‘Laughing gas’ may help combat depression

by Alan Mozes
healthday reporter

Thursday, June 10, 2021 (Health Day News) — When antidepressant barely fail to rein in treatment depression, Normal anesthetic Most people know that “laughing gas” can be a safe and effective alternative, new research suggests.

Discovery deals with 28 patients battling “treatment-resistant” major depression“A serious condition that investigators say affects up to a third of all patients – an estimated 17 million American adults – who develop major depressive disorder.

For such patients, antidepressants often fail to provide relief. But after three one-hour laughing gas inhalation sessions spread over three months, 85% of patients had relief from significant depression, which persisted for weeks after treatment.

“Laughing gas is nitrous oxide, one of the oldest and most commonly used anesthetics,” explained study author Peter Nagel, MD, chair of Anesthesia and Critical Care at the University of Chicago.

“And we found that laughing gas, for example, at a much lower concentration than is used during dental procedures, can help patients with difficult-to-treat depression,” Nagel said.


Between 2016 and 2019, Nagel’s team tried two laughing gas formulations: one at 50% nitrous oxide levels and the other at 25% levels.

Previous investigations had already demonstrated an antidepressant benefit at high levels. But those efforts only assessed benefits 24 hours post-treatment. And patients exposed to high doses commonly experience side effects, including: Getting nausea, sedation and or “mild” Separation, “A kind of daydreaming experience.

In the latest study, the patients were between 18 and 75 years old. All were asked to continue their usual depression care and to maintain their current antidepressant regimen.

About one third were exposed to three sessions of 50% nitrous oxide inhalation treatment, one third were given 25% nitrous oxide inhalation treatment and one third were given oxygen inhalation treatment with no laughing gas.

Treatment was given through a standard anesthesia face mask, and all were monitored for one hour after treatment.

After four patients withdrew from the study, results were drawn from 20 patients who completed all three inhalation sessions and four patients who completed at least one treatment.


The investigators found that both formulations offered significant depression control. In fact, only one session (at any dose) provided “rapid” depression control among patients, the team noted.

Depression control also appeared to be effective over time, with some patients lasting up to a month after treatment. At the three-month mark, the team found that symptoms improved in 85% of patients and 40% were found to have depression. sorry.

Perhaps equally important, the team also found that “using lower concentrations of nitrous oxide also reduced the risk of side effects by four times.”

So, how does laughing gas ease depression?

“The mechanism of how nitrous oxide exerts an antidepressant effect is unknown, and how it induces sedation and relieves sedation and pain is different from this,” Nagel said. “Having said that, the most widely accepted theory is that nitrous oxide blocks a specific receptor in the brain called the NMDA-receptor, which is also thought to be the main mechanism for this. [the medication] Ketamine.”


Ketamine is a class III scheduled drug. While hospitals traditionally position the drug as an anesthetic, it has also been explored for its potential as an “off-label” treatment for depression.

According to Steven Holden, a professor of psychology at Vanderbilt University in Brentwood, Tenn., “ketamine is the hottest thing” in the world of alternative depression treatment research.

Holden was not involved in the new study, and admitted that he was not well-versed in the specifics of nitrous oxide depression treatment research. Still, he stressed that the finding “suggests a general mechanism” with ketamine. And he characterized Nagel’s work as “one of the most influential ‘proof-of-concept’ studies that makes me want to see this case move forward.”

The depression control seen in those patients exposed to low-dose laughing gas was “as good or better than you would expect to achieve in a placebo-controlled trial with antidepressant drugs, and these are treatment-resistant patients. [It’s] Quite impressive,” said Holden.

“If they come up with it as pilot data, I’ll fund them for a bigger test,” he said. “These are very promising findings.”


The report by Nagel and his colleagues was published in the June 9 issue of science translation medicine.

more information

There’s more on treatment-resistant depression Mayo Clinic.

SOURCES: Peter Nagel, Chair, Anesthesia and Critical Care, Department of Anesthesia and Critical Care, University of Chicago; Steven Holden, PhD, Professor, Psychology, Vanderbilt University, Brentwood, Tenn.; science translation medicine, June 9, 2021


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