Purpose of the endocannabinoid system
What is the endocannabinoid system and why does a human have one?
CB1 receptor locations
Cannabinoid receptor 1 (CB1) is located mainly in the central nervous system (forebrain, hippocampus, basal ganglia, cerebellum). CB1 receptors are also found in the prostate, uterus, testicles, small intestine, spleen, and lymphocytes. (W. Miller et al. 2002)
CB2 receptor locations
Cannabinoid receptor 2 (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 the gut, spleen, liver, heart, kidneys, bone, blood vessels, lymphocytes, and reproductive organs. (S. Munro 1993)
The internal cannabinoid system can be found at least:
- From mammals
- From birds
- From lizards
- From fish
Endo = internal
The endocannabinoid system is considered important, with the U.S. Department of Health publishing a review in which it said the endocannabinoid system is associated with almost all diseases in humans 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 the discovery of the endocannabinoid system was not made until the early 1990s, when Lisa Matsuda and her colleagues at the National Mental Health Center were able to determine THC receptor in the brain of rats. 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
Basic functions of the endocannabinoid system: “Relax, eat, sleep, forget and protect”
The endocannabinoid system 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 cannabinoid-shaped receptors, they are called cannabinoid receptors. 8, s. 53
How does the endocannabinoid 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 anandamides and 2-AG. 8, s. 54
Our endocannabinoid system forms a kind of protective network that, as part of our immune system and central nervous system, seeks to balance the function of the brain and other cells when they receive a signal of threat from outside or inside.
In general, the human body is made up of approx. Of the 30 trillion cells that make up an extensive, ever-adapting communications network. There are only brain cells. 100 billion, and the connections between them are calculated to be reached within more than the galaxies of the universe. Each of us is a sensitive biological machine made up of these cells. Each cell plays a unique role in the human physiological whole. The cells work together to create different tissues. The tissues, on the other hand, form organs and the organs together form you.
Each of these 30 trillion cells in your body is in constant contact with each other. Researchers call this signaling “cellular communication”. The endocannabinoid system is responsible for providing chemical feedback to these billions of communications. Cells communicate using signaling molecules known as ligands.
Ligands have specific binding sites known as receptors, which in turn receive signals. Depending on the signal and the receptor, the response is achieved in the receiving Sol, which forms the basis of cellular communication. The received message may initiate a chain reaction in the target cell, the effects of which vary depending on the situation.
Cellular communication strives for balance, or homeostasis. These homeostasis-seeking measures prevent body communication from tilting to either end or damaging body tissues and organs. Maintaining homeostasis is critical to the overall well-being of our bodies and individual organs.
We are made up almost entirely of cells, so the discovery of the endocannabinoid system and its overall impact on human health has been a very important finding for medicine. Each of our cells sends and receives thousands of signals every second to maintain our health.
Cells communicate their status to other cells, telling them whether they are in balance or not. The body responds to this to provide the ingredients needed for cell success. The endocannabinoid system provides a feedback system for this communication network. Clear cellular communication ensures efficient human functioning. It is responsible for coordinating immune responses, cell movement, and change. The feedback mediated by the cells and the endocannabinoid system is interpreted in the brain to elicit the required response. 9
Where are the CB1 and CB2 receptors of the endocannabinoid system found?
CB1 and CB2 receptors in 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. 10 11 , 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. 11 .
CB2 receptors, on the other hand, are found most in the immune system. Various receptors and related cannabinoids and the like. the compounds have different functions and effects in the body. 8 , s. 54.)
Indeed, the endocannabinoid system acts multidimensionally in the body 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.12 ,8
Endogenous cannabinoids or endocannabinoids
Nor does the endocannabinoid system consist of cannabinoid receptors alone. Endogenous cannabinoids, or endocannabinoids, maintain the balance of our body, or homeostasis. Homeostasis means a broader balance than just standing up. It means an appropriate balance of the physiological processes of the body. For example, 2-AG acts at the level of brain cells, securing their function e.g. head trauma.
