Psilocybin for Depression in Veterans

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.