“Laughing Gas” Shows Promise as Rapid-Acting Treatment for Depression, Study Finds
A new meta-analysis suggests nitrous oxide, commonly known as “laughing gas,” could offer a swift path to relief for individuals battling major depressive disorder, particularly those unresponsive to traditional antidepressants.
A team led by Professor Steven Mawaha at the University of Birmingham in the UK published findings in the medical journal eBioMedicine on December 1st, 2025, detailing a comprehensive review of seven clinical trials and four protocol papers. The research confirms a short-term therapeutic effect of nitrous oxide in patients with major depressive disorder (MDD), including those with treatment-resistant depression (TRD).
The study represents what researchers call the most reliable evaluation to date of clinically administered nitrous oxide’s ability to rapidly alleviate depressive symptoms. This is particularly significant given that nearly half – approximately 48% – of depression patients in the UK are classified as having TRD, a condition where symptoms persist despite trying two different types of antidepressants.
Researchers investigated the use of nitrous oxide – already utilized for pain relief and anxiety reduction in dental procedures – across a spectrum of depressive disorders, including MDD, TRD, and even bipolar depression. Clinical trials demonstrated that a single administration of 50% nitrous oxide resulted in a rapid and substantial reduction in depressive symptoms within 24 hours. However, this initial improvement was not sustained beyond one week.
Interestingly, repeated administrations of nitrous oxide over several weeks yielded a more prolonged positive effect. This suggests that, unlike a one-time intervention, multiple treatments may be necessary to maintain clinical benefits. Safety assessments revealed minor side effects like nausea, dizziness, and headaches, all of which resolved quickly without requiring medical intervention.
The mechanism behind nitrous oxide’s potential antidepressant effect is believed to mirror that of ketamine, another fast-acting antidepressant. Both substances are thought to act on glutamate receptors in the brain, potentially explaining the immediate mood-boosting effects.
“Depression is a very debilitating disease, and antidepressants are effective in only half of patients, making treatment more difficult,” stated a lead researcher involved in the study. “This study suggests that nitrous oxide can be used as a quick-acting treatment for depression.”
Despite these promising results, the research team cautions that the limited number of clinical trials necessitates further investigation. Additional studies are needed to determine the optimal dosage, assess long-term safety, and explore how nitrous oxide can be effectively integrated with existing treatment protocols.
Professor Mawaha emphasized the importance of this work, stating, “This study is an important milestone in understanding the potential of nitrous oxide as an additional treatment option for patients with depression who have failed conventional treatment. These results are particularly encouraging as this group of patients often lose hope for recovery.”
The full study, “Nitrous oxide for the treatment of depression: A systematic review and meta-analysis,” by Kiranpreet Gill et al., is available at http://dx.doi.org/10.1016/j.ebiom.2025.106023.
