Therapeutic Efficacy and Neurobiological Mechanisms of Nitrous Oxide in Treatment-Resistant Depression
Journal of Pharma Insights and Research December 5, 2025 Syed Ansar, S. Ahmed, Aishvarya Baburao Ghayale et al.
A single inhalation session of nitrous oxide can produce rapid antidepressant effects that last well beyond the gas's elimination from the body. Sub-anesthetic concentrations, specifically 25%, maintain antidepressant efficacy while minimizing adverse effects like nausea and dissociation. The mechanism involves NMDA receptor antagonism, interaction with the endogenous opioid system, GABAergic disinhibition, and downstream neuroplasticity signaling including BDNF release. Current research focuses on optimal dosing protocols, managing risks from vitamin B12 oxidation, and assessing nitrous oxide's feasibility as an office-based intervention.