A proof-of-concept trial has shown that nitrous oxide, or laughing gas, holds potential as an effective treatment for severe depression in patients who don't respond to standard therapies. Laughter may indeed be the best medicine.

The study, which was conducted at Washington University in St. Louis, is the first to consider the effects of laughing gas on depressed patients, which is quite surprising when you think about it. Why not use a drug that makes people laugh, particularly if they're super sad?

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This actually reminds me of laughter yoga, the practice of prolonged voluntary laughter. The basic idea is that forced laughter has the same physiological and psychological benefits as spontaneous laughter. Indeed, laughing — whether it be voluntary or involuntary — has been shown to confer a number of medically beneficial effects, including boosts to cardiovascular health and mood. Laughter has even been shown to increase a person's pain threshold.

A Laughing Matter

For the new study, 20 patients with treatment-resistant depression (TRD) were treated twice with laughing gas over a 24-hour period. It's a very small sample size, and the duration of the study was unreasonably short, but the researchers are nonetheless encouraged by the results. To be fair, the study was a quick pilot project to see if this line of inquiry is worth pursuing, which appears to be the case.

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The findings showed that two-thirds of the patients who received laughing gas experienced an improvement in symptoms such as sadness, feelings of guilt, suicidal thoughts, anxiety, and insomnia. By comparison, one-third of the same patients reported improved treatments after receiving a placebo (a mixture of oxygen and nitrogen, which is basically air). In terms of specifics, seven reported mild improvements, while another seven reported that they felt significantly better.

Importantly, because nitrous oxide leaves the body at a rapid rate after inhalation, the researchers evaluated the moods of the patients the following day. Consequently, they believe that the benefits were real and not just a side effect of the nitrous oxide.

"When they received nitrous oxide, many of the patients reported a rapid and significant improvement," said co-investigator Charles R. Conway in a release. "Although some patients also reported feeling better after breathing the placebo gas, it was clear that the overall pattern observed was that nitrous oxide improved depression above and beyond the placebo. Most patients who improved reported that they felt better only two hours after treatment with nitrous oxide. That compares with at least two weeks for typical oral antidepressants to exert their beneficial, antidepressant effects."

This is definitely good news when you consider that a third of all clinically depressed people suffer from TRD. It appears to be a quick-acting intervention, and with few side effects, the most common being nausea and vomiting.

Moving forward, the researchers are planning to conduct more thorough investigations, along with tests of various concentrations of laughing gas to see how each influences depression.

Read the entire study at Biological Psychiatry: "Nitrous Oxide for Treatment-Resistant Major Depression: a Proof-of-Concept Trial".

Top illustration: Doctor and Mrs Syntax, with a party of friends, experimenting with laughing gas. Coloured aquatint by T. Rowlandson after W. Combe. CC.

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