Psilocybin-assisted Therapy for Alcohol Use Disorder

Depression Clinical Trial

Official title:

A Multi-centre, Double-blinded, Placebo-controlled, Randomised, Phase II Clinical Trial for Psilocybin-assisted Therapy for Alcohol Use Disorder

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06444243
• Other study ID #: X23-0055
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 2024
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: University of Sydney
• Contact: Kirsten C Morley, PhD
• Phone: 95153636
• Email: Kirsten.morley[@]sydney.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: December 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (>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.

Related Conditions & MeSH terms

• Alcohol Dependence
• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• Anxiety
• Depression

Intervention

Drug:
• Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi.
• Niacin
A nutrient in the vitamin B complex that the body needs in small amounts to function and stay healthy. Niacin helps some enzymes work properly and helps skin, nerves, and the digestive tract stay healthy. Niacin is found in many plant and animal products. Niacin will be used at a concentration of 250mg as an active control.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Sydney	Woke Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Heavy Drinking Days (HDD)	Frequency of HDD as measured by the Timeline Follow Back (TLFB) and validated by Phosphatidylethanol (PEth). HDD are defined as =4 drinks/day for women and =5 drinks/day for men.	52 Weeks
Secondary	Mean alcohol consumption per drinking day	The mean alcohol consumption per drinking day will be gathered reported as the number of standard drinks consumed each day.	52 Weeks
Secondary	Absence of any HDD	Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels	52 Weeks
Secondary	WHO drinking risk level	The WHO categorizes alcohol consumption into different risk levels based on average daily intake and associated health risks: Abstainer: Rarely or never drinks alcohol. Low-risk drinking: (Men: Up to 2 standard drinks per day, Women: Up to 1 standard drink per day). Moderate-risk drinking: (Men: 3-4 standard drinks per day, Women: 2-3 standard drinks per day). High-risk drinking: (Men: More than 4 standard drinks per day, Women: More than 3 standard drinks per day). Heavy episodic (binge) drinking: 60 grams (5-6 drinks) or more on a single occasion.	52 Weeks
Secondary	Dependence Severity	Alcohol Dependence Scale (ADS) is a measure of the severity of the participant's dependence on alcohol. The measure contains 29 items regarding symptoms and occurrences associated with dependence on alcohol. A total score for the measure is yielded by adding across items. Higher scores indicate more severe dependence.	52 Weeks
Secondary	Alcohol Craving	Alcohol craving will be investigated using the Penn Alcohol Craving Scale (PACS). The PACs is a 5-item questionnaire that measures an individual's craving to drink alcohol in the past week.	52 Weeks
Secondary	PEth Levels	PEth measures the level of phosphatidylethanol, a direct alcohol biomarker which is found in human blood following alcohol consumption. Phosphatidylethanols are abnormal phospholipids formed in the presence of ethanol	52 Weeks
Secondary	Changes in Anxiety	Measured by cumulative scores on the DASS-21 Anxiety Scale. This scale has a minimum score of 0 and maximum score of 21. A higher score indicates more anxiety.	52 Weeks
Secondary	Changes in Depression	Measured by cumulative scores on the DASS-21 Depression Scale. This scale has a minimum score of 0 and maximum score of 21. A higher score indicates greater depression.	52 Weeks
Secondary	Changes in Suicidal Ideation	Changes in suicidal ideation & behaviours across the treatment period. This will be measured on the C-SRSS (Columbia Suicide Severity Rating Scale). At baseline this will be measured by the baseline version. At each visit following this, this will be recorded on the since last visit version. Higher scores indicate more severe suicidality.	52 Weeks
Secondary	Changes in Quality of Life	To assess whether treatment can change quality of life as measured by the short form Health Survey (SF-36). This survey has 36 items that measure 8 domains of health, including: physical functioning, physical role limitations, bodily pain, general health perceptions, energy/vitality, social functioning, emotional role limitations and mental health. The scores are transformed to range from 0 (worst possible health) to 100 (best possible health).	52 Weeks
Secondary	Markers of Liver Injury	An assortment of liver enzymes will be monitored throughout the trial to investigate any changes that occur in liver function.	52 Weeks