Nitrous oxide for the treatment of depression: a systematic review and meta-analysis.
EBioMedicine December 1, 2025 Kiranpreet Gill, Angharad N De Cates, Chantelle Wiseman et al.
Nitrous oxide, a gas that blocks the N-methyl-d-aspartate receptor, shows rapid but short-lived antidepressant effects in early-phase trials. Pooled results from three trials using a single 50% dose found significant reductions in depressive symptoms at 2 hours and 24 hours after inhalation, but not at one week. Side effects were mild and temporary, with the 25% dose being better tolerated. Most trials were small, early-phase studies focused on short-term outcomes in adults with major depressive disorder or treatment-resistant depression. Whether nitrous oxide will become a useful clinical treatment depends on whether its effects can be sustained through optimized or repeated dosing.