Psilocybin-Assisted Psychotherapy for the Treatment of Severe Alcohol Use Disorder

NCT07296094 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2025P002909
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine the safety and preliminary efficacy of psilocybin-assisted psychotherapy in improving alcohol-related outcomes among adults with severe alcohol use disorder in a a double-blind, dose-comparison concurrent control, randomized trial. Participants will undergo structured psychotherapy and will be randomized to two psilocybin sessions to receive either a full dose (30mg or 40mg) or low dose (10mg or 15mg).

Conditions

Alcohol Use Disorder

Keywords

alcohol use disorder; psilocybin; inpatient withdrawal management; psychedelic

Outcome Measures

Primary Outcomes (6)

• Percent Heavy Drinking Days

  Percent Heavy Drinking Days (PHDD) is defined as the percentage of days in which participants engage in heavy drinking, calculated using the Timeline Follow-Back (TLFB) method. Heavy drinking is defined using NIAAA criteria (≥4 drinks/day for women; ≥5 drinks/day for men). PHDD will be analyzed as a continuous outcome to compare change over time between the full-dose and low-dose psilocybin groups.

  Weeks 0-24 following the first psilocybin dosing session.

• Adverse effects

  We will utilize the Patient-Rated Inventory of Side Effects to assess the frequency and severity of adverse effects.

  1, 2, 4, 8, 16, 24 and 48 weeks after receiving the second dose of the psilocybin treatment.

• Cue-Induced Craving Response

  Craving intensity elicited by alcohol-related visual cues during a standardized cue-reactivity task as measured using a visual analog scale. The scale is titled Cue induced Craving scale and is measured from 0-10, 0 being Not at all and 10 being extremely craving. A higher score indicates more craving of the substance shown.

  Measured at baseline, 4 and 24 weeks after the second psilocybin treatment.

• Neural Response and Connectivity Changes measured by fMRI

  BOLD response in the nucleus accumbens (NAcc) to alcohol-related images during craving.

  1 week before and 1 week after the second psilocybin session

• Neural Response and Connectivity Changes measured by fMRI

  BOLD response in the dorsolateral prefrontal cortex (DLPFC) during down-regulation of craving.

  1 week before and 1 week after the second psilocybin session

• Neural Response and Connectivity Changes measured by fMRI

  NAcc-DLPFC functional connectivity during alcohol cue processing.

  1 week before and 1 week after the second psilocybin session

Secondary Outcomes (28)

• Percent Days Abstinent

  Baseline to Weeks 24

• Drinks Per Drinking Day

  Baseline to Week 24

• Vital signs

  Baseline to Week 48

• MEQ30 - Mystical Experience Questionnaire.

  Visit 6 & 10 (about 4 weeks in between visits 6 and 10)

• Altered states of consciousness

  Immediately after each drug session

Study Arms (2)

Low Dose Psilocybin

ACTIVE COMPARATOR

Participants randomized to this arm receive psilocybin in capsule form at a dose of 10 mg during the first dosing session, with the option to increase to 15 mg at the second session. Doses are administered orally under direct supervision in a controlled clinical setting and paired with the same standardized psychotherapy protocol used in the high-dose arm. Participants complete two dosing sessions four weeks apart and receive ongoing support from a peer recovery coach and optional outpatient addiction treatment.

Drug: Psilocybin

Full Dose Psilocybin

EXPERIMENTAL

Participants randomized to this arm receive psilocybin in capsule form at a dose of 30 mg during the first dosing session, with the option to increase to 40 mg at the second session. Doses are administered orally under direct supervision in a controlled clinical setting and paired with a standardized psychotherapy protocol, including preparatory and integration sessions. All participants complete two dosing sessions spaced four weeks apart and receive ongoing support from a peer recovery coach and optional outpatient addiction treatment.

Drug: Psilocybin

Interventions

Psilocybin DRUG

Psilocybin is administered in oral capsule form during two dosing sessions held four weeks apart. Each session occurs in a controlled clinical environment with continuous monitoring by trained study therapists. Participants receive a standardized psychotherapy protocol that includes preparatory sessions before dosing and integration sessions afterward. The randomized dosing schedule includes either 10 mg with optional escalation to 15 mg or 30 mg with optional escalation to 40 mg for the second session. All participants also receive support from a peer recovery coach and are offered ongoing outpatient addiction treatment throughout the study period.

