Motivation and emotion/Book/2022/Exercise and endocannabinoids

Exercise and endocannabinoids:
What is the relationship between exercise and the endocannabinoid system?



An exercise induced altered state of consciousness has long been appreciated by athletes. The effect has been well documented in literature and subjected to scientific investigation proving the positive effects exercise has on one’s health both mental and physiological.

Exercise is found to induce changes in mental status, particularly when feeling pain, anxiety, depression creating a sense of wellbeing[factual?].

Recent research has begun investigating the origins of this phenomenon and findings have been made that exercise increases the concentration of endogenous lipid-based retrograde neurotransmitters known as endocannabinoids (Kendall & Yudowski, 2016).

The endocannabinoid system is a critical part of regulating the emotional, cognitive, and physical homeostasis within the human body[factual?]. It is defined as a widespread neuro-modulatory system which plays a significant role in central nervous system (CNS), synaptic plasticity and recognising endogenous and environmental stimuli. It is also responsible for regulating mechanisms of food intake as well as lipid synthesis and turnover in the liver and adipose tissue as well as glucose metabolism in muscle cells (Lu & Mackie, 2015).

This chapter examines the relationships between exercise and the endocannabinoid system and explore theories such as runners high.

Focus questions:

  • What is the endocannabinoid system?
  • What is exercise and its benefits?
  • How does exercise affect the endocannabinoid system?


Exercise: running on a treadmill

Exercise is a subset of physical activity that is planned, structured, and repetitive and has as a final or an intermediate objective the improvement or maintenance of physical fitness (Caspersen, 1985). There's strong evidence that being physically active can help you lead a healthier and happier life[factual?]. People who exercise regularly have a lower risk of developing many health conditions such as heart disease, type 2 diabetes, stroke, some cancers, and mental illnesses such as depression and anxiety (Burton, 2004).

The physiological effects of exercise


In a study undertaken to measure the relationship between mental health and physical activity, the results indicated that exercise has a significant benefit to mental health (Burton, 2004). Exercise has a positive effect on mental health as it allows for a release of built-up energy and stress that accumulates and provides a sense of achievement and growth when they are able to go further than before[factual?].

The psychological effects of exercise


Exercise accompanies physical health as this type of activity promotes body longevity as it burns fat and keeps the body operating at a higher level as exercise helps the body prevent muscular skeletal diseases that occur as you age (Kerr, 2006).

The endocannabinoid system


The endocannabinoid system is a vital element in emotional, cognitive and physical homeostasis within the human body and their biosynthesis, metabolism, and transit that are involved in a variety of physiological processes, including pain, appetite, memory, inflammatory and immune responses[factual?].

It is defined as a widespread neuro-modulatory system that plays a significant role in central nervous system development, synaptic plasticity and recognising endogenous and environmental stimuli (Lu & Mackie, 2015).

Endocannabinoids are located throughout the entirety of the body, densely packed with their receptors (Alger,2013). Figure 1 displays the endocannabinoid system within the major brain regions. The endocannabinoid system is comprised of cannabinoid receptors, Cannabinoid receptor type 1 (CB1) and Cannabinoid receptor type 2 (CB2) (Battista, 2012).

Cannabinoid receptor type 1 (CB1)


CB1 receptors, which are mostly found in the central nervous system located in the neocortex, hippocampus, basal ganglia, amygdala, striatum, cerebellum, and hypothalamus. The function of these receptors are to mediate the psychoactive effects of cannabinoids (Hillard, 2014). They play a key role in learning and memory processes, executive functioning, decision-making, sensory and motor responsiveness, emotional reactions, as well as eating and other homeostatic processes.

A deficiency of CB1 receptors is associated with negative psychological effects like anhedonia, anxiety, and the persistence of negative memories (Hillard, 2014).

Cannabinoid receptor type 2 (CB2)


CB2 receptors are sometimes referred to as the peripheral cannabinoid receptor because of their largely peripheral expression in immune cells, including white blood cells.

CB2 receptors are often referred to as the peripheral cannabinoid receptor because of their location in the peripheral nervous system. CB2 receptors are expressed in the immune system and regulate the immune and inflammatory pathways (Alger, 2013).

