Pilot Data on Salivary Oxytocin as a Biomarker of LSD Response in Patients with Major Depressive Disorder
Aboulafia-Brakha, T., Alaux, S., Amberger, C., Buchard, A., Cazorla, L., Furtado, L., Mabilais, C., Penzenstadler, L., Thorens, G., Zullino, D.
This pre-print reports an observational pilot study (n=12) examining salivary oxytocin ('love/bonding hormone') dynamics during LSD-assisted psychotherapy (100-150μg) for treatment-resistant depression (TRD), finding significant time-dependent variations in both oxytocin levels and subjective drug intensity ratings, suggesting oxytocin may serve as a potential biomarker for psychedelic therapy.
Abstract
Despite growing evidence supporting the efficacy of LSD-assisted psychotherapy in treating major depressive disorder (MDD), identifying reliable psychopharmacological biomarkers remains necessary. Oxytocin, a neuropeptide implicated in social bonding and flexibility, is a promising candidate due to its release following serotonergic psychedelic administration in healthy individuals; however, its dynamics in psychiatric populations are currently unexplored. This observational pilot study aimed to characterize salivary oxytocin dynamics during a single LSD-assisted psychotherapy session in our patients 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, participants 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 psychedelic 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.