Synopsis

Source of validity: Scientific
Rating (out of 5): 3

Nitrous oxide, commonly known as "laughing gas," has garnered scientific interest in recent years as a potential treatment for depression, particularly treatment-resistant depression. Several small-scale clinical studies have investigated its efficacy. In a notable double-blind, placebo-controlled trial published in 2015 in the journal Biological Psychiatry, 20 patients with treatment-resistant major depression received a single administration of nitrous oxide. The results indicated a significant reduction in depressive symptoms 24 hours post-inhalation compared to placebo. Follow-up studies have supported these findings, suggesting that nitrous oxide may exert rapid-acting antidepressant effects, similar in some respects to ketamine, another NMDA receptor antagonist.

The proposed mechanism involves modulation of glutamatergic neurotransmission via noncompetitive inhibition of NMDA receptors, which may help reset dysfunctional neural circuits implicated in depression. However, the body of evidence is still relatively limited, with most studies involving small sample sizes and short follow-up periods. Larger, longer-term studies are needed to better understand the efficacy, safety, and optimal dosing protocols for nitrous oxide in depression treatment. Nonetheless, the current scientific evidence justifies cautious optimism and continued research in this area, though nitrous oxide is not yet a mainstream or approved treatment for depression outside of research settings.

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