Laughing gas a promising treatment for depression

Nitrous oxide, informally known as laughing gas, has shown rapid antidepressant effects in people with depression in a series of small clinical trials, with symptoms easing within hours of inhaling it. The treatment involves breathing in a mix of nitrous oxide and oxygen for up to an hour.

“Nitrous oxide is a promising rapid-acting treatment for depressive disorders. It has the potential to form part of a new generation of rapid-acting treatments for depression,” Angharad de Cates, from the University of Birmingham, told New Atlas.

The team led by Kiranpreet Gill reviewed the data from seven clinical studies involving 247 adults with major depressive disorder, treatment-resistant depression, or bipolar depression. These studies were published between 2015 and 2025, and tested nitrous oxide at concentrations of 25% or 50%.

In the review, Gill and her colleagues found that a single treatment of inhaling clinical nitrous oxide at 50% concentration produced rapid and noticeable reductions in depressive symptoms at both two hours and 24 hours after treatment. However, the benefits did not last for long and faded within one week.

From these pooled results, de Cates concluded, “The absence of sustained benefit at 1 week implies that a single administration is not sufficient for longer-lasting remission.”

The scientist told New Atlas that repeated dosing over several weeks led to more durable improvements, suggesting multiple treatment sessions (compared to a single dose) may be required to maintain clinical benefit in the medium term.

But how does nitrous oxide actually treat depression?

Glutamate is a key messenger chemical in the brain, de Cates told New Atlas, involved in emotional regulation, which is often disrupted in the case of depression. Changing how the glutamate system works in the brain can restore healthier communications between brain cells.

Nitrous oxide resets the chemical signals by blocking a type of receptor – known as the NMDA receptor – that regulates glutamate. The gas also boosts the blood flow in the brain, improving oxygen and nutrient delivery to support brain function. Finally, nitrous oxide may quiet the brain’s default mode network – a set of connected brain regions that, when overactive, is linked to rumination and repetitive self-critical thoughts. Reducing activity here may help break cycles of negative thinking that are common in depression.

The study also highlights ketamine, a glutamate-modulating agent, showing rapid antidepressant effects. However, the researchers suggest nitrous oxide as a more practical, lower-intensity alternative to ketamine.

“Compared to ketamine, nitrous oxide may produce less severe adverse effects, and it requires less monitoring after each administration,” de Cates told New Atlas. “However, its use is still in the research phase, and at this time it is not ready to replace ketamine in routine clinical use.”

The study ultimately calls for further research to understand how this approach can best support people living with severe depression who don’t respond to conventional interventions.

The study was published in the journal eBioMedicine.

Source: University of Birmingham