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The boon and bane of nitrous oxide.

Golo Kronenberg, Georgios Schoretsanitis, Erich Seifritz, Sebastian Olbrich

European Archives of Psychiatry and Clinical Neuroscience September 1, 2025 DOI: 10.1007/s00406-024-01801-3 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Topics Depression
Keywords Abuse Homocysteine Methylmalonic acid Nitrous oxide Rapid antidepressant effects
Key findings Nitrous oxide shows potential as a rapid-acting antidepressant, but larger trials are needed to confirm its efficacy and optimal use.

Abstract

Nitrous oxide (N2O) has been known since the end of the eighteenth century. Today, N2O plays a huge role as a greenhouse gas and an ozone-depleting stratospheric molecule. The main sources of anthropogenic N2O emissions are agriculture, fuel combustion, wastewater treatment, and various industrial processes. By contrast, the contribution of medical N2O to the greenhouse effect appears to be small. The recreational and medical uses of N2O gradually diverged over time. N2O has analgesic and anesthetic effects, making it widely used in modern dentistry and surgery. New research has also begun studying N2O's antidepressant actions. N-methyl-D-aspartate (NMDA) antagonism and opioid effects are believed to be the main underlying biochemical mechanisms. At this point, numerous questions remain open and, in particular, the conduct of larger clinical trials will be essential to confirm N2O's use as a rapid-acting antidepressant. The N2O concentration delivered, the duration of a single inhalation, as well as the number of inhalations ultimately required, deserve to be better understood. Finally, the non-medical use of N2O has gained significant attention in recent years. Sudden deaths directly attributed to N2O are primarily due to asphyxia. Heavy, chronic N2O use may result in vitamin B12 deficiency, which, among other things, may cause megaloblastic anemia, venous thrombosis, myeloneuropathy, and skin pigmentation. Helpful biochemical tests include homocysteine and methylmalonic acid. The centerpiece of treatment is complete cessation of N2O use together with parenteral administration of vitamin B12.

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