative outcomes: - Three semi-structured interviews to explore the evolution of participants' expectations, representations and motivation regarding PATh, as well as characterize participant's experience of PATh within the context of an inpatient detoxification program, and processes of changes in terms of changes in attitudes towards drinking, the self, others and the world; and resulting behavioral changes","definition_or_measurement_approach":"Three semi-structured qualitative interviews exploring expectations, experiences, motivations, and processes of change; qualitative analysis planned."}

Belgium

Earliest CTIS Part Ii Submission Date

12-09-2024

Latest Decision Or Authorization Date

29-04-2025

Processing Time Days

229

Number Of Sites

1

Number Of Participants

62

Primary sponsor

Full Name

Association Hospitaliere De Bruxelles Et De Schaerbeek Centre Hospitalier Universitaire Brugmann

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium

Third parties

• {"country":"","full_name":"Fondation Brugmann","duties_or_roles":"Monetary support","organisation_type":""}