It is somewhat surprising that nobody has thought to treat an illness where the main symptom is profound sadness with a substance that makes people laugh. Such was the sentiment expressed by the head of a team that conducted a small pilot study that found nitrous oxide – commonly known as laughing gas – shows promise in alleviating severe depression that is not responding to treatment.

Share on Pinterest Researchers behind a new pilot study suggest laughing gas may offer temporary relief from symptoms while patients with depression wait for longer term treatment to show results.

The team, from Washington University School of Medicine in St. Louis, MO, reports the findings of their proof-of-concept study into the effects of laughing gas on severe, treatment-resistant depression in the journal Biological Psychiatry.

They believe it is the first study where patients with depression have been given nitrous oxide or laughing gas, a fact that lead researcher Peter Nagele, assistant professor of anesthesiology, remarks on:

“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.”

The study involved 20 patients with severe depression whose illness was not responding to conventional treatment.

It was a randomized, placebo-controlled crossover trial where the participants underwent two treatments: once with the active drug – the laughing gas or nitrous oxide – and once with a placebo, on separate occasions. They were randomly assigned to receive either the drug or the placebo first.

The active drug was a mixture of half oxygen and half nitrous oxide – the same mixture that dentists give to patients as a sedative agent. The placebo was a mixture of oxygen and nitrogen, the two main gases in the air we breathe.

Symptom severity was evaluated shortly after the treatments, and then on the day after. This was by means of a survey that examined items like sadness, feelings of guilt, suicidal thoughts, anxiety and insomnia.