Nitrous oxide, commonly known as “laughing gas,” may quickly ease symptoms of depression, a new study suggests.
The colourless gas, widely used as a painkiller, has shown fast-acting benefits in adults with major depressive disorder and treatment-resistant depression—cases where standard antidepressants have failed. Researchers say it could help the roughly 48% of patients who do not respond to first-line treatments.
Kiranpreet Gill, a PhD researcher at the University of Birmingham and first author of the study, said: “Depression is a debilitating illness, made worse by the fact that antidepressants make no meaningful difference for almost half of all patients. Our analyses show that nitrous oxide could form part of a new generation of rapid-acting treatments.”
The study, conducted by teams from the University of Birmingham, the University of Oxford, and Birmingham and Solihull Mental Health NHS Foundation Trust, reviewed seven clinical trials and four protocol papers from around the world. Researchers examined nitrous oxide’s effects on major depressive disorder, treatment-resistant depression, and the depressive phase of bipolar disorder.
Results showed that a single inhaled dose of 50% nitrous oxide produced rapid, significant reductions in depressive symptoms within 24 hours. Effects typically lasted less than a week, but repeated doses over several weeks extended the benefits.
Nitrous oxide is believed to act on glutamate receptors in the brain—key sites involved in learning and memory—similar to ketamine, another rapid-acting antidepressant. This may explain why mood can improve so quickly after inhalation.
Steven Marwaha, professor at the University of Birmingham and senior author of the study, said: “This is a significant milestone in understanding the potential of nitrous oxide as an added treatment for patients who have not benefited from current therapies. This population often loses hope of recovery, making these results particularly exciting.”
The study also assessed safety and side effects. Some patients experienced nausea, dizziness, or headaches, which were short-lived and resolved without medical intervention. Higher doses increased the likelihood of side effects, but no short-term safety concerns were reported. Researchers caution that long-term safety still needs investigation.
While recreational use of nitrous oxide was banned in 2023, it remains legal for medical purposes. Heavy recreational use can cause vitamin B12 deficiency, potentially damaging spinal nerves.
David Nutt, professor of neuropsychopharmacology at Imperial College London, told The Independent: “It’s called laughing gas because it removes natural tension and anxiety, allowing people to relax and feel happy instantly. It changes brain blood flow and likely disrupts the circuits involved in depression.”
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