Published on
Nitrous oxide – better known as “laughing gas” – could offer fast, short-term relief for people living with severe or treatment-resistant depression, according to a major analysis led by the University of Birmingham in the United Kingdom.
The review brings together the most robust clinical data available so far on how medically administered nitrous oxide (N₂O) affects adults with major depressive disorder (MDD) and treatment-resistant depression (TRD).
TRD is typically diagnosed when two standard antidepressants fail to make a meaningful difference – a situation affecting nearly half of UK patients, previous research shows.
Although nitrous oxide has long been used as a form of pain relief in medical settings, several small studies have explored its potential as a rapid-acting antidepressant.
Rapid improvements – but a need for repeated doses
The analysis, published in eBioMedicine, found that a single session of 50 per cent inhaled nitrous oxide produced significant reductions in depressive symptoms within 24 hours. However, these effects tended to fade within a week.
Repeated dosing, however, appeared to produce more sustained overall improvements. This mirrors what researchers have seen with ketamine, another fast-acting treatment thought to target similar glutamate pathways in the brain.
“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 report.
“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,” she said.
Nitrous oxide could form part of a “new generation of rapid-acting treatments,” she added, noting the need for larger trials to determine safe, repeatable dosing strategies.
More research on the long-term effects is needed
The study found that side effects such as nausea, dizziness and headaches were relatively common, particularly at higher doses, but generally brief.
No immediate safety concerns were reported.
Still, researchers caution that long-term effects remain largely unstudied and the small number of existing trials makes it difficult to draw firm conclusions.
The research forms part of work by the NIHR-funded Mental Health Mission Midlands Translational Centre, focusing on improving care for patients with severe and treatment-resistant depression.
Building on the growing evidence, the team is now preparing what would be the first National Health Service trial in the UK to assess whether nitrous oxide can be delivered safely and acceptably as a clinical treatment for major depression.