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This Is Not a Joke: Laughing Gas May Treat Depression

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Don't laugh -- well, maybe do laugh; researchers say there may be a new way to treat depression using nitrous oxide. And yes, that's the laughing gas you may know from visits to your dentist.

The fairly gentle general anesthetic sometimes used in dental surgery may be an effective and quick-results treatment option for severe depression for patients who aren't helped by usual therapies including antidepressant medications, researchers at Washington University in St. Louis suggest.

In a pilot study, WU researchers had patients undergo two rounds of treatment for depression, with one group getting inhaled placebos and another group getting the half-oxygen, half-nitrous oxide mixture used in dental procedures.

Two-thirds of the study participants to whom gas was administered reported substantial improvements in their depression symptoms, compared to just a third of participants in the control placebo group, the researchers reported in the journal Biological Psychiatry.

The symptoms were gauged two hours after the experiment sessions, a day later and then a week later.

"The nitrous oxide treatment improved [symptoms] above and beyond the placebo," says Dr. Peter Nagele, assistant professor of anesthesiology in the university's School of Medicine. "This was fairly rapid, so at two hours. But our primary endpoint when we measured everybody -- we asked the patients to come back the next day -- was sustained to a day."

Nagel says he was convinced to examine the anti-depression possibilities of nitrous oxide after reviewing previous studies on ketamine use as a depression treatment.

Ketamine is a much stronger kind of anesthesia administered to patients undergoing surgery to ensure they don't awaken during a medical procedure.

"Interestingly, katamine and nitrous oxide, or laughing gas, share several aspects of how they work in the brain, and one core affect site is called the NMDA receptor," says Nagele. "Both nitrous oxide and ketamine act on this mechanism."

NMDA receptors are neurotransmitters that facilitate memory and cognitive function, although exactly how ketamine or nitrous oxide change the receptors' action to combat depression is "the million dollar question," that will require further research, says Nagele.

Still, nitrous oxide might be the better research candidate as it is a much more benign drug that ketamine, he says.

And since it is inhaled, it would be easer to administer to people suffering depression than an intravenous course of ketamine.

Although more benign that ketamine, nitrous oxide is not without its side effects, the researchers said, including altering the body's metabolizing of vitamin B12, which is involved in nerve conduction, and the production of both red blood cells and folic acid, which could be an issue for women who are pregnant.

Still, they say, nitrous oxide might have a place as a treatment for depression under certain circumstances.

"If our findings can be replicated, a fast-acting drug like this might be particularly useful in patients with severe depression who may be at risk for suicide and who need help right away," says WU psychiatry department head Charles F. Zorumski.

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