Endocannabinoid dynamics across marathon and ultramarathon running: evidence from two field studies.

Siebers M.; Huvermann D.; Siebers C.; Canales-Romero D.; Florea-Ghile A.; Keite L.; John L.; Munk M.; Bizjak R.; Witzel J. et al. · BMC medicine · 2026

**Background & Methods** Two field studies examined endocannabinoid (eCB) signaling dynamics during prolonged endurance exercise. Study 1 involved 19 trained runners completing a marathon with repeated blood sampling every 14 km and after 45-minute recovery, compared to a duration-matched walking session. Study 2 enrolled 36 ultramarathon runners completing races of 100 km, 160 km, or 230 km with pre- and post-race blood sampling. Plasma concentrations of anandamide (AEA), 2-arachidonoylglycerol (2-AG), 1-AG, arachidonic acid (AA), and palmitoylethanolamide (PEA) were quantified using liquid chromatography/multiple reaction monitoring assay. Affective responses (euphoria, anxiety, pain) were assessed via visual analog scales. **Key Findings** • AEA increased progressively throughout marathon running and remained elevated after 45-minute recovery, with only modest changes during walking. Similarly, elevated AEA levels were observed after all ultramarathon distances compared to baseline, indicating a robust, sustained eCB response to prolonged endurance exercise. • 2-AG concentrations increased significantly during later marathon stages and into early recovery; post-race 2-AG elevation was also observed following all ultramarathon distances, suggesting a delayed, recovery-related eCB response pattern distinct from AEA dynamics. • Marathon running demonstrated higher post-exercise euphoria and lower anxiety compared to walking, though pain increased after 28 km. Ultramarathon running increased pain and reduced anxiety but did not significantly alter euphoria, indicating distance-dependent differences in affective responses accompanying eCB signaling changes. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Not reported. **Evidence Quality** This review synthesizes field-based observational data from relatively modest sample sizes (N=19 and N=36), limiting generalizability. The absence of a control group in Study 2 and lack of randomization reduce causal inference strength. Confounding variables (training status, pacing strategies, nutritional intake, environmental factors) were not controlled. The reliance on peripheral blood sampling may not reflect central nervous system eCB dynamics. Affective measures using visual analog scales are subjective. However, the longitudinal design with repeated sampling and standardized bioanalytical methodology represent methodological strengths. Overall evidence quality is moderate, appropriate for exploratory field investigations but insufficient for definitive mechanistic conclusions regarding eCB-mediated runner's high phenomena.

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