“Runner’s High” Depends on Endocannabinoids, Not Endorphins-
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In a double-blind, randomized, placebo-controlled experiment, the opioid-receptor antagonist naltrexone was used to assess whether euphoria and reduced anxiety levels, two core features of runners high, were dependent on opioid signaling. A cohort of 63 healthy adults (32 women, 31 men, 18-50 years of age) who regularly perform endurance exercise were included. Participants were randomized to receive either naloxone 50 mg or placebo before exercise; on two occasions separated by at least 30 days, participants performed moderate-intensity running or regular walking for 45 minutes on a treadmill. Standardized questionnaires and subjective grading were used to assess emotional state and the presence of runner’s high after exercise. Blood samples were collected and analyzed for endocannabinoids (eCBs).

Participants experienced increased euphoria and decreased anxiety after 45 minutes of running on a treadmill in a moderate-intensity range compared to walking. Running led to higher plasma levels of the eCBs anandamide and 2-arachidonoglycerol. Opioid blockade with naloxone did not prevent the development of euphoria and reduced anxiety or elevation of eCB levels following exercise. The fraction of participants reporting a subjective runner’s high was comparable in the naloxone (7 of 32) and the placebo-treated groups (5 of 31).

The authors concluded that this study indicates that the development of runner’s high in humans does not depend on opioid signaling; and makes eCBs strong candidates for agents responsible for runner’s high in humans, as previously demonstrated in mice.

Runner’s high describes a sense of well-being during endurance exercise, characterized by euphoria and anxiolysis. The release of endogenous opioids, such as endorphins, has been widely believed to be responsible for runner’s high. However, exercise is associated with the release of both opioids and eCBs, both classes of molecules potentially associated with reward processing.

This double-blind, randomized, placebo-controlled study revealed that running for 45 minutes compared to walking resulted in higher eCB levels, and that opioid-blockade with naloxone did not interfere with the development of subjective runner’s high. Although the scenario of a 45-minute treadmill run might not be the best scenario to induce runner’s high, the study provides provocative data suggesting that eCBs, not endogenous opioids, are responsible for runner’s high.

Source: https://www.sciencedirect.com/science/article/abs/pii/S0306453021000470
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