A common "laughing gas" may hold serious promise for depression treatment. A major meta-analysis led by the University of Birmingham has found that nitrous oxide-better known for its use in dental procedures and surgeries-can rapidly ease symptoms of major depression, including treatment-resistant cases, often within just 24 hours. Published in eBioMedicine, the study points to nitrous oxide as a potential new addition to next-generation antidepressants.
Major depressive disorder (MDD) affects millions worldwide, yet nearly half of all patients gain little or no benefit from standard antidepressants. When two or more drug treatments fail, the condition is known as treatment-resistant depression (TRD)—a particularly stubborn form that leaves patients struggling for years. Scientists are now exploring therapies that act faster and more directly on the brain’s chemistry, and nitrous oxide is emerging as a promising candidate.
The Birmingham-led team reviewed seven clinical trials and four ongoing protocols conducted around the world, covering patients with MDD, TRD, and bipolar depression. The studies compared how single versus repeated doses of nitrous oxide affected mood and symptom relief. When participants inhaled nitrous oxide at 50% concentration, many experienced noticeable mood improvements within a day, though the effects from a single session faded within a week. Remarkably, those who received repeated treatments over several weeks maintained longer-lasting benefits, suggesting that a structured multi-session approach could enhance recovery.
Nitrous oxide appears to work by targeting glutamate receptors in the brain—the same chemical pathway influenced by ketamine, another fast-acting antidepressant. This mechanism allows for rapid modulation of mood-regulating circuits, leading to quick relief from depressive symptoms.
The analysis also confirmed a reassuring safety profile. Short-term side effects like dizziness, nausea, or headaches were mild and temporary. No major safety concerns were reported, although researchers emphasize the need for larger trials to evaluate long-term use and dosing precision.
Researchers are now preparing the first NHS clinical trial to explore safe delivery of nitrous oxide as a treatment for severe depression. If successful, this approach could bring hope to those whom conventional treatments have failed—offering a fast, noninvasive, and potentially life-changing new option.
REFERENCE: Kiranpreet Gill, Angharad N. de Cates, Chantelle Wiseman, Susannah E. Murphy, Ella Williams, Catherine J. Harmer, Isabel Morales-Muñoz, Steven Marwaha. Nitrous oxide for the treatment of depression: a systematic review and meta-analysis. eBioMedicine, 2025; 106023 DOI: 10.1016/j.ebiom.2025.106023
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