Nitrous oxide, or ‘laughing gas’, could quickly ease depression symptoms, a new study suggests.
The colourless gas, inhaled and widely used as a painkiller, has shown fast-acting benefits in adults with major depressive disorder (long-lasting, severe depression) and treatment-resistant depression, where patients have not responded to standard treatments.
Researchers say it could be especially helpful for the 48 per cent who have not responded to first-line antidepressants.
Kiranpreet Gill, a PhD researcher funded by the Medical Research Council at the University of Birmingham and first author of the study, said: “Depression is a debilitating illness, made even more so by the fact that antidepressants make no meaningful difference for almost half of all patients diagnosed with it.
“Our analyses show that nitrous oxide could form part of a new generation of rapid-acting treatments for depression.”
The study, by teams from the University of Birmingham, the University of Oxford, and Birmingham and Solihull Mental Health NHS Foundation Trust, assessed seven clinical trials and four protocol papers from investigators worldwide.
Each study examined nitrous oxide for depressive disorders, including major depressive disorder, treatment-resistant depression and bipolar depression (the depressive phase of bipolar disorder).
Researchers found that a single treatment of inhaled clinical nitrous oxide at 50 per cent concentration produced rapid, significant reductions in depressive symptoms within 24 hours, though effects generally did not last beyond a week.
When doses were spaced over several weeks, the benefits lasted longer.
The drug is thought to act on glutamate receptors in the brain (key chemical signalling sites involved in learning and memory), in a similar way to ketamine, another rapid-acting antidepressant.
Researchers say this may explain why mood can improve soon 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 option for patients with depression who have been failed by current treatments.
“This population has often lost hope of recovery, making the results of this study particularly exciting.”
Researchers also examined safety and side effects. Some patients experienced nausea, dizziness and headaches, which passed quickly and resolved without medical intervention.
Although higher doses at 50 per cent concentration increased the likelihood of these side effects, researchers reported no short-term safety concerns.
They said longer-term safety must be assessed in future studies.
The gas was banned for recreational use in 2023 but remains legal for medical use.
Heavy recreational use can lead to vitamin B12 deficiency, which can damage nerves in the spinal cord.
David Nutt, professor of neuropsychopharmacology at Imperial College London, who has written about the clinical value of the drug, told The Independent: “It’s called laughing gas because it removes the natural tension and anxiety we all have in our brains, so it allows people to become relaxed and happy instantly.
“It changes the brain blood flow and so probably disrupts the brain circuits of depression.”
