Clinical trial NCT06444243: Psilocybin-assisted Therapy for Alcohol Use Disorder
Official title: A Multi-centre, Double-blinded, Placebo-controlled, Randomised, Phase II Clinical Trial for Psilocybin-assisted Therapy for Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Alcohol Use Disorder
Alcohol Dependence
Depression
Anxiety
Keywords: Psilocybin-assisted therapy
Randomised-Controlled Trial
Psilocybin
Psychedelic-Assisted Therapy
Alcohol Use Disorder Therapy
Lead sponsor: University of Sydney
Sponsor class: OTHER
Collaborators: name: Woke Pharmaceuticals
First posted: 2024-06-05
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-centre, Double-blinded, Randomised, Phase II Clinical Trial for Psilocybin-assisted Therapy for Alcohol Use Disorder
Primary purpose: OTHER

Brief summary: To explore the effectiveness of psilocybin-assisted therapy on reducing alcohol consumption in a double-blind, randomised, phase II clinical trial.

Detailed description: New strategies for treating Alcohol Use Disorder (AUD) are urgently needed. Recent evidence has shown promising results for psychedelic-assisted therapies, particularly psilocybin, which has demonstrated efficacy in reducing alcohol consumption and improving psychological well-being. This study aims to evaluate the clinical efficacy and tolerability of psilocybin-assisted therapy compared to a control (niacin) in reducing heavy drinking days (HDD) per week among individuals with AUD.

Primary Objective

To conduct a double-blind, randomised controlled trial with 90 participants diagnosed with Alcohol Use Disorder (AUD). The primary aim is to compare the efficacy of psilocybin-assisted therapy (two sessions of psilocybin, 25 mg per dosing session) versus control (niacin 250mg) and therapy in reducing alcohol consumption, specifically measuring the number of heavy drinking days (HDD) per week.

Secondary Objectives

To compare the efficacy of psilocybin-assisted therapy versus control in improving the characteristics of AUD and addressing common comorbidities associated with AUD, including depression and anxiety.

Study Design

The trial will employ a double-blind, randomised, controlled design. A sample of 90 individuals with AUD will undergo 14 weeks of treatment, which includes 12 therapy sessions and 2 dosing sessions with either psilocybin (25 mg) or control (niacin 250mg). Participants will be assessed for changes in alcohol consumption patterns and improvements in symptoms of depression and anxiety.

Eligibility criteria: Inclusion Criteria:

1. Moderate to severe AUD according to the DSM-5 criteria
2. A desire to reduce or stop drinking
3. Consumed at least 21 standard drinks per week or ≥2 HDD (≥5 standard drinks/day for men; ≥4 for women) in the past week prior to screening
4. Aged ≥18 years old
5. Adequate cognition and English language skills to give valid consent and complete research interviews and assessments (MoCA ≥26)
6. Received prior treatment for AUD (not including study interventions)
7. Stable housing within reasonable distance to a clinical site for the duration of the study
8. Able to identify a significant other (such as a family/friend/partner) who could accompany them from clinic/provide transport and/or be contacted by the study team if required
9. Willing to give written informed consent

Exclusion Criteria:

* a. History of or currently meeting DSM-5 criteria for:

  * Any psychotic disorder
  * Bipolar disorder type 1 or 2
  * Major depression with psychotic features
  * Any personality disorders
  * Post-traumatic stress disorder
  * Hallucinogen persisting perception disorder b. A family history of:
  * Schizophrenia or schizoaffective disorder (first- or second-degree relatives), or
  * Bipolar disorder type 1 (first degree relatives) c. Suicide risk according to clinician judgement (e.g. previous suicide attempt or self-harm in the past 6 months) and responses to Columbia Suicide Severity Rating Scale (C-SSRS) and SCID-5-RV.

    d. Abnormal and/or serious clinical finding or medical condition that may preclude participation e. Concurrent use of psychotropic medication e.g., antidepressants, antipsychotics, psychostimulants, treatments for addictions, other dopaminergic or serotonergic agents (e.g. St John's Wort/tryptophan), lithium, anticonvulsants).
  * Use of antidepressants and alcohol pharmacotherapy use considered if assessed by investigator and titrated down with 5 half-lives + 1-week washout f. Use of any medications likely to interact with study medication during the trial (subject to investigator's discretion).
  * Low dose opiates permitted for pain management, however, not the night before or after dosing sessions g. Significant alcohol withdrawal (current CIWA-Ar score ≥10, including history of delirium tremens or alcohol withdrawal seizures).

    h. Any current substance use disorder (SUD) other than tobacco (e.g. opiates, benzodiazepines, cannabis, psychostimulants, hallucinogens) as per clinician judgement and/or defined by DSM-5 criteria (measured by SCID-RV).

    i. Substantial lifetime use (\&gt;25 total) or recent use (past 12 months) of ketamine or classic hallucinogens, such as psilocybin-containing mushrooms or LSD j. Any alcohol pharmacotherapy (e.g. naltrexone, acamprosate) within the past month.

    k. Participation in other clinical trials in the previous two months l. Pregnant or lactating (contraception must be used and a sensitive pregnancy test will be performed at baseline and prior to dosing) m. Allergy or hypersensitivity to psilocybin n. Any condition or factor deemed by the study clinician to place the individual at higher risk of an adverse emotional reaction, severe active stressors such as significant legal problems, marital distress or lack of social support.

Primary outcomes:
measure: Frequency of Heavy Drinking Days (HDD)
timeFrame: 52 Weeks
Secondary outcomes:
measure: Mean alcohol consumption per drinking day
timeFrame: 52 Weeks
measure: Absence of any HDD
timeFrame: 52 Weeks
measure: WHO drinking risk level
timeFrame: 52 Weeks
measure: Dependence Severity
timeFrame: 52 Weeks
measure: Alcohol Craving
timeFrame: 52 Weeks
measure: PEth Levels
timeFrame: 52 Weeks
measure: Changes in Anxiety
timeFrame: 52 Weeks
measure: Changes in Depression
timeFrame: 52 Weeks
measure: Changes in Suicidal Ideation
timeFrame: 52 Weeks
measure: Changes in Quality of Life
timeFrame: 52 Weeks
measure: Markers of Liver Injury
timeFrame: 52 Weeks
Other outcomes:
Locations:
Study officials:
affiliation: University of Sydney
name: Paul Haber, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Sydney
name: Kirsten C Morley, PhD
role: PRINCIPAL_INVESTIGATOR
References: