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

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.

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.

Individual Participant Data (IPD) might not be shared due to privacy concerns, potential misuse of data, intellectual property rights, and ethical considerations. Additionally, legal restrictions and the need to protect sensitive information can also limit the sharing of IPD.

Double blinded with an additional optional dosing session for open label dosing