Full Dose Psilocybin; Low Dose Psilocybin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

To be eligible, individuals must be: * English speaking adults between ages 18 and 65 * Diagnosis of DSM5 AUD, severe * Completion of inpatient withdrawal management (i.e. "detox") for AUD within 90 days of enrollment * Amenable to attending all psychotherapy and study visits at BWH CCI * Able to identify an individual who can act as points of contact during the trial * Have a friend or family member who can bring the participant home after the psilocybin sessions and stay overnight Individuals with any of the following will be excluded: * Any personal history of a psychotic disorder (schizophrenia, schizoaffective disorder, brief psychotic disorder, delusional disorder, schizophreniform disorder, substance-induced psychotic disorder or major depression with psychotic features) or any bipolar-spectrum disorder * Participants with a family history of first-degree relatives with psychotic disorder or bipolar-spectrum disorder * Participants who have a significant suicide risk as defined by current suicidal ideation (Columbia-Suicide Severity Rating Scale (C-SSRS) score 2 to 5) and/or recent (within the past 6 months) active suicidal ideation (C-SSRS score 4 or 5) * Participants who have a history of significant or serious adverse reaction to classic psychedelics * Homicidality within the last six months * History of DSM5 hallucinogen use disorder * Positive blood alcohol level at screening * Need for inpatient withdrawal management for alcohol at the time of screening * Current DSM5 opioid, cocaine, stimulant or sedative/hypnotic use disorder * Systolic blood pressure persistently above 165mmHg during screening * History of hypersensitivity to psilocybin * Use of psilocybin or other psychedelics with 5-HT2B activity in the prior 12 months * Significant EKG abnormalities including QTc prolongation defined as \>450 ms for men and women, or a diagnosis or family history of Long QT syndrome. * History of any cardiac valvulopathy that raises the risk for participation as determined by the cardiology consultant * History of intracranial mass or bleed, seizure disorder other than alcohol withdrawal seizures, liver cirrhosis, renal failure, obstructive lung disease requiring supplemental oxygen, hyperthyroidism, narrow-angle glaucoma, uncontrolled cardiac arrythmias, heart failure * History of head trauma, stroke, or myocardial infarction in one year prior to enrollment. * Expected to require surgical treatment at any point during the trial * Liver dysfunction with LFTs \> 3x upper normal limit at screening and Total bilirubin \> 2.5x the upper normal limit * MRI contraindications (other ferromagnetic implants, body weight greater than 550 lbs., etc.) * Pregnant or breastfeeding * High risk for adverse emotional or behavioral reaction based on the opinion of the study investigators such as evidence of a personality disorder * Currently taking medications with serotonergic activity (other than SSRIs/SNRIs); inhibitors of UGT1A9, UGT1A10, MAO, and aldehyde or alcohol dehydrogenase; antipsychotics (e.g., first and second generation); mood stabilizers (e.g., lithium, valproic acid); or significant inhibitors of UGT enzymes that metabolize psilocin * Selective serotonergic reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors are allowed if participants have been on stable doses of the medication(s) for at least 30 days prior to enrollment.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Joji Suzuki, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joji Suzuki, MD

CONTACT

617-732-5752; jsuzuki2@bwh.harvard.edu

Zack Sager, MD

CONTACT

ZacharyS_Sager@DFCI.HARVARD.EDU

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This trial uses double-blind masking. Participants, therapists, clinical staff present during dosing sessions, outcome assessors, and study investigators are all masked to treatment assignment. The psilocybin doses are prepared and dispensed by unmasked pharmacy personnel who have no contact with participants and no role in assessments or data analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This study uses a double-blind, parallel-group, dose-comparison concurrent control, randomized trial design. Participants are randomly assigned in a 1:1 ratio to receive two sessions of either a full dose (30 mg with optional escalation to 40 mg) or a low dose (10 mg with optional escalation to 15 mg). All participants receive two dosing sessions four weeks apart, along with a standardized psychotherapy protocol delivered before, during, and after each session. Outcomes are assessed repeatedly from baseline through 48 weeks after the second dose, allowing evaluation of both clinical effects and mechanistic changes over time.

Study Record Dates

• First Submitted: December 12, 2025
• First Posted: December 22, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): February 1, 2030
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

US (1)