Endocannabinoid signaling shows robust, time-dependent changes during prolonged endurance running, with AEA increasing progressively throughout marathon running and remaining elevated after 45 minutes, while 2-AG increases appear delayed and recovery-related, occurring alongside acute affective changes including euphoria, reduced anxiety, and increased pain.
Key Findings
Results
AEA (anandamide) increased progressively throughout marathon running and remained elevated after a 45-minute recovery period.
Study 1 included 19 trained runners who completed both a marathon and a duration-matched walking session with repeated blood sampling every 14 km.
AEA increases were progressive across the marathon distance, not simply an acute response at race start.
AEA remained elevated even after a 45-minute break following the marathon.
Walking elicited only modest changes in AEA, contrasting with the more pronounced marathon-induced response.
Plasma concentrations were quantified by a standardized liquid chromatography/multiple reaction monitoring assay.
Results
AEA levels were increased compared with baseline after all ultramarathon distances (100 km, 160 km, and 230 km).
Study 2 included 36 ultramarathon runners completing races of 100 km, 160 km, or 230 km.
Blood samples were provided before and after the respective races.
The finding was consistent across all three ultramarathon distances, suggesting a robust exercise-induced AEA response regardless of extreme distance.
This extends evidence of AEA elevation beyond the previously studied sub-60-minute exercise bouts.
Results
2-AG (2-arachidonoylglycerol) increases during exercise were observed only in the regular marathon, rising significantly during the later stages of running and into early recovery.
In Study 1, 2-AG concentrations rose significantly during the later stages of marathon running.
2-AG increases extended into early recovery, suggesting a delayed rather than immediate exercise response.
By contrast, 2-AG did not show a significant increase during exercise in the same pattern observed in the ultramarathon context.
Elevated post-race 2-AG levels were also observed following all ultramarathon distances in Study 2, consistent with a 'delayed, recovery-related response.'
Results
Marathon running was associated with higher euphoria and lower anxiety compared with walking.
Euphoria, anxiety, and pain were assessed as core features of the runner's high using visual analog scales.
The comparison was within-subjects, as the same 19 runners completed both marathon and duration-matched walking sessions.
Pain increased after 28 km of running during the marathon.
Walking elicited only modest affective changes compared to marathon running.
Results
Ultramarathon running increased pain and reduced anxiety post-exercise but did not significantly alter euphoria.
36 ultramarathon runners completed races of 100 km, 160 km, or 230 km.
Pain was elevated post-race across ultramarathon distances.
Anxiety was reduced following ultramarathon races.
Euphoria was not significantly changed after ultramarathon running, contrasting with the significant euphoria increase seen in marathon runners compared to walkers.
Affective outcomes were assessed using visual analog scales before and after the races.
Results
Walking elicited only modest eCB changes, including gradual increases in AEA, suggesting that exercise intensity and/or modality influences endocannabinoid dynamics.
The walking session was duration-matched to the marathon, allowing direct comparison.
AEA showed gradual increases even during walking, though these were more modest than marathon-induced changes.
The contrast between walking and running conditions highlights that eCB responses are not purely duration-dependent.
This finding extends prior literature that was largely limited to bouts shorter than 60 minutes.
Background
Prior evidence on endocannabinoid signaling during exercise was largely limited to bouts shorter than 60 minutes, leaving eCB temporal dynamics during prolonged running unclear before this study.
The authors note that 'although humans have the capacity to run for several hours and even days, evidence regarding eCB signaling is largely limited to exercise bouts shorter than 60 min.'
This study addresses the gap by sampling every 14 km during a full marathon and measuring post-race in ultramarathons up to 230 km.
The repeated blood sampling design in Study 1 allowed characterization of temporal dynamics rather than just pre-post comparisons.
Methods
Plasma concentrations of AEA, 2-AG, 1-AG, arachidonic acid, and palmitoylethanolamide (PEA) were measured using a standardized liquid chromatography/multiple reaction monitoring assay across both field studies.
Five lipid mediators were quantified: anandamide (AEA), 2-arachidonoylglycerol (2-AG), 1-AG, arachidonic acid (AA), and palmitoylethanolamide (PEA).
The same standardized LC/MRM assay was used across both studies, enabling methodological consistency.
Study 1 used repeated blood sampling every 14 km and after 45-minute recovery; Study 2 used pre- and post-race sampling.
Both studies were conducted as field studies rather than laboratory settings, reflecting real-world endurance events.
What This Means
This research suggests that long-distance running causes meaningful changes in the body's endocannabinoid system — a network of chemical signals that influence mood, pain, and wellbeing — and that these changes build up progressively over the course of a run rather than occurring all at once. The study tracked two key endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in runners during a full marathon and in ultramarathon runners completing races of 62, 100, or 143 miles. AEA climbed steadily throughout the marathon and stayed elevated even 45 minutes after finishing, and was also elevated after all ultramarathon distances. 2-AG appeared to rise more in the later stages of running and during recovery, suggesting it follows a different, more delayed pattern.
The mood effects of these runs were also notable. Marathon runners reported higher feelings of euphoria and lower anxiety compared to walking for the same amount of time, though pain increased after about 17 miles of running. Ultramarathon runners experienced increased pain and reduced anxiety after their races, but did not report a significant boost in euphoria — possibly because the extreme physical demands overshadow pleasurable feelings, or because euphoria may have occurred during the race but subsided by the time post-race measurements were taken.
This research matters because most previous studies on endocannabinoids and exercise only looked at short bouts of activity — typically less than an hour — and the 'runner's high' phenomenon has been difficult to study systematically. These findings show that endocannabinoid signaling continues to shift across many hours of running, which helps explain why some runners describe mood and pain experiences that change as a race progresses. The results could inform future research into how sustained physical activity affects brain chemistry and emotional wellbeing.
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Siebers M, Huvermann D, Siebers C, Canales-Romero D, Florea-Ghile A, Keite L, et al.. (2026). Endocannabinoid dynamics across marathon and ultramarathon running: evidence from two field studies.. BMC medicine. https://doi.org/10.1186/s12916-026-05186-z