What causes runner's high?

The answer

Runner's high, the feeling of euphoria, reduced anxiety, and diminished pain during sustained exercise, was long attributed solely to endorphins. However, research has revealed that endorphins are too large to cross the blood-brain barrier efficiently. The primary mediator is now thought to be endocannabinoids, particularly anandamide, lipid-soluble molecules produced during aerobic exercise that easily enter the brain and activate the same cannabinoid receptors targeted by THC in cannabis. Studies in mice showed that blocking endocannabinoid receptors eliminated runner's high behaviors while blocking opioid receptors did not. In humans, endocannabinoid levels increase significantly after about 30 minutes of moderate-to-intense exercise. The combined action of endocannabinoids (for euphoria and anxiety reduction) and endorphins (for pain relief) creates the full runner's high experience.