The endocannabinoid system plays a crucial role in maintaining balance within the body, influencing various aspects such as emotion, pain perception, metabolism, prenatal development, and the gut microbiome. THC, a cannabinoid found in cannabis, affects the brain’s cannabinoid receptors, particularly CB1 receptors, which are present not only in the brain but also in organs like the lungs and cardiovascular system. This suggests a potential relationship between cannabinoids and physical activity, impacting exercise performance.

Research indicates that physical activity affects the endocannabinoid system, with an increase in anandamide levels observed following exercise. Anandamide and 2-AG are the two major endogenous cannabinoids. Studies, both clinical and preclinical, conducted since the 2010s have shown that acute exercise leads to a rise in anandamide levels, irrespective of the type of exercise or the subjects’ health conditions. However, the effects of exercise on 2-AG levels are less consistent, and the impact of chronic exercise remains unclear.

Animal studies reveal that both voluntary exercise and palatable food consumption have similar effects on the endocannabinoid system. CB1 receptors in the brain, crucial for reward processing, influence the rewarding effects of various activities, including exercise. Wheel running and sugar consumption in mice, for example, increase the sensitivity of CB1 receptors to cannabinoids. This suggests that an animal’s physical activity and dietary patterns can modify its response to cannabinoids.

Mice exhibit an acute elevation in blood endocannabinoid levels following running wheel exercise, similar to the “runner’s high” experienced by long-distance human runners. This phenomenon involves a feeling of euphoria, reduced anxiety, and pain relief. Such effects depend on CB1 receptors in specific brain neurons, highlighting the endocannabinoid system’s role in coordinating changes in response to physical activity across the brain and body.

The evolutionary perspective sheds light on why animals, including humans, are wired to respond to physical activity by altering their endocannabinoid system. Higher endocannabinoid levels following exercise may signal a depletion of energy stores, motivating animals to seek food and explore their environment. Throughout human evolution, physical exertion was essential for acquiring calories, explaining why biological mechanisms prepare the body for energy utilization and storage after exercise.

Modern health issues such as metabolic dysfunction and anxiety may stem from mismatches between our evolved biology and contemporary lifestyles. With easy access to abundant calories, our bodies, primed for storing fat reserves, remain in a perpetual rest-and-digest mode. Moreover, the absence of life-threatening food scarcity allows new anxieties to arise. Intentional use of exogenous cannabinoids like THC further alters the endocannabinoid system, raising questions about their impact on exercise performance