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Widely distributed throughout the body and central nervous system, the endocannabinoid system (ECS) is a significant modulator of health. This intricate, cellular signaling network is pivotal for governing homeostasis across the body’s systems. A growing body of research underscores the role the ECS has in maintaining health, with emerging findings demonstrating the impact exercise has in supporting this regulatory system.
The ECS comprises endogenous cannabinoids, or endocannabinoids (eCBs)—lipid-based neurotransmitters produced in the body that can cross the blood-brain-barrier—and enzymes that regulate their synthesis or degradation. This complex system functions through endogenous and exogenous forms of cannabinoids (cannabidiol CBD, tetrahydrocannabinol THC) interacting or binding to these receptors to exert its homeostatic functions.
Dispersed heavily in the central and peripheral nervous system, CB1 receptors influence mood, stress, pain perception, and sleep. Predominantly expressed in peripheral tissues, including the intestinal epithelium and immune cells, activation of CB2 receptors promotes modulation of inflammation, gut motility, intestinal homeostasis, and the immune response.
The most studied endocannabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). AEA has been shown to have roles in regulating inflammation, anxiety and energy metabolism, while 2-AG has been implicated to have modulating functions in neurotransmitter release, emotional regulation, pain perception, energy and neuroinflammation.
Mounting research demonstrates that exercise increases circulation of these endogenous cannabinoids (eCBs), having vast homeostatic effects, notably relative to stress and metabolism. A 2022 systematic review and meta-analysis revealed that exercise increased eCB signaling, producing the mood enhancing and analgesic properties associated with exercise. Systematic review of thirty-three studies, reporting on fifty-seven samples, demonstrated that exercise induced significant increases in AEA mobilization, with inconsistent findings in 2-AG. Meta-analysis of ten studies showed increases in circulating levels of both AEA and 2-AG from exercise.
These observed effects were found across various exercise modalities, including running, cycling and resistance training. Findings were demonstrated in human and animal studies, and were found in individuals with and without pre-existing health conditions, including mental and metabolic health. This study also highlighted that disruptions in eCB signaling have been associated with a number of stress-related conditions, including anxiety, depression, PTSD, obesity, and diabetes.
The role of the ECS in the central nervous system is further supported by a 2024 review published in The Journal of Neural Regeneration Research, with a subsequent 2024 review demonstrating that the ECS interacts with glia-immune signaling to modulate neuroinflammation and sleep.
Stress, inflammation and sleep disturbances have all been shown to alter endocannabinoid signaling, supported by a previous 2017 review published in Neuropsychopharmacology Reviews. This study echoed the role exercise has in boosting endocannabinoid concentrations, contributing to the analgesic and mood-enhancing effects.
A 2023 review further underscored the effects of physical exercise on the ECS, suggesting that the euphoric feelings associated with “runner’s high” are induced from the mobilization of endocannabinoids. Moreover, exercise, through its effects on the ECS, has been shown to support and restore homeostasis in the body, particularly induced by stress. Exercise, therefore, emerges as a promising lifestyle approach for promoting health by positively influencing eCB signaling, in addition to its plethora of additional benefits.
Chronic stress has been shown to disrupt eCB signaling and dysregulation of the ECS has been linked to stress-related conditions—including mental and metabolic health—via inflammatory mechanisms. Given the ECS’s broad impact on regulating bodily functions, exercise serves as a valuable tool to modulate inflammation, metabolism and stress, helping to restore balance within this vital signaling system.
A previous 2014 study in The Annual Review of Neuroscience underscored the role of endocannabinoids relative to modulating stress, demonstrating the vastness and density of cannabinoid receptors in the brain, comparable to those of GABA and striatal dopamine receptors. A 2021 review published in Biological Psychiatry further examined the relationship between depression, anxiety, and the dysregulation of the endocannabinoid system (ECS), underscoring this relationship. The role of the ECS in the nervous system is further substantiated by a 2021 review published in Biological Psychiatry Cognitive Neuroscience and Neuroimaging, highlighting its role in synaptic function and plasticity.
Exercise, in addition to a healthy lifestyle, therefore can be supportive in terms of mitigating stress and modulating mental and physical aspects of health.
A 2021 study published in Gut Microbes explored the interaction between the endocannabinoid system and the gut microbiome induced by exercise in influencing inflammatory markers, gut microbiota, energy homeostasis, and immune function. The effects of endocannabinoid concentrations on gut microbiome composition were measured, including gut-metabolites: short-chain fatty acids (SCFAs), pro-inflammatory cytokines, TNF-α and IL-6 in two cohorts: a 6-week exercise intervention group and a control group, with a cross-sectional validation cohort.
Findings revealed that endocannabinoids were positively correlated with gut microbiome diversity and SCFA producing bacteria, such as butyrate, in addition to reductions in inflammation. These findings underscore the novel modulating effects of the endocannabinoid system in governing homeostasis in the body and mind.
In addition to exercise, age, genetic variants, stress, sleep, and nutrition all play roles in influencing ECS function. Being mindful of the factors in our control, such as the stress alleviating effects of exercise, are natural yet novel ways of supporting this regulatory system, integral to our health. Exercise emerges as not only an effective tool for improving physical and mental health, but as a powerful modulator of the ECS, influencing a wide array of homeostatic functions in the body and mind.
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