Psilocybin for Depression in Veterans

Brief summary

More efficacious treatments for Major Depressive Disorder (MDD) in Veterans are urgently needed. Psilocybin is a promising novel treatment that is likely to be the first FDA-approved psychedelic, but its safety and efficacy remain unclear. To address this gap, the investigators propose a randomized controlled trial of a single dose of psilocybin paired with a brief course of a VA-endorsed evidence-based psychotherapy (Acceptance and Commitment Therapy) in Veterans with MDD. Our trial addresses key limitations of previous studies including the challenge of management of expectancy effects, a focus on Veterans with input from Veterans, and a study population that reflects the demographics and medical and psychiatric complexity of the VHA patient population. Our study also explores psilocybin's antidepressant mechanisms focusing on changes in psychological flexibility and synaptic plasticity. In sum, this study will provide critical and timely data to determine if psilocybin treatment is a safe and efficacious treatment for MDD in Veterans.

Source: ClinicalTrials.gov (U.S. National Library of Medicine), data processed 2026-10-29T09:00:05; modifications: selected fields only; whitespace normalized; brief summary truncated to 2,000 characters. Not a U.S. Government endorsement.

Trial details

acronym

PACT

status

NOT_YET_RECRUITING

phase

PHASE2

study type

INTERVENTIONAL

enrollment

150

sponsor

VA Office of Research and Development

conditions

Major Depression

interventions

DRUG: Psilocybin; DRUG: modafinil; DRUG: zolpidem; DRUG: pimavanserin

start date

2027-01-01

start date type

ESTIMATED

primary completion date

2031-12-31

has results

false

data source

ClinicalTrials.gov

data processed

2026-10-29T09:00:05

modifications

selected fields only; whitespace normalized; brief summary truncated to 2,000 characters