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Sustained mood improvement with laughing gas exposure (SMILE): a randomised, placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression: commentary, Kalmar et al

Alain F. Kalmar, Pascal Sienaert, Filip Bouckaert, Steffen Rex

BJPsych Open July 1, 2026 DOI: 10.1192/bjo.2026.12040 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Review Randomized Placebo-controlled Pilot study Peer reviewed
Duration 1 h treatment, per patient-year
Topics Depression
Keywords Nitrous oxide Greenhouse gas Mood Externality Inhalation Randomized controlled trial Anesthesia
Key findings A single one-hour nitrous oxide treatment for depression generates about 150 kg CO2-equivalents, rising to about 7.8 t per patient-year, and these environmental externalities should be incorporated into evaluation.

Abstract

Summary Nitrous oxide is being investigated as a treatment for therapy-resistant depression, yet its environmental implications as a potent greenhouse gas are largely unaddressed. A single 1 h treatment generates ∼150 kg CO 2 -equivalents, rising to ∼7.8 t per patient-year, highlighting the need to incorporate environmental externalities into evaluation.