The analysis, published in the journal eBioMedicine, examined evidence from a series of studies that tested medically supervised nitrous oxide in adults diagnosed with major depressive disorder and treatment resistant depression. Almost half of patients in the UK fall into the treatment resistant category, meaning they do not improve after trying at least two different antidepressant medications.
Researchers from the universities of Birmingham and Oxford, working with Birmingham and Solihull Mental Health NHS Foundation Trust, reviewed seven clinical trials involving nitrous oxide, which is already used in medical settings as a pain reliever. The studies covered patients with major depressive disorder, treatment resistant depression and bipolar depression.
The team found that a single session of inhaling nitrous oxide at a concentration of fifty per cent delivered rapid and meaningful reductions in depressive symptoms within twenty four hours. These improvements, however, typically faded within a week.
Further research showed that repeated sessions over several weeks produced longer lasting benefits, suggesting that continuous dosing may be necessary to maintain improvement.
Nitrous oxide is believed to affect glutamate receptors in the brain, which help regulate communication between brain cells. These circuits are strongly linked to mood control and emotional stability.
Kiranpreet Gill, a doctoral researcher at the University of Birmingham and the study’s lead author, said the findings offer strong evidence that nitrous oxide can deliver fast and clinically significant short term relief for people experiencing severe depression. She added that the gas could become part of a new generation of rapid acting treatments.
Researchers also assessed safety. Some patients reported temporary side effects, including nausea, dizziness and headaches. All symptoms resolved without treatment, and no serious short term safety concerns were identified.
Gill cautioned that more research is required to determine the best dose, the long term safety profile and how the treatment should be used in practice.
Professor Steven Marwaha, senior author of the study, said the findings mark an important step in assessing nitrous oxide as an additional treatment option for people whose symptoms have not responded to current therapies.
Independent experts urged caution. Professor Hamish McAllister Williams of Newcastle University noted that although the review is comprehensive, the evidence remains limited. He pointed out that the trials were small, varied widely in design and duration, and included different types of patients. He also warned that many participants could tell whether they had been given nitrous oxide or a placebo, which may have influenced the results.
He said the review supports further investigation, but stressed that larger and better controlled trials are needed before firm conclusions can be drawn.
Nitrous oxide has also become a common recreational substance, often sourced from whipped cream cartridges. Doctors have reported a rise in patients with nerve damage, bladder issues and blood related complications linked to heavy use. It is now the second most commonly used drug among people aged sixteen to twenty four, behind cannabis.
