Laughing Gas vs Depression

Depression is no laughing matter, but one possible therapy just might be.

Before we get to that though, let’s be serious for a moment, and mention that if you found this in a search because you’re struggling with depression, then treatments of various kinds are well-worth pursuing, but here’s what will help you right now today this very moment:

• The Mental Health First-Aid That You’ll Hopefully Never Need ← no, we’re not going to ask you to name 5 things you can see and all that. That’s more to do with anxiety and disassociative disorders in any case. But what this article does have, is a lot of genuinely practical advice that actually works, and yes, even when your motivation is through the floor.
• How To Stay Alive (When You Really Don’t Want To) ← this one’s about as serious as it can get, and we mean it.

If, on the other hand, you’re in a much better mental state and just want to know how laughing gas works vs depression, then…

Can we just say N₂O to depression?

Researchers (Dr. Kiranpreet Gill et al.) examined data from hundreds of participants with major depressive disorder and/or treatment-resistant depression, taking single 25-50% nitrous oxide (N₂O) inhalation sessions, delivered for 20–60 minutes.

Here’s what Dr. Gill and her team found, in numbers:

❝Pooled results from three trials administering 50% N2O in a single session showed significant reductions in depressive symptoms at 2 h (pooled MD −2.74, 95% Confidence Interval (CI): −4.72 to −0.76; p = 0.007) and 24 h (MD −3.32, 95% CI: −5.09 to −1.55; p < 0.0001), but not at 1 week post-inhalation (MD −1.52; 95% CI: −4.07 to 1.03; p = 0.24). AEs were mild and transient, with 25% N2O generally being better tolerated. Evidence mapping showed that most trials are early-phase and focused on short-term outcomes in adults with MDD and TRD.❞

MD = Mean Difference
AE = Adverse Event
MDD = Major Depressive Disorder
TRD = Treatment-Resistant Depression

What they found, in few words: most patients experienced meaningful mood improvements within hours, some reaching remission by 24 hours. Which is a lot faster than most antidepressants! However, effects typically faded by one week later, albeit there were some outliers who enjoyed benefits for longer—including indefinitely, so far as observations have shown so far.

As one might expect, higher doses (50%) were more effective, while lower doses (25%) caused fewer adverse effects (e.g. nausea, dizziness, and headaches)

You might be wondering: would 100% be even more effective? And, technically yes, but only briefly, because then you would die of asphyxiation, because we need O₂ to live, and N₂O doesn’t have that, and 100% N₂O means 0% O₂.

As for how it works: you might think it has to do with making you laugh, but no! N₂O blocks NMDA receptors, modulates glutamate signalling, influences the default mode network, and affects dopamine and opioid pathways, offering a similar rapid-acting mechanism to ketamine, but with a much better safety profile.

You can read the paper in full, here: Nitrous oxide for the treatment of depression: a systematic review and meta-analysis ← including a diagram of a neuron showing how it works!

Want to learn more?

We’ve written quite a bit about ways to fight depression; here are a select few:

• Considering drugs? See: Antidepressants: Personalization Is Key!
• Not that kind of drugs? See: Here’s Why You Want To Know About Mushrooms and Depression
• Prefer nutraceuticals? See: 12 Foods That Fight Depression & Anxiety
• Want to get technological? See: Does This New Machine Cure Depression?
• Or just psychological? See: Behavioral Activation Against Depression & Anxiety

Take care!