Researchers at The Alfred Hospital in Melbourne are looking to explore the benefits of laughing gas as a treatment for depression. Participants are currently being invited to enrol for an Australia-first medical trial, where they’ll be administered multiple doses of nitrous oxide in a controlled clinical environment, in the hope that the drug might target a different type of neural pathway to more common antidepressant medication and help alleviate the symptoms of those suffering from treatment-resistant depression.

Associate Professor Paul Myles, who’s leading the study, described it as "a really exciting trial because we already know nitrous oxide is safe to use and has few side effects." Participants will inhale nitrous for a full hour at a time, once a week for a total of four weeks. "A patient can effectively come in and sit in a chair and relax and listen to nice music and breathe in the gas and they'll start to feel, perhaps, slightly woozy and a bit better in their mood almost immediately,” Paul told Fairfax—a description that will surely resonate with anyone who’s ever huffed nangs. “Then literally half an hour later they can go home."

Although nitrous leaves the body fairly quickly after inhalation, early indications reportedly show that the positive effects of the gas and its influence on a person’s mood can last up to a week. For that reason, Paul’s hoping nitrous could be used as a quick-fix treatment to “bridge the gap” while patients wait days or weeks for their other antidepressant medications to kick in. For people with severe depression who are at serious risk of suicide, that could make a big difference. But researchers also believe that laughing gas could be an effective alternative for people who are resistant to more traditional forms of medication.

“Different types of depression affect different areas of the brain, so treatment is not a one size fits all approach,” said Jayashri Kulkarni, director of the Monash Alfred Psychiatry Research Centre. “Traditional medication is not effective for some people.”

Speaking to Fairfax, Paul expanded on this idea. “The reason why we think laughing gas is very likely to be so effective is that it works through completely different pathways in the brain to all the normal antidepressant medications," he said. "All the ones that have been used in the last 50 or so years have worked through what’s known as the serotonin pathway. This works through a different pathway which we call the NMDA pathway.”

The research at The Alfred will follow in the steps of similar studies overseas—in particular, a breakthrough University of Washington pilot study from 2014 which found that two-thirds of participants experienced an improvement in depression symptoms after being treated with laughing gas. Seven patients reported mild improvement in their symptoms a day after the treatment; another seven reported significant improvement; and three reported that their symptoms had disappeared almost completely. No patients said their symptoms had worsened after inhaling nitrous oxide.

“Our findings need to be replicated… we believe therapy with nitrous oxide eventually could help many people with depression,” said principal investigator Peter Nagele, MD, assistant professor of anesthesiology at the School of Medicine. “It’s kind of surprising that no one ever thought about using a drug that makes people laugh as a treatment for patients whose main symptom is that they’re so very sad.”

Participants in The Alfred trial must have a history of clinical depression and be currently on medication, over the age of 18, able to give informed consent, and not acutely suicidal.

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