Endurance exercise can induce a transient euphoric state known as the runner's high, characterized by euphoria, anxiolysis, hypoalgesia, and a subjective sense of flow. Traditionally, this phenomenon has been interpreted within an "either-or" framework, attributing its emergence primarily to β-endorphins or, more recently, to the endocannabinoid (eCB) system. The aim of this narrative review is to move beyond this dichotomy and to present an integrative neuromodulatory perspective on the runner's high, with a focus on the eCB system as a central coordinating mechanism. We integrate evidence from human and animal studies showing that circulating eCBs reliably increase during moderate-intensity endurance exercise and are consistently associated with core affective features of the runner's high. At the same time, we consider the complementary roles of other neuromodulators: β-endorphins primarily regulate pain and stress responses; brain-derived neurotrophic factor supports neuroplasticity; serotonin and dopamine modulate mood and motivation; noradrenaline and adrenaline facilitate arousal; and leptin links the metabolic state to movement and motivation. Overall, the runner's high appears to reflect an orchestrated neuromodulatory response in which the eCB system occupies a prominent integrative role.
Keywords: adrenaline; brain-derived neurotrophic factor (BDNF); dopamine; endocannabinoids; endurance exercise; leptin; neuromodulation; noradrenaline; runner’s high; serotonin; β-endorphins.