The role of the endocannabinoid system
What is the endocannabinoid system and why does a human have one?
Locations of the CB1 receptors
The cannabinoid CB1 receptors are primarily located on nerve cells in the brain, spinal cord, but they are also found in some peripheral organs and tissues such as the spleen, white blood cells, endocrine gland and parts of the reproductive, gastrointestinal and urinary tracts. (
Locations of the CB2 receptors
The cannabinoid receptor CB2 is not present in the central nervous system but mostly in tissues of the immune system. They have been found to be abundant throughout the body, such as in the intestines, spleen, liver, heart, kidneys, bones, blood vessels, lymphocytes, and reproductive organs. (S. Munro 1993)
The endocannabinoid system can be found at least:
- From mammals
- From birds
- From lizards
- From fish
Endo = Endogenic
The endocannabinoid system is so important that the U.S. Department of Health published a review that said the endocannabinoid system is associated with almost all human diseases 1. Indeed, the endocannabinoid system is one of the largest human receptor networks. It is one of the most important physiological systems in human health, and its receptors are found throughout the body, affecting almost all physiological processes in the body. 2, 3
A breakthrough in finding the endocannabinoid system was not made until the early 1990s, when Lisa Matsuda and her colleagues at the National Mental Health Center succeeded in determining a THC-sensitive receptor in the rat brain. Thus, the first cannabinoid receptor CB1 was discovered. 4
Subsequently, in 1993, the next cannabinoid receptor was discovered – as part of the immune system and nervous system. CB2 receptors have been found to be abundant throughout the body, including the intestine, spleen, liver, heart, kidneys, skeleton, blood vessels, lymphocytes, and reproductive organs. 5
Cannabinoids, terpenes and flavonoids naturally occurring in hemp act together and individually, directly or indirectly, to balance the endocannabinoid system. 6
The basic functions of the ECS: “relax, eat, sleep, forget and protect.”
The endocannabinoid system (ECS) is like a bridge between body and mind. By understanding it, one can begin to see the mechanism that affects brain function, physical health, and the treatment of disease. 2
The endocannabinoid system is a network of receptors known at least in mammals, birds, lizards and fish. 7. Research on endocannabinoids is young and constantly evolving. New and surprising discoveries appear regularly. Findings on the functions and evolution of the endocannabinoid system reveal new insights into how cannabinoids affect health and disease management. 8, s. 53
Cannabinoids act on the body by binding to the molecular receptors encoded by our genes. These cannabinoid-capturing receptors are proteins found on the surfaces of our cell membranes. Because cannabinoids bind to receptors in the form of cannabinoids, they are called cannabinoid receptors. 8, s. 53
How does the endocannabinoidsystem system work?
The endocannabinoid system acts holistically in the body in a number of different ways. It is involved in the regulation of pain, appetite, metabolism, emotional states, memory, and sleep-wake rhythm. The endocannabinoid system includes CB1 and CB2 cannabinoid receptors, as well as other already known and as yet unknown receptors. It is also associated with the endorphin system, as well as the release of various neurotransmitters in neurons. In addition, there are so-called endocannabinoids in the body, the best known of which are anandamide and 2-AG. 8, s. 54
Where are CB1 and CB2 receptors located in the body?
The CB1 and CB2 receptors of the endocannabinoid system are found in almost every part of the body. CB1 receptors are particularly found in the brain and central nervous system.
G-protein receptors are the broadest class of receptors in the body – there are more than 1,000 different people in humans. Indeed, 30-50% of all modern drugs act on these receptors. (9 10, 3). The most common g-protein receptor in the brain is the cannabinoid receptor CB1, which is about 10 times the amount of other g-protein receptors.10.
CB2 receptors are found most in the immune system. Different receptors and related cannabinoids and the like have different functions and effects in the body. 8, s. 54.
Indeed, the endocannabinoid system affects the body in a multidimensional way by regulating the central nervous system and the immune system. The functioning of the system can both accelerate and slow down physiological functions. The psychological effects of cannabinoids in hemp and the body are due to CB1 receptors. The effects of CB2 receptors are even more physiological. (11, 8)
How can the endocannabinoid system be affected?
The endocannabinoid system can be affected by the addition of exogenous, i.e., external, cannabinoids associated with their receiving cannabinoid receptors, or by the activation of endocannabinoid cleavage enzymes. 12. In addition, the balance of endocannabinoids can be affected by exercise. 13.
Based on the latest research, Ethan Russo, a neurologist and research and development director at the International Cannabis and Cannabinoid Institute (ICCI), and many other researchers in the field theorized that the endocannabinoid system is designed to maintain balance in the body’s systems by slowing down and accelerating processes as needed. 14. According to him, many diseases are caused by deficiencies in the endocannabinoid system. 15.
