Suicidal thoughts and behaviours are linked to a wide range of mental health conditions. New interest in the psychiatric benefits of nitrous oxide (N₂O) has only recently emerged. The broad pharmacological effects of N₂O are thought to be due in large part to N-methyl-d-aspartate antagonism and opioid effects. The purpose of this study protocol is to test whether inhalational N₂O exerts rapid antisuicidal effects as a transdiagnostic treatment for suicidal ideation.

This is the protocol of a single-centre pilot study of N₂O inhalation in 85 psychiatric inpatients. The initial 45-min double-blind, randomised, placebo-controlled inhalation session either consists of 50% N₂O and 50% oxygen (‘active treatment’) or 50% oxygen plus air. The primary outcome is the change in Beck Scale for Suicidal Ideation scores between the day before and the day after inhalation. A second inhalation containing N₂O will be administered 1 week after the first inhalation to ensure that all study participants receive the active treatment at least once. For the mechanism of action and prediction, a nested biomarker substudy will employ multimodal techniques, including analysis of hair and blood samples and electroencephalography.

This study was approved by the local ethics committee (‘Kantonale Ethikkommission—Kanton Zürich’) and by the Swiss Agency for Therapeutic Products (Swissmedic). Study results will be disseminated primarily by peer-reviewed scientific journals and also by conference presentations, patient and public events and social media.

ClinicalTrials.gov ID NCT06636357.