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11th Jun 2021

Low doses of laughing gas could help treat depression, study suggests

Charlie Herbert

The new study expanded on research that had been done in 2014 on the benefits of nitrous oxide.

A new study has suggested that nitrous oxide, which is more commonly known as laughing gas, could be effective for rapidly relieving treatment-resistant depression.

The small study was conducted by the University of Chicago Medicine and Washington University, and was published on June 9 in the Science Translational Medicine Journal.

The trial involved 24 participants and expanded in a previous trial from 2014 which found that inhaling 50% nitrous oxide – the usual amount of gas that would be given as pain relief during surgery – could reduce symptoms of depression that can be resistant to other treatments such as antidepressants.

The 2014 study found that benefits of the gas did not last for more than a week. However, this new study concluded that in lower doses, the effects of laughing gas to treat depression could last for several weeks.

The study’s co-author Peter Nagele said that the gas works the same way as ketamine therapy (yes, that’s a thing) and nasal sprays. These all work by blocking molecules on nerve cells called N-methyl-D-aspartate (NMDA) receptors.

In a press release Nagele said: “This investigation was motivated by observations from research on ketamine and depression.

“We wondered if our past concentration of 50% had been too high. Maybe by lowering the dose, we could find the ‘Goldilocks spot’ that would maximise clinical benefit and minimise negative side effects.”

During the trial, 24 participants dealing with treatment-resistant depression were randomly assigned three different treatments over a period of three months, with a one-month gap between each treatment. The first treatment administered was an hour-long high dose of nitrous oxide at 50%; the second was an hour-long low dose of the drug at 25%; while the last was a placebo mixture of oxygen and air.

The research found that two weeks later, those who had been given the laughing gas showed more long-term benefits than those who had been given the placebo. The higher dose though was linked to four times more side effects such as nausea.

The study said: “These results highlight that lower concentrations of nitrous oxide may be a useful treatment for treatment-resistant major depression.”

For a variety of reasons, experts are keen to stress that the findings are far from conclusive. One of the key limitations of the trial is the fact that it involved so few participants.

Nagele is clear about what the next stage will be though.

“These have just been pilot studies,” he said. “But we need acceptance by the larger medical community for this to become a treatment that’s actually available to patients in the real world. Most psychiatrists are not familiar with nitrous oxide or how to administer it, so we’ll have to show the community how to deliver this treatment safely and effectively.”