Laughing gas - new trick to fight depression

Recent clinical studies reveal nitrous oxide (N₂O), commonly known as "laughing gas," may offer breakthrough potential in treating treatment-resistant depression (TRD). A 2023 Phase II trial by Washington University School of Medicine demonstrated that a single one-hour inhalation of 50% N₂O/oxygen blend provided rapid antidepressant effects lasting 24 hours to 1 week in 65% of participants, comparable to ketamine but with shorter-acting properties.

The mechanism appears linked to N₂O's NMDA receptor antagonism – modulating glutamate signaling similarly to ketamine – while concurrently stimulating opioid and GABA pathways. This multimodal action may explain its unique ability to disrupt depressive neural circuits while minimizing dissociation risks.

Current Phase III trials are exploring optimized dosing regimens (e.g., 3x monthly inhalations). While not yet FDA-approved, N₂O therapy could become a bridge intervention for suicidal crisis management.