Laughing gas works against severe depression

Nitrous oxide is a commonly-used anaesthetic - and seems to work against treatment-resistant depression...
15 June 2021

Interview with 

Peter Nagele, University of Chicago


A medical face mask for oxygen.


Laughing gas, at high concentrations, is a recreational drug that gives a sense of euphoria. But when mixed with oxygen, it’s one of the oldest drugs that we use in medicine - it’s an anaesthetic, and relieves pain. And now, doctors from the University of Chicago have found a new and surprising use for it in treating mental health. When they gave laughing gas - properly known as nitrous oxide, or nitrous - to people with severe depression, they found some extraordinary results. Anaesthesiologist Peter Nagele told Phil Sansom how they got their hunch...

Peter - Yes it does. And remarkably so. Not every patient does respond to nitrous oxide, but, in most patients it improves depressive symptoms really quickly, so within several hours. And a single inhalation may help patients up to two weeks or longer.

Phil - Wow. Is this just like one big breath in of nitrous oxide that you gave to a bunch of people? Or what is it?

Peter - No. So this is not like the recreational party drug use. It is much more like patients would get it in dentistry or in the emergency room. You know, you'd be in a chair or, you know, a hospital bed and inhaled this for about an hour through the face mask. And of course we always combine nitrous oxide with oxygen and it could be either 50-50 or what we've shown in the study, a lower concentration of 25% nitrous and the rest oxygen has similar efficacy.

Phil - Who were you giving this to? And out of those people, how many did it help?

Peter - These patients have been suffering from depression for close to 20 years and had run out of treatment options. And, you know, four out of five patients had an improvement in depressive symptoms, 'You know, I can see clearer now. The grey has gone out of my life. I'm more energized, I'm happier'. They may describe this within hours of the treatment.

Phil - That's remarkable, isn't it? I mean, these people had untreatable previously depression, 80% of them, you helped get better for weeks.

Peter - Yes. So for some patients, you know, the improvement in their depression lasted much longer. In some patients, you know, it started to come back after a week. It will be interesting to tailor the treatment to the individual patient to see, you know, how often would you need to repeat the treatment. But I agree with you. It is quite remarkable that the mass majority of patients really did see a treatment effect. Yes, I agree.

Phil - How can you be sure that it's not some sort of placebo effect happening?

Peter - Placebo effects are very common in studies or clinical trials in patients with mood disorders like depression, but it has become very apparent that the drug effect is much stronger than a simple placebo effect.

Phil - So is it just that people were blissed out by getting this drug or was something deeper happening?

Peter - When you look at most patients, the response to inhaling nitrous oxide is that basically they fall asleep. But asking what's going on in their brain is actually super important and super interesting. The way we think nitrous oxide works is similar to a drug called ketamine. And the discovery that ketamine has effects as an antidepressant has been considered one of the biggest breakthrough findings in depression research in the last 50 years. There's a receptive system in the human brain, that's called NMDA receptors, that must play a very important part. Now how this interacts is really, I think, one of the hottest areas right now in neuroscience, something must happen in the brain that it's like flipping a switch that will change how the brain operates. Right? And this may last, you know, as I said, for some patients for several weeks, and by that time, of course, nitrous oxide is long gone.


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