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Inhaled Nitrous Oxide Shows Rapid Benefits for Treatment‑Resistant Depression, Review Finds

Researchers reviewing clinical evidence report that a single inhaled dose of medical‑grade nitrous oxide (50% concentration) produced rapid reductions in depressive symptoms within 24 hours, though benefits often did not last a week. Repeated treatments over several weeks appeared to give more sustained improvement. The gas likely acts on glutamate receptors in a manner similar to ketamine. Larger, controlled trials—including a planned NHS study—are needed to confirm efficacy, optimal dosing, and safety.

04:42 PM, 12/01/2025Health
Inhaled Nitrous Oxide Shows Rapid Benefits for Treatment‑Resistant Depression, Review Finds

New analysis led by researchers at the University of Birmingham and published in eBioMedicine indicates that medically administered inhaled nitrous oxide can produce rapid—but often short‑lived—improvement in depressive symptoms for adults with major depressive disorder who have not responded to standard antidepressants.

Key findings

Across three clinical trials, a single inhaled dose of medical‑grade nitrous oxide at a 50% concentration produced a measurable and significant reduction in depressive symptoms within 24 hours. Those improvements generally did not persist for a full week after a single treatment. However, repeated administrations over several weeks appeared to deliver more durable benefits, suggesting that multiple sessions may be necessary to achieve sustained clinical improvement.

Possible mechanism

Nitrous oxide is believed to act on the brain’s glutamate system in a way similar to ketamine, a fast‑acting antidepressant used in clinical settings. This glutamatergic action may underlie the rapid onset of symptom relief observed in the trials.

Limitations and safety

The available evidence is limited: only a small number of trials were included, and they used differing methods to measure and report depressive symptoms, which increases variability in the results. The review also found that the likelihood of adverse effects rose at concentrations above 50%.

Next steps

To address these uncertainties, researchers are preparing a randomized trial within England’s National Health Service (NHS) to evaluate whether nitrous oxide can be a viable long‑term treatment option and how it might be integrated into routine care. Future studies will need to define optimal dosing, treatment frequency, durability of benefit, and long‑term safety.

Bottom line: Inhaled nitrous oxide shows promising rapid antidepressant effects for people with treatment‑resistant depression, but more rigorous, larger trials are required before it can be recommended as a routine long‑term treatment.

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