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Exploring The Molecular Basis Of “Runner’s High”

Neuroscience: Exercise-induced endocannabinoids decrease anxiety and pain perception in mice, study suggests

by Judy Lavelle
October 5, 2015

Credit: Shutterstock
Mice can display symptoms of “runner’s high”—less anxiety and a diminished ability to feel pain—study suggests.
Credit: Shutterstock
Mice can display symptoms of “runner’s high”—less anxiety and a diminished ability to feel pain—study suggests.

After a nice long bout of aerobic exercise, some people experience what’s known as a “runner’s high”: a feeling of euphoria coupled with reduced anxiety and a lessened ability to feel pain. For decades, scientists have associated this phenomenon with an increased level in the blood of β-endorphins, opioid peptides thought to elevate mood.

Now, German researchers have shown the brain’s endocannabinoid system—the same one affected by marijuana’s Δ9-tetrahydrocannabinol (THC)—may also play a role in producing runner’s high, at least in mice (Proc. Natl. Acad. Sci. USA 2015, DOI: 10.1072/pnas.1514996112).

The researchers hit upon the endocannabinoid system as possibly being involved because they observed that endorphins can’t pass through the blood-brain barrier, says team member Johannes Fuss, who’s now at University Medical Center Hamburg-Eppendorf. On the other hand, a lipid-soluble endocannabinoid called anandamide—also found at high levels in people’s blood after running—can travel from the blood into the brain, where it can trigger a high. “Yet no one had investigated the effects of endocannabinoids on behavior after running,” Fuss says.

To explore how endocannabinoids are involved, the team familiarized a group of mice with running on an exercise wheel regularly. Then the researchers split the group into two sets of mice: one that would run for five hours and one that would remain sedentary. Soon after their five-hour run, the rodents in the first group displayed far less anxious behavior than the sedentary set when exposed to a so-called dark-light box test. In this test, a mouse’s anxiety is measured by the frequency with which the animal darts from well-lit areas into the dark to hide.

Similarly, mice in the running group had a higher tolerance for pain than those in the sedentary group, as measured by their tendency to jump or lick their paws when placed on a hot plate.

Finally, the researchers performed these same experiments on mice that were given endocannabinoid and endorphin antagonists—molecules that block cannabinoid and opioid receptors in the brain, respectively. The endorphin antagonists did not significantly affect results, but mice treated with endocannabinoid antagonists and mice genetically engineered to lack endocannabinoid receptors were still anxious and sensitive to pain despite having run for hours.

The team’s findings suggest that endocannabinoids such as anandamide help cause runner’s high. “The authors have moved the field forward by providing such a complete view of how this key reward system is involved in allowing exercise to improve psychological state and pain sensitivity,” says David A. Raichlen, an expert in human brain evolution and exercise at the University of Arizona.

The researchers write that other key aspects of runner’s high, such as euphoria, are too subjective to study in a mouse model.



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Anonymous (October 7, 2015 8:36 AM)
No wonder I love running so much....seriously !
Larry Duncan (October 8, 2015 9:58 AM)
An appropriately named molecule since Ananda means bliss. I enjoyed this well written and understandable summary.
Dan Wixom (October 10, 2015 3:09 PM)
They test for pain by putting mice on a hot plate? Heartless assholes, especially when you figure their experiment proved nothing. Maybe we can arrange to have these scientist tested for pain.
Anonymous (October 26, 2015 5:48 PM)
This study showed a correlation in enzyme activity to a certain stimuli. Also the temperatures were mildly discomfortable at most because if it had been higher the running mice would also have been in pain, running doesn't/didn't make them impervious to pain.
Bailey (April 18, 2017 8:59 AM)
Hey! Loved the article, hate running though lol
Mark Lilly (June 22, 2017 10:18 AM)
Just like "runner's high", I get the same feeling after a long period on the bicycle. After many miles of cycling at a brisk pace, I get the same euphoria that is described in the article. I used to be a marathon runner and the feeling is the same after each type of exercise. It seems as though, the longer the workout, the greater the feeling of euphoria and the longer it will last. It lasts for many days after running a marathon and riding a bicycle century (100 miles). This takes much longer than running a marathon, more in the neighborhood of five to six hours on the bike. I believe that this feeling of euphoria can occur during every daily workout also because every time that you complete a workout, you feel as though you have completed a great accomplishment.

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