You might have used laughing  gas, AKA nitrous oxide, at the dentist’s office.

After  all, it’s the most common gaseous anesthetic in the world. Even the name sounds appealing.  If you’re walking into a situation that you know is about  to be painful, just laugh it off!

But laughing gas does more than just take away your pain at the dentist. Recent studies suggest it may treat the least funny thing imaginable: depression. [♪ INTRO] There’s an old saying that  “laughter is the best medicine.” And one study published in 2012 put the adage to the test with a simple  measure of pain tolerance. They used frozen sleeves and blood pressure cuffs on participants o create  cold and restricted feelings, and measured how well they  tolerated that un-fun feeling.

The researchers split the people into two groups: one that watched a video on something serious and another that watched something funny. As you might expect, the comedy group laughed more than the serious group. And when the researchers tested  everyone’s pain tolerance after watching the videos, they found  that the group that watched clips from Mr.

Bean or the Simpsons  had higher pain thresholds and lasted significantly longer  in those uncomfortable conditions than people who watched a lecture or the news. To paraphrase the great Elle Woods, laughter gives you endorphins.  And endorphins make you happy! More specifically, endorphins bind  to opioid receptors that block pain.

And even though it doesn’t  actually force you to laugh, laughing gas is a great option  for managing pain at the dentist. One huge benefit is that it works really fast. Nitrous oxide moves through  your bloodstream without binding to hemoglobin or  turning into anything else.

So you can feel its effects quickly. When it gets to its destination, it hops off the Bloodstream Express and  travels to specific sites on your brain cells called NMDA  receptors and blocks them. This is similar to the way  ketamine works, which makes sense because both nitrous oxide and  ketamine are used as anesthetics.

But the thing is, those NMDA  receptors that nitrous binds to control a lot of your brain’s  activity, not just pain signaling. For example, some depression treatments also involve your NMDA receptors. Which is getting today’s  researchers excited about a new therapeutic future for  laughing gas on top of your teeth.

Well really above them, and  then kind of behind them. …It’s your brain, I’m talking about your brain. And it looks like nitrous  oxide makes a big difference in the brains of people with  treatment-resistant depression. See, antidepressants don’t work for about 20% of people with clinical depression.

But a 2023 publication  suggests that nitrous oxide can quickly do the job that other  antidepressant treatments can’t. In that study, participants  diagnosed with treatment-resistant depression were all given face masks with either a nitrous oxide-oxygen mixture or an oxygen placebo. People who received nitrous oxide  scored significantly lower on a depression assessment than  the people in the placebo group.

So nitrous oxide could someday be  an effective treatment for people who’ve had trouble finding an  effective antidepressant in the past! While researchers are still  unpacking exactly why this one gas can do two different  things, they have some ideas. See, the nitrous oxide group had  more active functional connectivity networks than the placebo group, which basically   means that more parts of the brain  were communicating with each other.

More specifically, it seems like the attention circuits in the brain were affected. So it’s possible that  nitrous oxide is manipulating your brain’s attention circuits  by increasing the activity and connection between  different parts of the brain. Like, when you use laughing  gas, the attention-regulating frontal lobe might become more  linked to other parts of the brain.

And we know from previous studies  that attention is controlled differently in people with depression  diagnoses than in people without. So this nitrous oxide treatment might help remove the negative attention  bias that some people with treatment-resistant depression have. Basically, it helps you  stop focusing on bad stuff.

And so far, things are looking good. Researchers are still testing  if nitrous oxide can be used long-term against  treatment-resistant depression, but the early reports are promising. For anyone who might be considering using nitrous oxide recreationally, though, a warning: In its unregulated form, the gas can  leave you with long term problems.

When you have too much of it in your system, it can oxidize and inactivate vitamin B12, which can cause some gnarly  neurological side effects. That’s why dentists are careful not to overload your system with too much all at once. The professionals at your  dentist’s office give you nitrous oxide in low doses mixed  with a lot of oxygen to make sure you don’t have too much  in your body at any one time.

As usual, it’s best to take  mind-altering substances under the supervision and recommendation of  a trained medical professional. Once they finish conducting  long term safety tests, we might be saying that laughing  gas is the best medicine. [♪ OUTRO]