Salivary Oxytocin as a Biomarker of Psychedelic Treatment

This observational trial (n=80) will investigate whether salivary oxytocin reactivity during a psychedelic-assisted psychotherapy session predicts treatment response in adults with treatment-resistant major depressive disorder (MDD), by examining its relationship with changes in psychological flexibility and depressive symptoms. The study will enrol an estimated 80 participants aged ≥18 years who meet DSM‑5 criteria for MDD and are receiving ongoing classical psychotherapy; participants must agree to discontinue necessary psychotropic medications though some classes of antidepressants are permitted without tapering. Key exclusions include psychotic or bipolar disorder, high suicidal risk, severe cardiovascular, hepatic or central nervous system disorders, and pregnancy or breastfeeding. The primary outcome is salivary oxytocin measured one day; the protocol will assess associations between oxytocin reactivity during the psychedelic session and subsequent changes in flexibility and depressive symptoms. The trial is sponsored by the University of Geneva and is scheduled from 2026-01-05 to 2026-10-30 (enrolling by invitation).