What gets you high when you run isn’t morphine. It’s closer to cannabis.

Endorphins are naturally occurring brain chemicals; the name is a portmanteaux of endo genous (meaning “within”) and morphine. This week a collaborative study centered at the University of Heidelberg in Mannheim, Germany published a paper in the Proceedings of the National Academy of Sciences (PNAS) exploring how a different set of chemicals, the endocannabinoids (a similar portmanteaux of cannabis), are responsible for the production of a runner’s high.

Endorphins are indeed produced when exercising, but they’re manufactured in strangely. One brain region produces endorphins for the brain, and another produces them for the body. Endorphins actually can’t pass through the blood-brain barrier, so these quantities are somewhat independent. Endocannabinoids, on the other hand, can pass directly from blood to brain. Understanding this, lead author Dr. Johannes Fuss and his colleagues hypothesized that endocannabinoids were a much better candidate for explaining what makes runners and cyclists feel good when they exert themselves.

To test this, Fuss examined mice. “If you place a running wheel in a mouse’s cage, it will run voluntarily, covering great distances of about 10 km/day over twelve hours each day,” he says. “They’re really motivated to run; there are strong biological processes motivating these mice to run in running wheels, therefore they’re a good model to study why humans are motivated to do exercise.”

To get a baseline effect of exercise on mouse physiology, Fuss and his colleagues habituated a population of mice to running on wheels, and separated them into two groups. One group was allowed to run before a series of behavioral experiments, and the other was not. Their anxiety and pain sensitivity were measured, demonstrating that when mice were allowed to run they experienced less of each. Expectedly, endocannabinoids were shown to increase in the running mice.

To show that it was the endocannabinoids rather than the endorphins causing these runner’s-high effects, Fuss and his colleagues did something creative. The mice were introduced to drugs that block the receptors of either the endorphins or the endocannabinoids. According to Fuss, “What we found was blocking the endorphin receptors didn’t change anything physically. The mice were still running and still less anxious, and they still experienced less pain. In contrast, when blocking endocannabinoid receptors, the mice were no longer less anxious or had reduced pain sensitivity.”

In a last experiment, a group of mice were genetically altered, what Fuss explained as “in the forebrain they had no cannabinoid receptors.” These mice don’t experience a runner’s high anymore. If you put a wheel in these mice’s cages, “initially they run comparable distances,” he says, “but after a couple of days they don’t run very much anymore. Probably because they don’t have this emotional benefit from running; it’s kind of boring for them.”

For future experiments, there may be more mouse experiments investigating which brain structures are involved. According to Fuss, it would be interesting “seeing how they’re activated or inhibited by the endocannabinoids.” There’s also a tremendous amount of research to be done in humans, specifically why some people experience a runner’s high and others do not. Says Fuss, “We could measure endocannabinoids in the blood and see whether there are differences between different humans, different excise schedules, and so on.”