By Alice de Bernardy
*article written in June, 2022
It has widely been shown that exercise improves the mood and makes people “happy”.1 Exercise can result in beneficial outcomes such as raising the level of confidence, taking part in a social activity, and achieving objectives. However, during exercise, one might experience a particular “flow” reaching its peak when running during the commonly called “runner’s high”. The neuroscience behind this phenomena still raises questions. Runner’s high is described as an experience of euphory and well-being during running, transcending the barriers of time and space. Everything feels easier and time seems distorted.2
First attempts to underpin the neurological process behind a runner’s high led to the “Endorphin hypothesis”.3One of the main roles of endorphin is to mediate pain sensations and induce a feeling of happiness by binding to opioids receptors in the brain. Studies concluded that the rise in endorphins following exercise mediated the analgesic effects of exercise, potentially linked to a rise of ß-endorphin circulation in plasma.4 However, this hypothesis has been widely refuted. One of the main arguments being that due to its properties, ß-endorphins can’t cross the Blood Brain Barrier (BBB). Hence a change in peripheral ß-endorphin circulation does not allow any extrapolation on any central effect of the hormone.3
Further research suggested that endocannabinoids (eCB) played a role in the feeling associated with runner’s high. Indeed, several studies reported a rise in circulating eCB after exercise.2,5The endocannabinoid system is comprised of eCB such as anandamide, cannabinoids receptors (CB) and the enzymes for cannabinoid degradation.6 Two receptors have been identified; CB1 and CB2. CB2, located mainly on peripheral tissues is not believed to play a major role in the analgesic effects of the runner’s high.2 CB1 however, is expressed in both the peripheral and central nervous systems (PNS, CNS) on nerve terminals such as pain sensing fibers. Peripherally, CB1 can also be found in epithelial, muscle and lung tissues. CB1 and CB2 are both coupled to G-proteins and downstream inhibit adenylate cyclase which causes neuronal inhibition.2
While little is known on the stimuli leading to eCB secretion, evidence does suggest that eCB may mediate pain perception.2 This has been observed experimentally in mice, where the mice expressing CB1 kept running on a warming plate for longer that mice with CB1 blockage.7 By monitoring eCB levels, JSPQUI observed that running increased the level of circulating eCB, contributing to a decrease in pain sensation, proving both the potential role of eCB in runner’s high and the analgesic effects of eCB.
Later evidence showed that exercise led an increase in circulating anandamide in endurance athletes. 5Endocannabinoids, unlike endorphins, can cross the BBB due to their lipid composition. Therefore, an increased secretion of eCB peripherally can lead to a central action of eCB.3
Endocannabinoid receptor activation might also have other effects besides reducing centrally the pain perception during exercise. While the feeling of “flow” can be achieved via many different exercises or non-exercise-related activities, the feeling of runner’s high seems to be limited to running. For example, no record of swimmer’s high are known.2
This could be due to the fact that CB1 is expressed in cells peripherally, such as in the skin. The pain caused by long-distance running on the foot could stimulate eCB secretion. Since for example, swimming doesn’t induce the same level of pain on the epithelium this could explain the specificity of runner’s high to running.2On another level, cannabinoids have been reported to act as vasodilator, facilitating blood flow during exercise. Finally, eCB receptors are also expressed in the lung and, since cannabinoids have been reported to act as bronchodilators, it suggests that eCB could help facilitating breathing during exercise.2
To sum up, exercise stimulates eCB secretion to adapt the body to exercise. Several roles in physiological adaptation are suggested: facilitating blood flow, breathing, and inhibiting signals of pain. Since eCB can cross the BBB, their central action can explain the feeling of euphoria experienced by runners.
Interestingly enough, endocannabinoids and exogenous cannabinoids bind in a similar manner to cannabinoid receptors. Exogenous cannabinoids such as THC, the psychoactive biomolecule in marijuana, binds centrally to CB1 causing the feeling of euphoria.2
The feelings associated with runner’s high correlate with the effects of exogenous cannabinoids such as a state of introspection, wellbeing and mental sedation post-training, reduction in anxiety and time distortion.2
Similarity in endogenous and exogenous cannabinoids action are supported by evidence that both cannabinoids induce a release of dopamine in the Nucleus Accumbens, part of the brain involved in the reward circuit and addiction. This offers a first explanation for exercise addiction.2
In conclusion, though exercise leads to many physiological changes and the release of many different hormones leading to a feeling of happiness. The role of endorphins has been proven to be minimal and endocannabinoids are believed to be the main agent accounting to the feeling of runner’s high.
1. Roeh A, Lembeck M, Papazova I, Pross B, Hansbauer M, Schoenfeld J, et al. Marathon running improves mood and negative affect. J Psychiatr Res. 2020;130:254–9.
2. Dietrich A, McDaniel WF. Endocannabinoids and exercise. Br J Sports Med. 2004;38(5):536–41.
3. Szabo A, Griffiths MD, Demetrovics Z. Psychology and Exercise. In: Nutrition and Enhanced Sports Performance. Elsevier; 2013. p. 65–73.
4. Farrell PA, Gates WK, Maksud MG, Morgan WP. Increases in plasma beta-endorphin/beta-lipotropin immunoreactivity after treadmill running in humans. J Appl Physiol. 1982;52(5):1245–9.
5. Hillard CJ. Circulating endocannabinoids: From whence do they come and where are they going? Neuropsychopharmacology. 2018;43(1):155–72.
6. Stone NL, Millar SA, Herrod PJJ, Barrett DA, Ortori CA, Mellon VA, et al. An analysis of endocannabinoid concentrations and mood following singing and exercise in healthy volunteers. Front Behav Neurosci. 2018;12:269.
7. Fuss J, Steinle J, Bindila L, Auer MK, Kirchherr H, Lutz B, et al. A runner’s high depends on cannabinoid receptors in mice. Proc Natl Acad Sci U S A. 2015;112(42):13105–8.