Ignite Creation Date:
2025-12-24 @ 4:02 AM
Ignite Modification Date:
2025-12-24 @ 4:02 AM
Study NCT ID:
NCT07296094
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-12-22
First Post:
2025-12-12
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Psilocybin-Assisted Psychotherapy for the Treatment of Severe Alcohol Use Disorder
Sponsor:
Brigham and Women's Hospital
Organization:
Study Overview
Official Title:
Psilocybin-Assisted Psychotherapy for the Treatment of Severe Alcohol Use Disorder: A Double-Blind, Dose-Comparison Concurrent Control Randomized Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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).
Detailed Description:
This study is a double-blind, dose-comparison concurrent control randomized trial designed to evaluate the effects of psilocybin-assisted psychotherapy on alcohol-related outcomes, neurocognitive processes related to craving and stress, and neural circuits involved in reward and regulation among adults with severe alcohol use disorder (AUD). Participants are recruited up to 3 months after completing inpatient alcohol withdrawal treatment to ensure medical stabilization prior to psilocybin administration. The study examines both preliminary efficacy and safety while also exploring mechanistic pathways through behavioral assessments and functional neuroimaging.
Participants (N=36) are randomized in a 1:1 ratio to receive either a full-dose psilocybin (30 mg, with option to escalate to 40 mg on the second session) or a low-dose (10 mg, with option to escalate to 15 mg on the second session). All participants complete two dosing sessions spaced four weeks apart. The psychotherapy is delivered by a dyad of trained therapists before, during, and after the dosing sessions and is based on established therapeutic frameworks used in prior psilocybin-assisted therapy trials. The aim of the therapeutic support is to prepare participants for the psilocybin experience, facilitate psychological processing during and after dosing, and support integration of insights into daily life.A peer recovery coach is integrated into the study to support relapse prevention, enhance coping skills, and encourage engagement in ongoing addiction treatment. All participants are offered follow-up services at the institution's outpatient addiction treatment program (including the BWH Bridge Clinic), regardless of study arm. This combination of medical oversight, psychotherapy, and recovery support reflects an effort to embed the intervention within real-world addiction care settings.
Alcohol-related outcomes are assessed repeatedly from baseline through 48 weeks after the second dosing session. The primary clinical outcome is the percentage of heavy drinking days during the 24-week follow-up period, measured using Timeline Follow-Back. Secondary alcohol outcomes include drinking quantity and frequency, relapse timing, direct alcohol biomarkers (phosphatidylethanol and ethylglucuronide), withdrawal symptoms, treatment expectancy, blinding integrity, and quality of life measures. Additional exploratory outcomes assess peer support engagement and 12-step attendance.
Safety is evaluated throughout the study using structured assessments of adverse events, vital signs, and mood and anxiety symptoms. Because participants have severe AUD and recent withdrawal treatment, careful medical screening is conducted prior to each dosing session. The study includes multiple follow-up assessments up to 48 weeks after the second psilocybin dose, allowing characterization of both acute and longer-term safety.
Two mechanistic components are incorporated. First, neurocognitive tasks assess cue-induced craving, attentional bias, stress reactivity, delayed discount, decision making, and distress tolerance. These measures evaluate whether psilocybin influences cognitive and affective processes known to contribute to alcohol use and relapse. Second, participants complete two fMRI scans-first within one week prior to the first dosing session and the second within one week after the second dosing session. The fMRI tasks evaluate neural response to alcohol-related cues and the ability to down-regulate craving, focusing on the nucleus accumbens (NAcc) and dorsolateral prefrontal cortex (DLPFC). Connectivity analyses examine changes in functional coupling between these regions during alcohol cue processing.
Together, these approaches allow the study to evaluate whether full-dose psilocybin, compared to low-dose, produces greater reductions in heavy drinking and craving, whether the treatment is safe and tolerable for individuals with severe AUD, and whether changes in cognitive, emotional, and neural functioning help explain clinical outcomes. By recruiting individuals immediately following inpatient detoxification, the study also examines the feasibility of incorporating psilocybin-assisted therapy into a critical window of early recovery. Results will inform whether a larger, fully powered clinical trial is justified and will contribute to the broader understanding of psilocybin's therapeutic potential in alcohol use disorder.
Participants (N=36) are randomized in a 1:1 ratio to receive either a full-dose psilocybin (30 mg, with option to escalate to 40 mg on the second session) or a low-dose (10 mg, with option to escalate to 15 mg on the second session). All participants complete two dosing sessions spaced four weeks apart. The psychotherapy is delivered by a dyad of trained therapists before, during, and after the dosing sessions and is based on established therapeutic frameworks used in prior psilocybin-assisted therapy trials. The aim of the therapeutic support is to prepare participants for the psilocybin experience, facilitate psychological processing during and after dosing, and support integration of insights into daily life.A peer recovery coach is integrated into the study to support relapse prevention, enhance coping skills, and encourage engagement in ongoing addiction treatment. All participants are offered follow-up services at the institution's outpatient addiction treatment program (including the BWH Bridge Clinic), regardless of study arm. This combination of medical oversight, psychotherapy, and recovery support reflects an effort to embed the intervention within real-world addiction care settings.
Alcohol-related outcomes are assessed repeatedly from baseline through 48 weeks after the second dosing session. The primary clinical outcome is the percentage of heavy drinking days during the 24-week follow-up period, measured using Timeline Follow-Back. Secondary alcohol outcomes include drinking quantity and frequency, relapse timing, direct alcohol biomarkers (phosphatidylethanol and ethylglucuronide), withdrawal symptoms, treatment expectancy, blinding integrity, and quality of life measures. Additional exploratory outcomes assess peer support engagement and 12-step attendance.
Safety is evaluated throughout the study using structured assessments of adverse events, vital signs, and mood and anxiety symptoms. Because participants have severe AUD and recent withdrawal treatment, careful medical screening is conducted prior to each dosing session. The study includes multiple follow-up assessments up to 48 weeks after the second psilocybin dose, allowing characterization of both acute and longer-term safety.
Two mechanistic components are incorporated. First, neurocognitive tasks assess cue-induced craving, attentional bias, stress reactivity, delayed discount, decision making, and distress tolerance. These measures evaluate whether psilocybin influences cognitive and affective processes known to contribute to alcohol use and relapse. Second, participants complete two fMRI scans-first within one week prior to the first dosing session and the second within one week after the second dosing session. The fMRI tasks evaluate neural response to alcohol-related cues and the ability to down-regulate craving, focusing on the nucleus accumbens (NAcc) and dorsolateral prefrontal cortex (DLPFC). Connectivity analyses examine changes in functional coupling between these regions during alcohol cue processing.
Together, these approaches allow the study to evaluate whether full-dose psilocybin, compared to low-dose, produces greater reductions in heavy drinking and craving, whether the treatment is safe and tolerable for individuals with severe AUD, and whether changes in cognitive, emotional, and neural functioning help explain clinical outcomes. By recruiting individuals immediately following inpatient detoxification, the study also examines the feasibility of incorporating psilocybin-assisted therapy into a critical window of early recovery. Results will inform whether a larger, fully powered clinical trial is justified and will contribute to the broader understanding of psilocybin's therapeutic potential in alcohol use disorder.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: