ArticleBJPsych open2025
Sustained mood improvement with laughing gas exposure (SMILE): a randomised, placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression.
Article in BJPsych open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07262008 (Sustained Mood Improvement With Laughing Gas Exposure), which is not on this map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Double-Blind Trial
Who cites it
2 citing papers in PubMed.
- Article
- Rapid antidepressant potential of nitrous oxide: current state and major questions.Molecular psychiatry · 2026Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNitrous oxide may possess antidepressant effects; however, limited data exist on repeated administrations and active placebo-controlled studies in treatment-resistant depression (TRD).
aimsWe aimed to test the feasibility of a randomised controlled trial examining a 4-week course of nitrous oxide or midazolam, an active placebo.
methodIn this randomised, active, placebo-controlled pilot trial, 40 participants with TRD were assigned either a 1-h inhalation of 50% nitrous oxide plus intravenous saline (
resultsThe recruitment rate was 22.3% (95% CI 16.9-29.0). Withdrawal rates were 10% (95% CI 2.8-30.1) in both groups and adherence rates were 100.0% (95% CI 82.4-100) in the nitrous oxide group and 94.4% (95% CI 74.2-99.0) in the placebo group. There were no missing primary clinical outcome data in either group (0.0%, 95% CI 0.0-17.6). MADRS score changed by -20.5% (95% CI -39.6 to -1.3) in the nitrous oxide group and -9.0% (95% CI -22.6 to 4.6) in the placebo group. Nearly all adverse events were mild to moderate and transient.
conclusionsThe findings support the feasibility and necessity of conducting a full-scale trial comparing nitrous oxide and midazolam in patients with TRD.
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