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.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cites 2
- Sustained mood improvement with laughing gas exposure (SMILE): a randomised, placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression. BJPsych Open September 12, 2025
- Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study. Molecular Psychiatry September 1, 2023