Talk about taking things literally, but it really seems like laughing gas or nitrous oxide, as it’s known by its chemical formula, can relieve chronic depression symptoms even in those cases where no other treatment seemed to render results. This is the first time that laughing gas was used as a potential treatment for depression. The findings – if replicated by other independent trials – could lead to a new class of treatments based on nitrous oxide. Because of its immediate effects, “laughing gas” pills could be used as a quick fix in critical situations when depression, followed by suicidal thoughts sink in.

Don’t laugh – it’s no joke

Laughing gas is used by recreational drug users (Photo: Christopher Pledger)

Researchers at Washington University School of Medicine in St. Louis formed a group made up of 20 patients who had treatment-resistant clinical depression. The team performed two sessions: in the first one a gas mixture that was half oxygen and half nitrous oxide – the same mixture dentists give to patients undergoing dental procedures – was inhaled by the subjects, while in the second session the patients received a placebo mixture of oxygen and nitrogen, the two main gases in the air we breathe.

Two hours following each treatment and again the next day, the researchers surveyed the patients’ mood and the severity of their symptoms, such as sadness, feelings of guilt, suicidal thoughts, anxiety, and insomnia. Following the laughing gas session, two-thirds experienced an improvement in symptoms, compared to only one-third in the placebo session. Despite the small sample size, the findings do seem very promising.

“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,” said principal investigator Peter Nagele, M.D., assistant professor of anesthesiology.

What’s appealing about nitrous oxide is that its anti-depression effects were fast acting, as many participants reported  a rapid and significant improvement. Typically, an oral antidepressant needs a few weeks to work its magic and for patients to feel any improvement.

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Don’t expect laughing gas to replace Prozac any time soon. A lot more work needs to be done, like replicating the results, increasing the sample size and using different nitrous oxide concentrations.

“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.”

The paper, published in Biological Psychiatry, doesn’t try to explain how the laughing gas combats the symptoms. It might be a good idea to start from the obvious: laughter.

Quite possibly, the most offensive laughing gas ad ever.

Nitrous oxide enters the blood by diffusion from the alveoli whilst it is being inhaled, but does not bind with haemoglobin. It is fat soluble so quickly moves into cells, including synapse ends in the brain.Once in the brain, N2O induces “inconsistent changes in the basal levels of thalamic nuclei”, NMDA receptors in the brain whilst simultaneously encouraging the stimulation of the parasympathetic GABA receptors. This ultimately produces an anesthetic effect, which is no surprise since the compound has been extensively used in medicine and dentistry.

Concerning N2O’s euphoria or “good feeling” effects, the neural mechanisms are poorly understood – in essence, it’s this effect that might help people cope with their depression and loosen up a bit. Scientists should first understand the side effects in full, though. These include nausea and vomiting, but long term exposure is to the gas is poorly understood.

Nitrious oxide isn’t all laughs though. It’s the third most important greenhouse gas contributing to global warming after carbon dioxide and methane. Molecule for molecule, nitrous oxide is 300 times more potent in warming up the Earth than C02.