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As measured by the 21-item Hamilton Depression Rating Scale (HDRS-21), depression symptoms improved significantly more at 2 h and 24 h after receiving nitrous oxide than after placebo (mean difference of HDRS-21: ?4.8 points at 2 h, p=0.002, and ?5.5 points at 24 h, pGDC973 HDRS-21), and three patients (15%) reported a full remission (��7 points on the HDRS-21) after nitrous oxide inhalation. The results indicate a sustained antidepressant effect of Natural Product Library nitrous oxide. No serious adverse events occurred; all adverse events were brief and mild. Importantly, nitrous oxide did not cause psychotomimetic effects, such as hallucinations and delusions, which commonly occur after the administration of ketamine, the other NMDA receptor antagonist in clinical use. This study suggests that nitrous oxide has a rapid and sustained antidepressant effect in patients with treatment-resistant major depression, although further studies using a larger sample size are needed. Nitrous oxide is a colorless, non-flammable gas with a slightly sweet odor and taste and is also known as ��laughing gas�� because it can cause euphoric effects, including laughter, in humans. Nitrous oxide is also a drug of abuse, and its abuse potential represents a possible limitation for its Aldosterone utility in clinical psychiatry.5) Although nitrous oxide had been used in surgery and dentistry for its anesthetic and analgesic effects, this was gradually eliminated due to its neurotoxic side effects. More recently, nitrous oxide-induced neurotoxicity has been implicated in the development of long-lasting cognitive deficits when administered in very young or very old patients.6) Exposure to nitrous oxide during surgery is also widely known to elevate homocysteine levels in many patients.6) This likely results from nitrous oxide��s inactivation of methionine synthase, which generates methyl groups (via the active intermediary, S-adenosylmethionine) for the synthesis of DNA, RNA, myelin, and catecholamines, among other products. Elevated homocysteine after nitrous oxide inhalation is likely associated with neuronal death and subsequent cognitive decline. The precise mechanisms by which nitrous oxide exerts its antidepressant effect have not been fully elucidated. The predominant pharmacological effect of nitrous oxide is non-competitive inhibition of the NMDA receptor.6,7) Both 50% nitrous oxide and 0.
