US News: A groundbreaking analysis of global clinical trials suggests that nitrous oxide, commonly known as laughing gas, can deliver rapid improvements in symptoms for people with hard-to-treat depression, often within hours of a single supervised session.
Researchers at the University of Birmingham, working with colleagues from the University of Oxford and Birmingham and Solihull Mental Health NHS Foundation Trust, reviewed seven completed trials and four ongoing study protocols involving hundreds of patients worldwide. Their findings, published November 30 in the journal eBioMedicine, highlight how a medically administered dose of 50 percent nitrous oxide can significantly ease depressive symptoms in adults facing major depressive disorder or treatment-resistant cases where standard antidepressants provide little or no benefit.
In pooled data from three trials using that specific concentration for one session, patients experienced an average drop of about 2.7 points on validated depression rating scales as early as two hours after treatment, with meaningful relief still evident 24 hours later. One smaller study of 20 individuals with stubborn depression found that 20 percent responded positively to the gas compared with just 5 percent on placebo, and 15 percent achieved full remission.
Nitrous oxide has long been a safe staple in dentistry and obstetrics for pain management and sedation, thanks to its quick action and rapid clearance from the body. Scientists believe its antidepressant effects stem from influencing glutamate pathways in the brain, similar to the mechanism behind ketamine, another emerging rapid-treatment option.
While a single inhalation often produced noticeable short-term gains, those benefits typically faded within a week. Repeated sessions over several weeks, however, appeared to extend the improvements, pointing toward a potential role for ongoing maintenance dosing.
“Depression can be utterly debilitating, especially when conventional antidepressants fail for nearly half of patients,” said Kiranpreet Gill, the study’s first author and a PhD researcher at the University of Birmingham. “By compiling the strongest available evidence, we’ve shown that nitrous oxide holds real potential for delivering fast, clinically meaningful relief in severe cases.”
Side effects were generally mild and transient, including headaches, nausea, or dizziness that resolved quickly without medical intervention. The review raised no major safety concerns for short-term use at the studied concentrations, though researchers stressed the importance of careful monitoring.
Senior author Professor Steven Marwaha described the work as an important advance for patients who have exhausted other options. “This represents a key step forward in identifying nitrous oxide as a viable additional tool for those whose depression hasn’t responded to existing therapies,” he said.
Encouraged by the results, the team is now preparing the United Kingdom’s first National Health Service trial dedicated to evaluating nitrous oxide as a practical treatment for major depression in real-world clinical settings.
Experts note that while these early signals are encouraging, larger and longer studies are needed to confirm durability, optimal protocols, and how the gas might fit alongside or complement other rapid-acting interventions. For millions struggling with depression that defies traditional pills, however, the prospect of relief measured in hours rather than weeks offers fresh hope from an unexpectedly familiar source.
