If you’re someone who enjoys distance running, you might’ve felt a sensation of happiness, calm, or reduced pain that sets in after a workout—commonly known as runner’s high.

Since the 1980s, runner’s high was thought to be caused by chemicals called endorphins. Remember the line from Legally Blonde? “Exercise gives you endorphins, and endorphins make you happy!” But now, scientists aren’t convinced that endorphins should get all the credit.

The real culprit might be endocannabinoids, a group of chemicals in your body that act like the compounds in marijuana that cause a high. Endorphins bind to what are known as opioid receptors on neurons all over your body, affecting other chemical signaling that your brain interprets as pain. Because endorphins can cause pain relief in your muscles, they were thought to cause all the feel-good parts of runner’s high.

But endorphins, it turns out, are too big to pass through the blood-brain barrier, a highly selective membrane that protects the brain from potentially harmful stuff in the bloodstream. So they probably don’t cause the general feelings of happiness that come with runner’s high, because they’re not interacting with brain cells. Instead, scientists think it might be the endocannabinoids.

Endocannabinoids interact with the same systems in your brain as THC in marijuana does, but your body naturally makes them. They’re involved in things like soothing anxiety and reducing pain sensitivity. In 2015, a group of researchers showed that mice produced more of an endocannabinoid called anandamide after running on a wheel for around 6 kilometers.

To test for the pain-relief that comes with runner’s high, mice who ran and mice who didn’t were placed on a hot plate to cause pain. And the mice who ran had more anandamide in their blood and took longer to get noticeably agitated on the hot plate. Then, the researchers ran the experiment again.

This time, they gave some of the running mice a drug to block endorphins from having any effect, but the mice still acted calmer when they were plopped on a hot plate. The researchers gave other running mice a drug that blocks anandamide from binding to receptors. These mice were more anxious and sensitive to the hot plate—just like the non-runners.

So, according to this study, it seems like anandamide contributes to the pain and anxiety relief of runner’s high, but endorphins not so much. At least in mice. But what about humans?

In 2012, a study had a few humans, dogs, and ferrets run on treadmills for half an hour, and found that endocannabinoid levels in blood went up in humans and dogs—which are both better adapted to running. And a 2011 study involving 11 healthy male cyclists suggested that anandamide production from exercise might increase neurotrophin levels, a kind of protein that can adjust connections between neurons, and have some antidepressant effects.

Because of small sample sizes, though, it’s hard to say if these studies mean something for all of us. So there’s a good chance that endocannabinoids could be involved in runner’s high, but there’s a lot we still don’t understand about our bodies!

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