Psilocybin-assisted Therapy for Comorbid Major Depressive Disorder and Alcohol Use Disorder

Official title

Psilocybin-assisted Therapy for Comorbid Major Depressive Disorder and Alcohol Use Disorder: A Pilot Randomized Clinical Trial

Overview

The goal of this clinical trial is to determine the safety and efficacy of psilocybin assisted Therapy (PAT) in individuals with comorbid Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD). The main question it aims to answer is: \- What is the feasibility and safety of administering PAT in adults with MDD-AUD by evaluating recruitment, retention, tolerability, and safety? Researchers will compare the psilocybin (25 mg) and placebo groups to see if there are any significant differences in frequency of dropouts or serious adverse events. Participants will: * be randomized to receive either psilocybin (25 mg) or placebo * visit the site (in-person and remotely) for a total of 14 times to complete study tasks * receive psilocybin-assisted therapy (PAT) at five various timepoints

Interventions

• Drug Psilocybin 25 mg
  Participants will orally consume Psilocybin (25 mg) with water.
• Drug Placebo
  Participants will orally consume placebo matching the intervention with water.

Primary outcome measures

• Adherence [Time frame: Week 2 (Visit 4)]
• Montgomery-Asberg Depression Rating Scale (MADRS) [Time frame: Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.]
• Hamilton Depression Rating Scale (HAMD-17) [Time frame: 4-week post dose; week 26.]
• Quick Inventory of Depressive Symptomatology - Self Report (QUIDS-SR) [Time frame: Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.]
• Alcohol Timeline Followback (TLFB) [Time frame: Baseline; week 2 (visit 3); 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.]
• Clinical Institute Withdrawal Assessment (CIWA) [Time frame: Baseline; week 2 (visit 3); week 2 (visit 4); 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.]
• Prediction of Alcohol Withdrawal Severity Scale (PAWSS) [Time frame: Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.]
• Penn Alcohol Craving Scale (PACS) [Time frame: Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.]
• Addiction Severity Index (ASI) [Time frame: Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post dose; 4-week post dose; week 10; week 14; week 18; week 22; week 26.]

Secondary outcome measures (12)

• 5 Dimensional Altered States of Consciousness (5-DASC) [Time frame: Week 2 (visit 4).]
• Psychological Insight Questionnaire (PIQ) [Time frame: Week 2 (visit 4).]
• Mystical Experience Questionnaire (MEQ) [Time frame: Week 2 (visit 4).]
• Challenging Experience Questionnaire (CEQ) [Time frame: Week 2 (visit 4).]
• General Anxiety Disorder-7th edition (GAD-7) [Time frame: Baseline; week 26.]
• State Trait Anxiety Index (STAI) [Time frame: Baseline; week 26.]
• World Health Organization Quality of Life Questionnaire Brief Version (WHOQOL-BREF) [Time frame: Baseline; week 26.]
• Big Five Inventory (BFI) [Time frame: Baseline; week 26.]
• Pittsburgh Sleep Quality Index (PSQI) [Time frame: Baseline; week 26.]
• Acceptance & Action Questionnaire II (AAQ-II) [Time frame: Baseline; 1-day post dose; 1-week post dose; 2-week post dose; 3-week post-dose; 4-week post-dose; week 10; week 14; week 18; week 22; week 26.]
• Stanford Expectations of Treatment Scale (SETS) [Time frame: Baseline]
• Working Alliance Inventory (WAI) [Time frame: Week 2 (visit 3); 1-day post dose; 1-week post dose.]

Eligibility criteria

Inclusion criteria

• Be between the ages of 18-65
• Must be deemed to have capacity to provide informed consent;
• Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent;
• Stated willingness to comply with all study procedures;
• Be deemed in health compatible with the study procedures according to study physician;
• Ability to take oral medication and be willing to adhere to the PAT regimen;
• Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation;
• Fulfil Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-5) criteria for a primary diagnosis of current single or recurrent episodes of MDD of at least moderate severity but without psychotic features and a comorbid AUD diagnosis (moderate or severe) using the SCID-5;
• A score of at least 14 on the Hamilton Depression Rating Scale for Depression (HAMD);
• Participants should not be interested in initiating standard pharmacotherapies for MDD or AUD. The need to start/resume standard pharmacotherapies will be reassessed at Week 6.
• Individuals who are willing to and tapered off current antidepressant or IMAOs, antipsychotic and anti-alcohol/anti-craving medications for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose physician confirms that it is safe for them to do so;
• Individuals who are willing to and have tapered off current inhibitors of 5'-diphospho-glucuronosyltransferase (UGT)1A9 and 1A10, aldehyde dehydrogenase inhibitors (ALDHs) and alcohol dehydrogenase inhibitors (ADHs) for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose physician confirms that it is safe for them to do so;
• Agreement to adhere to Lifestyle Considerations (section 4.5) throughout study duration.

Exclusion criteria

• Pregnant as assessed by a urine pregnancy test at Screening (V1) and Baseline (V2) or individual's that intend to become pregnant during the study or are breastfeeding;
• Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension (over 160/100 mmHG), low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment.
• Diagnosis of cirrhosis, AST or ALT elevations > 3x upper limit of normal; significant abnormal liver function that would preclude administration of psilocybin based on the judgement of the QI (assessed notably by bilirubin, albumin, alkaline phosphatase, GGT, and INR functions)
• Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; obsessive-compulsive disorder, psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history and the SCID-5 clinical interview;
• Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I or II disorder as determined by the family medical history form and discussions with the participant;
• Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) score > 9, or any other indication that the participant may experience medically complicated withdrawal from alcohol, such as a score of ≥4 in the Prediction of Alcohol Withdrawal Severity Scale.
• Use benzodiazepines (with the exception of use of up to 2mg of lorazepam equivalent per day for insomnia and anxiety if it is not taken within 12 hours before the psilocybin dose (Week 2).
• Have a DSM-5 diagnosis of substance use disorder (excluding alcohol, cannabis, tobacco and caffeine) within the preceding 6 months;
• Presence of baseline prolonged QTc (more than 0.45 seconds for males and 0.47 seconds for females) or Torsade de Pointes as measured by the ECG or a history of long QTc syndrome or related risk factors;
• Use of aldehyde dehydrogenase (ALDH) inhibitors and UDG modulators;
• Use of hallucinogens in the past 5 years; or total hallucinogen use ≥10 times)
• Current suicidality risk as indicated during the conduct of the Columbia Suicide Severity Rating Scale (C-SSRS) with concurrence after a study physician's evaluation if the response to C-SSRS questions 1 or 2 is "yes")
• Any other clinically significant physical illness including chronic infectious diseases or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.
• Participants that are responding to anti-alcohol or anti-craving medications

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• Centre for Addiction and Mental Health — Toronto

Identifiers

NCT: NCT07405606 · 071/2023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