Pilot Data on Salivary Oxytocin as a Biomarker of LSD Response in Patients with Major Depressive Disorder

Despite growing evidence supporting the efficacy of LSD-assisted psychothera-py in treating major depressive disorder (MDD), identifying reliable psychopharmacolog-ical biomarkers remains necessary. Oxytocin, a neuropeptide implicated in social bonding and flexibility, is a promising candidate due to its release following serotonergic psyche-delic administration in healthy individuals; however, its dynamics in psychiatric popula-tions are currently unexplored. This observational pilot study aimed to characterize sali-vary oxytocin dynamics during a single LSD-assisted psychotherapy session in our pa-tients with treatment-resistant MDD. Participants received 100 or 150 µg LSD and salivary oxytocin was measured at baseline, 60, 90, and 180 minutes post-LSD. Concurrently, par-ticipants rated subjective drug intensity (0-10 scale) at 60, 90, and 180 minutes. A linear mixed model revealed significant variation of oxytocin levels over time. Perceived psy-chedelic intensity also significantly varied over time. This supports oxytocin as a potential biomarker. Larger, controlled trials are warranted to replicate these findings and clarify mechanistic links between oxytocin dynamics and clinical outcomes, including changes in depressive symptoms and mental flexibility.