A common anesthetic gas, often called laughing gas, might offer quick relief from depressive symptoms, according to a new analysis of clinical studies published in eBioMedicine.
Nitrous oxide, or N2O, is already widely used in dentistry and medicine for pain relief and sedation. Now, researchers are exploring its potential as a fast-acting antidepressant, especially for people whose symptoms don’t improve with standard medications like selective serotonin reuptake inhibitors.
Depression affects hundreds of millions of people worldwide, causing deep sadness, loss of interest in life, and sometimes thoughts of suicide. Traditional antidepressants can take weeks to start working and don’t help everyone—up to half of patients see little or no benefit, leading to what’s known as treatment-resistant depression.
That’s where nitrous oxide comes in. It works by blocking certain signals in the brain involved in mood regulation, similar to how the drug ketamine provides rapid relief but through a gentler mechanism. In medical settings, it’s inhaled mixed with oxygen, usually for about an hour per session.
The new review, led by scientists at the University of Birmingham, pooled data from seven small clinical trials involving about 250 adults with major depression or treatment-resistant forms of the illness. Most studies tested a single dose of nitrous oxide at 25% or 50% concentration, compared to inhaling plain air, oxygen, or a mild sedative as a placebo.
Across the trials, people breathing nitrous oxide saw noticeable drops in depression symptoms—like feeling less hopeless or exhausted—within just two hours, with effects peaking around 24 hours later. On average, symptom scores fell by about three to five points on standard rating scales at that early mark. But for single sessions, the benefits often faded after a week.
A couple of studies tried repeated doses, giving nitrous oxide once or twice a week for up to a month. Those showed more lasting improvements, with some participants achieving full remission—meaning their symptoms essentially disappeared. Response rates hit as high as 90% in one trial, compared to much lower in placebo groups.
“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,” said Kiranpreet Gill, a PhD researcher at the University of Birmingham and first author of the study. “This study brings together the best possible evidence indicating that nitrous oxide has the potential to provide swift and clinically significant short-term improvements in patients with severe depression.”
The gas was generally safe, with side effects like nausea, dizziness, or headache that were mild and went away quickly without treatment. Higher doses led to more of these issues, but nothing serious cropped up in the short term. Researchers noted that longer studies are needed to check for any risks over time, especially since recreational use of high-purity nitrous oxide can cause problems like nerve damage if overdone.
Experts say this could open doors for people stuck in cycles of ineffective treatments. “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,” said Professor Steven Marwaha from the University of Birmingham, a psychiatrist and senior author of the study.
Still, the evidence comes from early, small trials, and bigger ones are underway to test optimal dosing, how long effects last, and how to combine it with other therapies. One ongoing study aims to see if nitrous oxide helps older adults with depression and thinking problems, while another looks at its role in easing suicidal thoughts.
If confirmed, nitrous oxide could become a simple, in-clinic option—easy to administer without needles or refrigeration, potentially making it more accessible than some current rapid treatments.
Citations: eBioMedicine. DOI: 10.1016/j.ebiom.2025.106023