1 CB2 transmitters are associated with the immune system? :


2 Endocannabinoids defined as a localised neuro-modulatory system? :


Exercise and endocannabinoids


The relationship between exercise the endocannabinoid system can best be explained through the theory of ‘Runners High’[factual?].

Before the discovery of opioids, exercise scientists tried to account for the analgesic and euphoric mental states with alterations in the catecholamines such as adrenaline[factual?]. With the discovery of an opioid receptor network and endogenous opioid peptides, an entirely different mechanism was proposed and now exercise induced changes in psychological functions are a direct consequence of alterations in endogenous opioid release of endocannabinoids (Charytoniuk et al., 2020).

Marusak 2021 studied was [grammar?] able to determine that it is the endocannabinoid system that is responsible to the effect of runners high as throughout her testing when the cannabinoid receptors were blocked, there was a reduction in the beneficial effects of exercise[Provide more detail].

During exercise an increase in circulating endocannabinoid concentration occurs[factual?]. This is referred to as runners high. This phenomenon places the person into a state of euphoria and well-being experienced after a long exercise[factual?]. Athletes have described it as feeling pure happiness, elation, a feeling of unity with one’s self and/or nature, endless peacefulness, inner harmony, boundless energy, and a reduction in pain sensation[factual?].

Additionally, the increase in endocannabinoid concentration from exercising is a key element in incrementing brain-derived neurotrophic factor mediating benefits in cognition, neurogenesis, plasticity synaptic, reduced anxiety, and antidepressant effects[factual?].

  Case study
Wired to run: exercise-induced endocannabinoid signalling in humans and cursorial mammals with implications for the ‘runner’s high’, (Raichlen, 2012)

10 recreationally fit humans were subjected to aerobic exercise on a treadmill. Running speed was selected to raise heart rate. Blood samples were collected by venipuncture before and after a period spent running on the treadmill and Psychological state was assessed before and after trials using a standard questionnaire that measured positive affect. The two recognized endocannabinoids, anandamide and 2-arachidonylglycerol showed a significant increase in levels within the subjects who exercised. These participants in the study also reported a more positive psychological assessment from the questionnaire. Thus, confirming the endocannabinoid hypothesis that exercise increases concentration on endocannabinoids[grammar?].

  Case study
A runner’s high depends on cannabinoid receptors in mice (Fuss,, 2015)

234 male mice were provided with running wheels to start with and to habituate them to wheel running. Mice ran, on average, 5.4 km per day. 2 days after the running wheels were blocked, half of the mice were assigned to running and the other half to a non-running. Runners were again subjected to a brief period of wheel running directly before behavioural testing and ran, on average, 6.5 - 0.7 km. When subsequently tested for anxiety-like behavior in a dark–light box test, the runner mice exhibited significantly less anxiety compared to those who were not exposed to exercise on the running wheel. The mice were then exposed to a hot plate to study pain sensitivity. The runner mice displayed an increased latency to lick hind paws or jump as a reaction to the heat, suggesting reduced thermal pain sensitivity. The mice that had participated in exercise on the running wheel prior to testing showed increased levels of endocannabinoids in blood cells. T his study on mice, demonstrated that cannabinoid receptors mediate acute anxiolysis and analgesia after running. Results displayed that anxiolysis depends on intact CB1 receptors on forebrain neurons and pain reduction on activation of peripheral CB1 and CB2 receptors. This demonstrates that the endocannabinoid system is crucial for two main aspects of a runner's high.



This chapter discussed the relationships between exercise and the endocannabinoid system. Across studies investigated within the case studies all data from results indicate that there is an increase in endocannabinoids as a result of exercise occurs. Thus, the relationship between exercise and the endocannabinoid system is that exercise induced endocannabinoid levels to increase and in return these endocannabinoids relay back positive physical and emotional effects on the athlete which in return encourages more exercise[factual?].

