The endocannabinoid system is crucial for maintaining homeostasis (balance). As a result, cannabinoids influence everything from emotion and pain perception to metabolism, prenatal development, and the gut microbiome. The plant cannabinoid THC exerts its psychoactive effects through cannabinoid receptors in the brain. These receptors (CB1 receptors) are widespread in organs and tissues beyond the brain, including the lungs and cardiovascular system. As a result, we would expect that cannabinoids have some kind of relationship to physical activity and therefore a potential influence on exercise performance.
What is known about cannabinoids and physical activity? Let’s explore the following questions across three articles:
Part I: How & Why the Endocannabinoid System Responds to Physical Activity
Part III: How Body Fat & Exercise Influences THC levels in the Body.
The two major endogenous cannabinoids are anandamide and 2-AG. A number of clinical (human) and preclinical (animal) studies conducted since the 2010s looked at how acute (short-term) exercise affects endocannabinoid levels in the body. A 2022 meta-analysis looked at these to identify trends in the results.
There was a lot of variability in the results and design of studies, but it was generally found that anandamide levels acutely increase following exercise. This tendency was seen for different forms of exercise (e.g. running, cycling, resistance training), in both animals and humans, as well as human patients with and without preexisting conditions (e.g. PTSD, depression). The effects of acute exercise on 2-AG were much less consistent across studies, and there wasn’t enough data to assess the effects of chronic (long-term) exercise on endocannabinoid levels.
In animal studies, where biological mechanisms can be studied in detail, both voluntary exercise and palatable food consumption have similar effects on the endocannabinoid system. CB1 receptors in the brain are important for reward processing generally, and specific CB1 receptor-containing neurons are crucial for the rewarding effects of everything from drugs (including THC) to the motivation to engage in exercise. In the case of mice, exercise means wheel running–they love it. They also love sugar water.
If given the opportunity, mice spend quite a bit of time running on wheels and sipping sucrose–it’s rewarding to them. It has been shown that engaging in either behavior increases the sensitivity of CB1 receptors on specific neurons in the brain. After wheel running or sugar consumption, these receptors are more sensitive to cannabinoids–both exogenous cannabinoids (pharmaceutical drugs) and endogenous cannabinoids found naturally in the brain. This means that both an animal’s physical activity and dietary patterns can alter its sensitivity to cannabinoids.
Similar to what’s generally been observed in humans and other animals, mice experience an acute elevation in blood endocannabinoid levels following running wheel exercise. Human long-distance runners sometimes describe a “runner’s high,” a feeling of euphoria, lower anxiety, and analgesia (pain relief) from running. Something akin to this is also seen in mice. Behavioral analysis indicates that they experience anxiety- and pain-relief from wheel running. This “runner’s high” effect depends on CB1 receptors in specific neurons in the brain, and further illustrates the endocannabinoid system’s involvement in coordinated changes across the brain and body in response to physical activity.
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