NCT06349083

Neurobehavioral Mechanisms of Psilocybin-assisted Treatment for Alcohol Use Disorder

Recruiting now Phase 2 Last updated 18 December 2025

What this trial tests

Phase 2 trial testing Psilocybin in Alcohol Use Disorder in 200 participants. Currently enrolling.

Timeline

26 August 2025

Primary endpoint
1 May 2029

1 May 2029

Quick facts

Lead sponsor	NYU Langone Health
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	200
Start date	26 August 2025
Primary completion	1 May 2029
Estimated completion	1 May 2029
Sites	2 locations across United States

Drugs / interventions tested

• Psilocybin — full drug profile →
• Inactive Placebo
• Supportive therapy sessions

Conditions studied

• Alcohol Use Disorder — all drugs for Alcohol Use Disorder →

Sponsor

NYU Langone Health — full company profile →

Who can join

Adults 18 to 65, any sex, with Alcohol Use Disorder. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Percent change in the alcohol cue-induced Blood-oxygen-level dependent (BOLD) signal in the lateral prefrontal cortex (PFC)
  Time frame: Baseline, Day 2
  Percentage change in the BOLD signal is the difference in fMRI signal between the baseline condition (B) and the alcohol cue-induced task condition (T); percent signal change = (T-B)/B×100%. A positive value of the percentage change in BOLD signal indicates up-regulation of BOLD signal.
• Percent change in the alcohol cue-induced BOLD signal change in the caudate
  Time frame: Baseline, Day 2
  Percentage change in the BOLD signal is the difference in fMRI signal between the baseline condition (B) and the alcohol cue-induced task condition (T); percent signal change = (T-B)/B×100%. A positive value of the percentage change in BOLD signal indicates up-regulation of BOLD signal.
• Percent change in alcohol cue-induced BOLD signal change in the ventromedial PFC (vmPFC)
  Time frame: Baseline, Day 2
  Percentage change in the BOLD signal is the difference in fMRI signal between the baseline condition (B) and the alcohol cue-induced task condition (T); percent signal change = (T-B)/B×100%. A positive value of the percentage change in BOLD signal indicates up-regulation of BOLD signal.
• Percent change in alcohol cue-induced BOLD signal change in the insula
  Time frame: Baseline, Day 2
  The blood-oxygen-level-dependent (BOLD) signal, detected in fMRI, reflects changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation, which are coupled to underlying neuronal activity by a process termed neurovascular coupling.
• Percent change in negative affective cue-induced BOLD signal change in the dorsomedial PFC (dmPFC)
  Time frame: Baseline, Day 2
  Percentage change in the BOLD signal is the difference in fMRI signal between the baseline condition (B) and the alcohol cue-induced task condition (T); percent signal change = (T-B)/B×100%. A positive value of the percentage change in BOLD signal indicates up-regulation of BOLD signal.
• Percent change in negative affective cue-induced BOLD signal change in the supramarginal gyrus
  Time frame: Baseline, Day 2
  Percentage change in the BOLD signal is the difference in fMRI signal between the baseline condition (B) and the negative affective cue-induced task condition (T); percent signal change = (T-B)/B×100%. A positive value of the percentage change in BOLD signal indicates up-regulation of BOLD signal.

Sponsor's own description

This is a double-blind, randomized, placebo-controlled Phase 2 mechanistic clinical trial designed to evaluate the therapeutic neural mechanisms of psilocybin in patients with alcohol use disorder (AUD), and to determine whether further studies are warranted to study the relationship of any such effects to clinical improvement in AUD symptoms. The primary aims are to evaluate the effects of psilocybin on AUD; measures will include 1) fMRI neural activation and functional connectivity, using a well-validated task to characterize neural and subjective response to negative affective and alcohol visual stimuli; 2) alcohol use data (self-report and blood biomarkers); and 3) self-report measures related the NE, IS, and EF domains.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Emerging medications and pharmacological treatment approaches for substance use disorders.
   Raymond JS, Athanasopoulos AG, Badolato CJ, Doolan TJ, et al · · 2025 · cited 2× · PMID 39719161 · DOI 10.1016/j.pbb.2024.173952
2. Pharmacological interventions for alcohol use disorder: novel insights from recent clinical trials.
   McManus KR, Ray LA. · · 2026 · PMID 41611606 · DOI 10.1080/17512433.2026.2625341
3. A Tragedy of Errors: The State of Psychedelic Research in the Treatment of Alcohol Use Disorder.
   Srivastava AB, Gold MS. · · 2025 · PMID 41300197 · DOI 10.3390/brainsci15111190