Endocannabinoid (eCB) signaling has been linked to how the body and mind respond to endurance exercise, including what is often called the “runner’s high”. Even though humans can run for hours and in some cases days, knowledge of eCB signaling is largely limited to sessions shorter than 60 minutes. How these signals change over time during longer running therefore remains unclear.
Study Design: Endocannabinoid Levels Were Measured During Running
The study investigated eCB signaling during long-distance running and after a 45-minute break. In Study 1, 19 trained runners completed both a marathon and a duration-matched walking session, with repeated blood sampling every 14 km during the marathon and after 45 minutes of recovery. In Study 2, 36 ultramarathon runners completed races of 100, 160 or 230 km and provided blood samples before and after their respective races.
Plasma concentrations of anandamide (AEA), 2-arachidonoylglycerol (2-AG), 1-AG, arachidonic acid (AA) and palmitoylethanolamide (PEA) were quantified by a standardized liquid chromatography assay. Euphoria, anxiety and pain were assessed as core features of the “runner’s high” using visual analog scales.
Results: AEA Rises During Running — 2-AG Shows a Delayed Response
AEA increased progressively throughout the marathon and remained elevated even 45 minutes later, whereas walking only produced small changes. Similarly, after all ultramarathon distances, AEA levels were higher than before the race. By contrast, an increase in 2-AG during exercise was observed only in the regular marathon, where concentrations rose significantly during the later stages of running and into early recovery. Elevated post-race 2-AG levels were also seen after all ultramarathon distances, consistent with a delayed, recovery-related response.
Marathon running was associated with more euphoria and less anxiety than walking, while pain increased after 28 km. Ultramarathon running increased pain and reduced anxiety, but did not significantly change euphoria.
Conclusion: eCB Dynamics During Marathon and Ultramarathon in Two Field Studies
Together, the results show clear, time-dependent changes in circulating eCB concentrations during and after long-distance running, as well as gradual increases in AEA during walking. These eCB dynamics occurred alongside acute changes in mood and experience during endurance exercise.
Source:
Endocannabinoid dynamics across marathon and ultramarathon running: evidence from two field studies — BMC Medicine, 2026. DOI: 10.1186/s12916-026-05186-z
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