Endocannabinoids or Endorphins? The Truth Behind The “Runner’s High”

Illustrated by Shanthi Deivanayagam

Your feet pound on the pavement, sweat beads on your forehead and your muscles ache as you hit the 10 mile mark on your morning run. However, you don’t just experience the sense of accomplishment you normally do; instead, you experience a sensation of pure bliss, your anxiety, stress and pain easing as you continue on down the street.  

A “runner’s high” is a feeling of euphoria experienced occasionally by long-distance runners and is often accompanied by decreased levels of anxiety and pain. While this high has been thought to be the result of increased B-endorphins (neuropeptides that are involved in pain management and which have morphine like effects), it has been recently discovered that the high is actually due to the release of endocannabinoids in the body [7]. Two main contributors to the runner’s high sensation are anxiolysis (a level of sedation in which one is relaxed but awake) and analgesia (the inability to feel pain without loss of consciousness) [3,5].

In the peripheral nervous system (the part of the nervous system outside of the brain and spinal cord), the B-endorphins produce analgesia by binding to opioid receptors, so they are part of the body’s opioid system. In the body’s endocannabinoid system, on the other hand, the cannabinoid receptor 1 (CB1) receptors work at the peripheral terminals of primary sensory neurons to induce analgesia, and at the forebrain GABAergic neurons, CB1 receptors cause anxiolysis [4]. The endocannabinoid system operates throughout the central nervous system, rather than the peripheral nervous system like endorphins do. This allows for the distinction between endorphins being the root cause of the runner’s high versus endocannabinoids, as endorphins do not reach the brain, instead staying in the peripheral nervous system. 

Researchers Johannes Fuss, et al. from the Heidelberg University Faculty of Medicine in Mannheim, Germany, believe that the endocannabinoid system is a more likely candidate for the root of the runner’s high because endorphins cannot pass through the selectively permeable blood-brain barrier to trigger a high in the brain. Both B-endorphins and the endocannabinoid anandamide have been found to be at increased concentrations in the blood after running, and since anandamide is lipid-soluble, it can traverse the blood-brain barrier. Thus, this endocannabinoid in particular was what Fuss and his team researched in mice [2].

In Fuss’ 2015 paper titled “A runner’s high depends on cannabinoid receptors in mice,” the researchers studied mice and used running wheels to model humans performing long-distance running as exercise. The mice were tested for anxiety by using a dark-light box test, which shows when mice have less anxiety as they move into the aversive bright area for longer periods of time. The experimental group were those mice that ran on wheels for five hours, while the control group did not run. Comparing the experimental running group with the control mice, those that ran displayed less anxiety [1].

To test pain sensitivity, mice underwent a hot plate test, in which mice were exposed to a hot plate and those who jumped back or licked their paws showed a pain response. The researchers found after their experiments that the mice who ran had a decreased pain response because they took significantly longer to either jump or lick their paws [1]. These two tests supported the hypothesis that long-distance running induces a high which is characterized by reduced anxiety (anxiolysis) and decreased pain sensitivity (analgesia). After collecting and testing the mice plasma and other body tissues, the researchers found that there were significantly higher levels of endocannabinoids in the plasma of the mice who ran versus the controls [1].

Then, the experiment was conducted again, this time with two groups of mice: one with an endocannabinoid antagonist (a molecule that blocks cannabinoid receptors) and another with an endorphin antagonist (a molecule that blocks endorphin receptors). The endorphin antagonists had no effect on anxiolysis or analgesia, while the endocannabinoid antagonist-treated mice experienced both anxiety and pain even after running for the same amount of time [2].

In a more recent study published in February of 2021 by Fuss along with researchers Michael Siebers, Sarah V. Biedermann, Laura Bindila and Beat Lutz, 63 human participants were studied and they found that anxiety decreased and euphoria increased after 45 minutes of running on the treadmill compared to walking [6]. After studying the participants’ plasma, higher levels of the endocannabinoid anandamide and 2-arachidonoylglycerol were found in the runners. Additionally, like the mouse study, blocking opioids through endorphin antagonists did not change the high that the runners experienced or the levels of endocannabinoids in their plasma [6].

Because of these new findings, the true cause for the euphoric runner’s high sensation can now be more accurately attributed to endocannabinoids and the body’s endocannabinoid receptor system, rather than endorphins. So, the next time you go on a run and feel the euphoric runner’s high, you can thank your endocannabinoids instead of the famous endorphins everyone always seems to give all the credit to. 

Edited by: Neha Adari
Illustrated by: Shanthi Deivanayagam

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