The boon and bane of nitrous oxide.

Nitrous oxide (N2O) has been used since the 1700s and today is a significant greenhouse gas and ozone-depleting substance, though medical use contributes little to these effects. Its analgesic and anesthetic properties make it common in dentistry and surgery, and new research suggests antidepressant actions through NMDA antagonism and opioid effects. Larger clinical trials are needed to confirm its use as a rapid-acting antidepressant, and optimal dosing and duration remain unclear. Non-medical use has increased, with risks including asphyxia from acute use and vitamin B12 deficiency from chronic use, leading to conditions like megaloblastic anemia, venous thrombosis, myeloneuropathy, and skin pigmentation. Treatment requires stopping N2O use and administering parenteral vitamin B12; homocysteine and methylmalonic acid are helpful diagnostic tests.

Study at a glance

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.