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Human Endocannabinoid System RESOURCES FOR HEALTH CARE PROVIDERS Human Endocannabinoid System How Cannabis interacts with the body The human endocannabinoid system (ECS) is a widespread regulatory system in the human body that affects various functions and processes such as feelings, moods, pain, appetite, sleep, memory, stress response, metabolism, and immune function. [1] The Purpose of the Human Endocannabinoid b. CB2 (Cannabinoid receptor type 2) is found System predominantly in the peripheral nervous system, The ECS regulates a number of physiological functions especially in immune cells. Possible expression in the and facilitates the relationship between different central nervous system is being researched. These neurotransmitter systems, ultimately being a key receptors play a role in pain modulation, inflam- player in the control of behavioural responses. [2] mation and immune response to pathogens. [6] If there is an effect to the body or a function that needs 3. Enzymes: These substances help to activate and to happen, such as pain from an injury or a fever, the break down endocannabinoids once they have ECS is activated to restore biological harmony and bring completed their function. [1,4] the body back to its normal state (homeostasis), i.e., Endocannabinoids bind to the receptors to activate going from a stressful situation to a relaxed state. [3] the ECS response. When these combine, there is a response in the body, and depending on what is needed, How does the ECS work? there will be an impact on immunity, sensation, mood, The ECS involves three core components: and even consciousness. This is when the body is endocannabinoids, receptors, and enzymes. [2,4] alerted, needing help returning to its normal state. 1. Endocannabinoids: These are substances made For example: by the body. Two key endocannabinoids have been In response to stress, there extensively researched: [5] is an increase in cortisol which results in fight or a. Anandamide (AEA) STRESS flight response in the body. b. 2-arachidonoyl glycerol (2-AG) At the same time, endocan- These are messengers of the ECS and bind to the nabinoids are produced. receptors to produce their effects. [4] Through this response, ENDOCANNABINOID 2. Receptors: These are present throughout the endocannabinoids bind to brain and body. There are two types of these ‘main the ECS receptors to begin message-receivers’ [2]: restoring the body to a balanced state. [2] a. CB1 (Cannabinoid receptor type 1) is abundant REDUCTION Image courtesy of Ruth Ross’s in the central nervous system but also found in IN STRESS presentation – Demystifying the low concentration in various peripheral tissues. Endocannabinoid System. [1] ECS and Cannabis References and further reading In the 1990’s, scientists discovered endocannabinoids [1] Ross, R. (2019). Demystifying the endocannabinoid the natural cannabis-like molecules produced in the system. TEDxMississauga. body, such as anandamide. Scientists began to realize https://www.youtube.com/watch?v=8GsmTFytBYI cannabis exerted its effects, in part, by mimicking our [2] Navarrete, F., García-Gutiérrez, M. S., Jurado-Barba, endocannabinoids. [7] R., Rubio, G., Gasparyan, A., Austrich-Olivares, THC (Delta-9-tetrahydracannabinol): The interactions A., & Manzanares, J. (2020). Endocannabinoid of THC (the intoxicating component of cannabis) with System Components as Potential Biomarkers the ECS are potentially complex. [5] Many of the effects in Psychiatry. Frontiers in Psychiatry, 11(315). of THC are similar to that of endocannabinoids: [7] https://www.frontiersin.org/articles/10.3389/fp- n Hunger: syt.2020.00315/full • During states of fasting or long periods of not [3] Dr. Sealey, R. (2019, November). Polypharmacy, eating, endocannabinoids are released in the seniors and medical cannabis — a possible solution. brain activating CB1 receptors which alerts the BC Cares Providers Association. brain of hunger. https://bccare.ca/2019/11/polypharmacy-se- • Similarly, when THC is consumed, it activates niors-and-medical-cannabis-a-possible-solution/ CB1 receptors tricking the brain to think there [4] Zou, S., & Kumar, U. (2018). Cannabinoid Receptors have been long periods of fasting, commonly and the Endocannabinoid System: Signaling and known as “having the munchies”. Function in the Central Nervous System. International n Stress/Anxiety: Journal of Molecular Sciences, 19(3), 833. https:// • In response to stress or anxiety, endocannabi- doi.org/10.3390/ijms19030833 noids are released in the brain to help restore [5] Lu, H. C., & Mackie, K. (2016). An Introduction to normal function. Similarly, THC activates the the Endogenous Cannabinoid System. Biological endocannabinoid receptors, producing an effect psychiatry, 79(7), 516-525. of relaxation. In some cases, however, THC may https://doi.org/10.1016/j.biopsych.2015.07.028 cause paranoia and anxiety. n Pain: [6] Laurentiis, A., Araujo, H., & Rettori, V. (2014). Role • In response to pain stimuli, endocannabinoids of the Endocannabinoid System in the Neuro- are released in order to create a temporary endocrine Responses to Inflammation.Current analgesic effect, similar to endorphins. Pharmaceutical Design, 20, 000-000. https://pdfs.semanticscholar.org/bad0/4f2f9f- CBD (Cannabidiol): Research is being conducted to f564a6348c11cbe33e4f508151df30.pdf understand how CBD (cannabidiol: non-intoxicating [7] Healthline. (2019). A simple guide to the Endocan- component of cannabis) interacts with the ECS. [7] nabinoid System. https://www.healthline.com/ n CBD has a low affinity for both CB1 and CB2 health/endocannabinoid-system#thc receptors. [8] Fine, P. G., & Rosenfeld, M. J. (2013). The endocan- n CBD studies have shown that CBD can be active nabinoid system, cannabinoids, and pain. Rambam at CB2 receptors, through which it exerts anti- Maimonides medical journal, 4(4). inflammatory effects. [8] https://doi.org/10.5041/RMMJ.10129 In the spirit of Two-Eyed Seeing (Martin, 2012), this fact sheet reflects multiple ways of knowing and incorporates scientific literature, grey literature and Indigenous ways of knowing, such as storytelling, beliefs, values and practices. Every attempt has been made to review and provide best practice research, evidence and information on the use of cannabis. Each fact sheet has gone through a thorough peer review. References and sources are numbered and listed both inline and at the bottom of every fact sheet. Martin D. (2012) Two-eyed seeing: A framework for understanding Indigenous and non-Indigenous approaches to Indigenous health research. Canadian Journal of Nursing Research, 44(2): 20-42. PMid:22894005.
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