Laughing Gas:  A New Treatment for Depression?

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It seems so obvious when you stop to think about it.  Why wouldn’t researchers consider laughing gas to help treat someone who is sad?   Perhaps it’s because laughing gas (nitrous oxide) has been used primarily as an anesthetic in dental offices for approximately 150 years.  With nearly one-third of depressed patients not responding to traditional antidepressant medication, this discovery seems long overdue. The study, conducted at the Washington University School of Medicine in St. Louis, is believed to be the first research in which patients with depression were given laughing gas.

The Study

Although the trial was small, it shows a lot of promise. Of the 20 treatment-resistant, clinically depressed patients who participated in the study, two-thirds felt an improvement in their symptoms after receiving the nitrous oxide (N2O). One-third of the same patients, who received a placebo, reported improved symptoms after treatment.

The Results

Two hours after each treatment and again the next day, participants were asked about the severity of their symptoms, such as sadness, feelings of guilt, suicidal thoughts, anxiety and insomnia. One day after N2O treatment, seven patients reported mild improvement, and seven reported significant improvement and three patients reported that their depressed symptoms had disappeared almost completely. No patients said their symptoms worsened after treatment with nitrous oxide.

Although the gas rapidly leaves the body upon removal, making it an optimal anesthetic, researchers feel that the reported benefit is a real effect – not a side effect of the N2O treatment. Further, they noted that some patients experienced improvements, which lasted for at least one week after the N2O exposure.

Peter Nagele, MD, principal investigator and assistant professor of anesthesiology at the School of Medicine explained, "Our findings need to be replicated, but we think this is a good starting point, and we believe therapy with nitrous oxide eventually could help many people with depression.”   He went on to explain that "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,".

What Do I Think?

And I agree. It seems a little obvious that an agent has been around for so long, but has never been truly tested in this population of people. Having had a dental procedure or two in my lifetime, I can only speak to the positive feelings or relaxation and euphoria that laughing gas brings.  Nitrous oxide was originally discovered in 1772 by an English chemist by the name of Joseph Priestley. Nitrous oxide is also called Di-Nitrogen Monoxide, or Laughing Gas, and is one of several oxides of nitrogen. It is a colorless gas with a pleasant, sweetish odor and taste, which is known to produce insensibility to pain preceded by mild hysteria, sometimes laughter when inhaled.  On a side note, the gas is also used as a propellant in food aerosols, and has been linked to teens that want to experience a quick high (called huffing). When administered properly, and in combination with oxygen, the deadly effects of N2O are mitigated.

Some years later, Humphrey Davy was credited for its usage as an anesthetic. He administered N2O on himself for a toothache and gum infection, explaining, “The pain always diminished after the first four or five inspirations; the thrilling came on as usual, and uneasiness was for a few minutes swallowed up in pleasure.”

With standard antidepressants and cognitive behavior therapy, both patients and their doctors often have to wait weeks before they know whether the treatment is even working or any benefits are noticeable to the patients.  However, when used clinically, laughing gas becomes an attractive therapy. The most common side effects are nausea and vomiting, and the gas leaves the body very quickly after people stop breathing it.  

"When they received nitrous oxide, many of the patients reported both rapid and significant improvement," said co-investigator Charles R. Conway, MD, associate professor of psychiatry. "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 type of rapid benefit is a far cry from Prozac, Zoloft, Lexapro and other selective serotonin reuptake inhibitors (SSRIs), whose benefits can take anywhere from two to four weeks before the first real symptom improvement shows up.  

"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," said co-investigator Charles F. Zorumski, MD, the Samuel B. Guzé Professor and head of the Department of Psychiatry and director of the Taylor Family Institute. "Or perhaps the drug could be used to relieve symptoms temporarily until more conventional treatments begin to work."  Because of the small population size of the study, researchers want to further investigate to potential benefits of N2O treatment. They also plan to test various concentrations of N2O to see how they may influence the symptoms of depression. Those studies will begin soon.  In the meantime, perhaps going to the dentist isn’t as bad as most of us have come to believe it is. In this case, laughter, or at least laughing gas, really may be the best medicine.

The findings were presented on December 9, 2014, at the annual meeting of the American College of Neuropsychopharmacology in Scottsdale, AZ. They were also published concurrently online in the journal Biological Psychiatry.

Conclusion:  Laughing gas may serve as a powerful fast-acting antidepressant for treatment-resistant depression.

- Laura Wells

Washington University in St. Louis. (2014, December 10). Laughing gas shows promise for severe depression, pilot study suggests. ScienceDaily. Retrieved December 11, 2014 from www.sciencedaily.com/releases/2014/12/141210074146.htm