The endocannabinoid system is a vital part of maintaining one’s health both psychologically and physically thus further research into this topic is suggested. Currently there are some major gaps within the research. It isn’t yet clear what the minimum amount of exercise is to get a sufficient increase in endocannabinoids, and how long these compounds remain elevated after exercise as well as what types of exercise would produce the most endocannabinoids. Research into these topics would provide a better outline of how an individual should exercise to increase endocannabinoid circulation thus improving health.

Key takeaway - To achieve greater health, exercise is essential to implement into daily schedules.[vague]

See also


Motivation and emotion/Book/2020/Endocannabinoid system and emotion

The Endocannabinoid system


Alger, Bradley E. (2013-11-01). "Getting High on the Endocannabinoid System". Cerebrum: the Dana Forum on Brain Science 2013: 14. ISSN 1524-6205. PMID 24765232. PMC 3997295. 

Battista, Natalia; Di Tommaso, Monia; Bari, Monica; Maccarrone, Mauro (2012). "The endocannabinoid system: an overview". Frontiers in Behavioral Neuroscience 6. doi:10.3389/fnbeh.2012.00009. ISSN 1662-5153. PMID 22457644. PMC PMC3303140. 

Burton, Deborah Anne; Stokes, Keith; Hall, George M (2004-12-01). "Physiological effects of exercise". Continuing Education in Anaesthesia Critical Care & Pain 4 (6): 185–188. doi:10.1093/bjaceaccp/mkh050. ISSN 1743-1816. 

Caspersen, C J; Powell, K E; Christenson, G M (1985). "Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research.". Public Health Reports 100 (2): 126–131. ISSN 0033-3549. PMID 3920711. PMC 1424733. 

Charytoniuk, Tomasz; Zywno, Hubert; Konstantynowicz-Nowicka, Karolina; Berk, Klaudia; Bzdega, Wiktor; Chabowski, Adrian (2020-06-13). "Can Physical Activity Support the Endocannabinoid System in the Preventive and Therapeutic Approach to Neurological Disorders?". International Journal of Molecular Sciences 21 (12): 4221. doi:10.3390/ijms21124221. ISSN 1422-0067. PMID 32545780. PMC PMC7352563. 

Fuss, Johannes; Steinle, Jörg; Bindila, Laura; Auer, Matthias K.; Kirchherr, Hartmut; Lutz, Beat; Gass, Peter (2015-10-20). "A runner’s high depends on cannabinoid receptors in mice". Proceedings of the National Academy of Sciences 112 (42): 13105–13108. doi:10.1073/pnas.1514996112. ISSN 0027-8424. PMID 26438875. PMC PMC4620874. 

Hillard, Cecilia J. (2014-10-01). "Stress regulates endocannabinoid-CB1 receptor signaling". Seminars in Immunology. Making new connections: The intersection of neurendocrine and immune regulation 26 (5): 380–388. doi:10.1016/j.smim.2014.04.001. ISSN 1044-5323. PMID 24882055. PMC PMC4247817. 

Kendall, Debra A.; Yudowski, Guillermo A. (2017-01-04). "Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease". Frontiers in Cellular Neuroscience 10. doi:10.3389/fncel.2016.00294. ISSN 1662-5102. PMID 28101004. PMC PMC5209363. 

Kerr, John H.; Fujiyama, Hakuei; Sugano, Atsuko; Okamura, Taito; Chang, Milan; Onouha, Francis (2006-07-01). "Psychological responses to exercising in laboratory and natural environments". Psychology of Sport and Exercise 7 (4): 345–359. doi:10.1016/j.psychsport.2005.09.002. ISSN 1469-0292. 

Lu, Hui-Chen; Mackie, Ken (2016-04). "An Introduction to the Endogenous Cannabinoid System". Biological Psychiatry 79 (7): 516–525. doi:10.1016/j.biopsych.2015.07.028. PMID 26698193. PMC PMC4789136. 

Marusak, Hilary A. "The 'runner's high' may result from molecules called cannabinoids – the body's own version of THC and CBD". The Conversation. Retrieved 2022-10-17.

"Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the 'runner's high". doi:10.1242/jeb.063677. Retrieved 2022-10-17.


Endocannabinoids and mental health

What is the endocannabinoid system