Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression

This Phase III, randomised, quadruple‑masked, parallel trial (n=240) will evaluate the efficacy and risks of psilocybin for treatment‑resistant depression in U.S. military veterans with and without concurrent post‑traumatic stress disorder, with the primary outcome being change in the Montgomery‑Åsberg Depression Rating Scale (MADRS) at 2 weeks. This multi‑site study randomises participants to either a psilocybin intervention dose or a psilocybin comparator dose under blinded conditions. Consenting veterans will receive two psilocybin dosing sessions with psychological preparation, administration and integration support from a facilitator; participants are randomised at the first administration to one of the two doses and one month later all participants receive a 25 mg dose at the second session. Outcomes are measured by an independent evaluator masked to treatment at 2 and 4 weeks after each dosing session, with longer‑term follow‑up over 6 months, and both expected and unanticipated adverse events collected. Key eligibility includes English‑speaking U.S. veterans aged 18–75 years with a current major depressive episode (MADRS ≥20) who have not responded to ≥2 adequate antidepressant treatments.