Cannabinoid receptors and cannabinoids acting on it
THC, or tetrahydrocannabinol, was discovered by the ancestor of cannabinoid researchers, Raphael Mechoulam, along with his research team. THC is one of the most important cannabinoids for the discovery of the entire endocannabinoid system, as it also led to the discovery of cannabinoid receptors and endocannabinoids. 18. Regular use of THC can cause imbalances in the endocannabinoid system. 21
Raphael Mechoulam discovered the first intracorporeal cannabinoid with his research team. 19
- Pacher P. and Kunos G. 2013. Modulating the endocannabinoid system in human health and disease: successes and failures https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684164/. Viitattu 12.5.2018
- Alger, B. E. 2013. Getting High on the Endocannabinoid System. Cerebrum. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/. Viitattu 12.5.2018
- Russo, E. Introduction to the Endocannabinoid System. PHYTECS. https://www.phytecs.com/wp-content/uploads/2015/02/Russo-Introduction-to-the-Endocannabinoid-System-corr-January-2015.pdf
- Matsuda, L. A. ym. 1990. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. https://www.nature.com/articles/346561a0.
- Sean Munro, Kerrie L. Thomas & Muna Abu-Shaar. 1993. Molecular characterization of a peripheral receptor for cannabinoids. Nature. https://www.nature.com/articles/365061a0.
- E. Russo ja J. McPartland. 2001. Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts? Journal of Cannabis Therapeutics. https://www.researchgate.net/publication/228897917_Cannabis_and_cannabis_extracts_Greater_than_the_sum_of_their_parts. Viitattu 12.5.2018
- McPartland, JM.; Agraval, J.; Gleeson, D.; Heasman, K; Glass M. 2006. Cannabinoid receptors in invertebrates. 366-373. European Societey for Evolutionary Biology. https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1420-9101.2005.01028.x . Viitattu 12.5.2018
- Holland, J. 2010. Endocannabinoid System. The Pot Book. https://www.amazon.com/Pot-Book-Complete-Guide-Cannabis/dp/1594773688
- Tsai, W.. 2014. G Protein Coupled Receptors. Khan Academy. https://www.khanacademy.org/test-prep/mcat/organ-systems/biosignaling/v/g-protein-coupled-receptors.
- Cinar, R. ja Szücs, M. 2009. CB1 Receptor-Independent Actions of SR141716 on G-Protein Signaling: Coapplication with the μ-Opioid Agonist Tyr-d-Ala-Gly-(NMe)Phe-Gly-ol Unmasks Novel, Pertussis Toxin-Insensitive Opioid Signaling in μ-Opioid Receptor-Chinese Hamster Ovary Cells. Journal of Pharmacology and Experimental Therapeutics. https://www.ncbi.nlm.nih.gov/pubmed/19448142. Viitattu 12.5.2018
- Pacher, P. ym. 2006. The Endocannabinoid System as an Emerging Target of Pharmacotherapy. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2241751/
- Huttunen, R. 2016. Kipu ja endokannabinoidijärjestelmä. Oulun Yliopisto. Biokemian ja molekyylilääketieteen tiedekunta. http://jultika.oulu.fi/files/nbnfioulu-201702101163.pdf. Viitattu 22.4. 2018.
- Dietrich, A. ym. 2004 Endocannabinoids and exercise. British Journal of Sports and Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1724924/
- Russo, E. B. 2015. Introduction to the Endocannabinoid System. Phytecs. https://www.phytecs.com/wp-content/uploads/2015/02/IntroductionECS.pdf. Viitattu 19.4.2018
- Russo, E. 2016. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis and Cannabinoid Research. https://www.ncbi.nlm.nih.gov/pubmed/28861491
- Wood, T. B. ym. 1896. Cannabinol Part I. Journal of the Chemical Society. https://archive.org/stream/journalchemical10britgoog/journalchemical10britgoog_djvu.txt
- Adams, R.; Hunt, M. ja Clark, J. H. 1940. Structure of Cannabidiol, a Product Isolated from the Marihuana Extract of Minnesota Wild Hemp. https://drive.google.com/file/d/0B8fn7XCE0Wf4NjNZeTc0R2c4Q0k/view
- Y. Gaoni, and R. Mechoulam. 1964. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish. Journal of the American Chemical Society. https://echoconnection.org/discovery-endocannabinoid-system/
- Mechoulam, R. 1992. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. https://www.ncbi.nlm.nih.gov/pubmed/1470919
- Mechoulam, R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, Pertwee RG, Griffine G, Bayewitch M, Barg J & Vogel Z. 1995. Identification of an endogenous 2-monoglyceride, present in canine gut, thatbinds to cannabinoid receptors. Biochemical Pharmacology. 50: 83−90. https://www.researchgate.net/publication/222497387_Mechoulam_R_Ben-Shabat_S_Hanus_L_Ligumsky_M_Kaminski_NE_Schatz_AR_Gopher_A_Almog_S_Martin_BR_Compton_DR_Pertwee_RG_Griffine_G_Bayewitch_M_Barg_J_Vogel_ZIdentification_of_an_endogenous_2-monoglyceride_
- D. C. D’Souza ym. 2016. Rapid Changes in CB1 Receptor Availability in Cannabis Dependent Males after Abstinence from Cannabis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742341/