There's possibly no better feeling than the calm and happiness that follow the completion of a long, tough run.

So where does this so-called 'runner's high' come from?

You've probably heard it get chalked up to a rise in endorphins, the 'happy' chemicals that induce feelings of pain relief and pleasure. But it's actually more complicated than that.

The 'endorphins make you happy' idea

The idea that increased levels of endorphins are responsible for that post-workout happy feeling came out of 1980s research that showed endorphin levels in the blood spiked after prolonged exercise.

Some researchers assumed these chemicals must also produce the sense of euphoria we feel after a workout.

But recent studies in mice suggest that endorphins actually might not have anything to do with the runner's high.

The problem with the endorphin explanation is that they're very large molecules - so large, in fact, that they can't move from the blood into the brain.

The blood-brain barrier is key to keeping the brain safe, since it stops certain pathogens and molecules from passing from the blood into the brain.

Because endorphins can't get through, it's unlikely that they are the sole chemical responsible for the feelings associated with vigorous exercise.

Instead, scientists think the effect can be attributed to other chemicals in the body that produce similar pain-relieving and happy feelings.

Turning to endocannabinoids

Levels of a chemical called anandamide also increase when you exercise, according to a 2015 study in mice and a small 2004 study in people.

Anandamide is a type of endocannabinoid, a chemical that's part of the system that moderates the psychoactive, feel-good effects of marijuana. And unlike cumbersome endorphins, anandamide can smoothly make its way from the blood to the brain.

For the 2015 paper, researchers at the Central Institute of Mental Health at the University of Heidelberg medical school compared the effects of endorphins and endocannabinoids on mice as they ran on running wheels.

The researchers found that, in addition to appearing calmer and less sensitive to pain after running, the mice had higher levels of both endorphins and endocannabinoids.

The animals also spent more time in well-lit parts of their cage, something calm, less anxious mice tend to do. They were also slightly more pain-tolerant after their stints on the wheel.

To measure the effects of each chemical individually, the researchers gave the mice drugs that blocked the effects of each. When they blocked the endorphins, nothing happened - the animals remained more relaxed and pain-tolerant.

But when they blocked the effects of the endocannabinoids, the symptoms of the mice's runner's highs disappeared.

These findings suggest that the mice's elevated endorphin levels had little to do with their post-workout buzz.

This research has one obvious caveat, however: Mice aren't humans. And the study also revealed, disappointingly, that you probably need to run pretty far to experience a runner's high. The mice ran an average of more than three human miles per day (a long way for a mouse).

If you're interested in learning more about the connection between endocannabinoids and runners' highs, this video from YouTube channel SciShow walks through some of the evidence.

Other factors at play

Other studies, however, suggest that neither endorphins nor endocannibinoids are the cause of the runner's high. A 2015 study, for example, found that mice with low levels of a hormone called leptin tended to run farther than mice with normal levels of leptin.

Leptin, otherwise known as the "satiety hormone," inhibits the feeling of hunger in order to regulate our energy levels.

The idea is that the less full (or more hungry) you feel, the more motivated you are to keep running. And that increased motivation might make it easier to get a runner's high.

"Ultimately, leptin is sending the brain a clear message: When food is scarce, it's fun to run to chase some down," lead study author Maria Fernanda Fernandes told Outside Magazine in 2015.

But again, the fact that these results have been demonstrated in mice doesn't mean the same effects will necessarily be found in humans.

And because there might be a combination of factors at play, definitive evidence of what exactly causes a runner's high might continue to elude scientists for a while.

This article was originally published by Business Insider.

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