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The runner’s high is an ephemeral feeling some humans experience during and after endurance exercise. Recent evidence in mice suggests that a runner’s high depends on the release of endocannabinoids (eCBs) during exercise. However, little is known under what circumstances eCBs are released during exercise in humans. This systematic review sampled all data from clinical trials in humans on eCB levels following exercise from the discovery of eCBs until April 20, 2021. PubMed/NCBI, Ovid MEDLINE, and Cochrane library were searched systematically and reviewed following the PRISMA guidelines. From 278 records, 21 met the inclusion criteria. After acute exercise, 14 of 17 studies detected an increase in eCBs. In contrast, after a period of long-term endurance exercise, four articles described a decrease in eCBs. Even though several studies demonstrated an association between eCB levels and features of the runner’s high, reliable proof of the involvement of eCBs in the runner’s high in humans has not yet been achieved due to methodological hurdles. In this review, we suggest how to advance the study of the influence of eCBs on the beneficial effects of exercise and provide recommendations on how endocannabinoid release is most likely to occur under laboratory conditions.

Do Endocannabinoids Cause the Runner’s High? Evidence and Open Questions