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

Introduction

Cazorla and colleagues frame the study around the need for objective biomarkers to characterise pharmacodynamic effects and predict response in LSD-assisted psychotherapy for major depressive disorder (MDD). They note that LSD acts mainly via partial agonism at 5-HT2A receptors and that this receptor-mediated cascade can include release of neuropeptides such as oxytocin, which is implicated in social bonding, stress modulation and psychological flexibility. Prior work in healthy volunteers found rises in plasma oxytocin 90–180 minutes after oral LSD, and preclinical rodent studies showed 5-HT2A-dependent oxytocin release; however, oxytocin dynamics have not been characterised in psychiatric patients, and salivary oxytocin (a minimally invasive option suitable for repeated sampling) had not been evaluated during LSD administration. This pilot observational study therefore aimed to describe salivary oxytocin trajectories across the acute pharmacodynamic window of a single LSD-assisted psychotherapy session in patients with treatment-resistant MDD. A secondary, exploratory aim was to record concurrent momentary ratings of subjective drug intensity, to compare temporal patterns between oxytocin release and perceived psychedelic effects. The investigators positioned this work as feasibility data to inform larger, controlled trials that could test whether oxytocin reactivity relates to clinical outcomes or patient stratification.