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

L. Cazorla, Sylvie Alaux, Caroline Amberger, Cédric Mabilais, Leonice Furtado, Albert Buchard, Gabriel Thorens, Louise Penzenstadler, Daniele Zullino, Tatiana Aboulafia Brakha

Psychoactives August 1, 2025 DOI: 10.3390/psychoactives4030026 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational pilot study Peer reviewed
Population Patients with treatment-resistant major depressive disorder
Intervention LSD-assisted psychotherapy
Dose 100 or 150 µg LSD
Duration Single session with measurements at baseline, 60, 90, and 180 minutes post-LSD
Topics Depression LSD
Key findings Salivary oxytocin levels varied significantly over time during a single LSD-assisted psychotherapy session in patients with treatment-resistant MDD.

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 min post-LSD. Concurrently, participants rated subjective drug intensity (0–10 scale) at 60, 90, and 180 min. 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 the mechanistic links between oxytocin dynamics and clinical outcomes, including changes in depressive symptoms and mental flexibility.

Comparable studies

Other non-randomized and open-label trials on LSD for depression, most cited first.

Study Year Design Participants
An open-label pilot trial assessing tolerability and feasibility of LSD microdosing in patients with major depressive disorder (LSDDEP1). Patients with major depressive disorder meeting DSM-5 criteria 2023 Open-label pilot trial n = 20
LSD microdosing in major depressive disorder: results from an open-label trial Participants with major depressive disorder, most taking antidepressant medication 2025 Open-label phase 2A trial n = 19
LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial People with depression 2026 Clinical trial
What is it like to microdose LSD for depression? a thematic analysis of participant interviews from an open-label trial. Adults with major depressive disorder 2025 Open-label pilot trial (phase IIa) with post-intervention qualitative interviews n = 17
155. EXPLORING LSD MICRODOSING IN AN OPEN-LABEL PILOT FOR MAJOR DEPRESSIVE DISORDER: THE INTERPLAY OF BEHAVIORAL ACTIVATION, MOOD IMPROVEMENT, AND CONNECTEDNESS Individuals with major depressive disorder 2025 Open label trial n = 17

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