Your body produces endocannabinoids as needed. The function of endocannabinoids has been linked to e.g. psychomotor movements, memory function, learning and thinking in general, neuroendocrine secretion, appetite, sensation of pain, nausea, and regulation of body temperature and immune system. 13
The role of endocannabinoids is so comprehensive in maintaining the health and basic functions of our body that the term clinical endocannabinoid deficiency has been suggested by renowned cannabinoid researcher and neurologist Ethan Russo. This deficiency may partly explain various conditions such as migraine, fibromyalgia or irritable bowel syndrome. 17. Our bodies can also produce too many endocannabinoids, in which case it is not a defect but rather some kind of imbalance. 13
How is the endocannabinoid system affected?
The endocannabinoid system can be affected by the addition of exogenous, i.e., external cannabinoids (by eating CBD products or drinking CBD-A hemp juice) associated with their receiving cannabinoid receptors, or by acting on enzymes involved in the cleavage of endocannabinoids. 14 . In addition, the balance of endocannabinoids can be affected by exercise 15 .
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 by slowing down and speeding up processes as needed. 16 . According to him, many diseases are caused by deficiencies in the endocannabinoid system 17 .
Cannabinoid receptors in the endocannabinoid system 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. 20. Regular use of THC can cause imbalances in the endocannabinoid system 21
Raphael Mechoulam also discovered the first intracorporeal cannabinoid with his research team 22
- 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/. Referred on 12.5.2018
- Algiers, BE 2013. Getting High on the Endocannabinoid System. Cerebrum. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/. Referred on 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 Referenced 22.4. 2018.
- Matsuda, LA et al. 1990. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. https://www.nature.com/articles/346561a0. Referenced 22.4. 2018.
- Sean Munro, Kerrie L. Thomas & Muna Abu-Shaar. 1993. Molecular characterization of a peripheral receptor for cannabinoids. Nature. https://www.nature.com/articles/365061a0. Referenced 22.4. 2018.
- E. Russo and 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. Referred on 12.5.2018
- McPartland, JM .; Agraval, J .; Gleeson, D .; Heasman, K; Glass M. 2006. Cannabinoid receptors in invertebrates. 366-373. European Society for Evolutionary Biology. https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1420-9101.2005.01028.x . Referred on 12.5.2018
- Holland, J. 2010. Endocannabinoid System. The Pot Book. https://www.amazon.com/Pot-Book-Complete-Guide-Cannabis/dp/1594773688 Referenced 22.4. 2018.
- Tasker C. 2021 The Canna-Manual: Cannabis in Context https://www.amazon.co.uk/Canna-Manual-Cannabis-Context-Christopher-Tasker-ebook/dp/B08WKGHJ71 Referred to 31.5.2021
- Tsai, W .. 2014. G Protein Coupled Receptors. Khan Academy. https://www.khanacademy.org/test-prep/mcat/organ-systems/biosignaling/v/g-protein-coupled-receptors. Referenced 22.4. 2018.
- Cinar, R. and 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. Referred on 12.5.2018
- Pacher, P. et al. 2006. The Endocannabinoid System as an Emerging Target of Pharmacotherapy. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2241751/
- Haspula D. and Clark M. 2020. Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases. https://pubmed.ncbi.nlm.nih.gov/33080916/ Referred to 31.5.2021
- Huttunen, R. 2016. Pain and endocannabinoid system. University of Oulu. Faculty of Biochemistry and Molecular Medicine. http://jultika.oulu.fi/files/nbnfioulu-201702101163.pdf. Referenced 22.4. 2018.
- Dietrich, A. et al. 2004 Endocannabinoids and exercise. British Journal of Sports and Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1724924/
- Russo, EB 2015. Introduction to the Endocannabinoid System. Phytecs. https://www.phytecs.com/wp-content/uploads/2015/02/IntroductionECS.pdf. Referred on 4/19/2018
- 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 Referenced 22.4. 2018.
- Wood, TB et al. 1896. Cannabinol Part I. Journal of the Chemical Society. https://archive.org/stream/journalchemical10britgoog/journalchemical10britgoog_djvu.txt Referenced 22.4. 2018.
- Adams, R .; Hunt, M. and Clark, JH 1940. Structure of Cannabidiol, a Product Isolated from the Marijuana Extract of Minnesota Wild Hemp. https://drive.google.com/file/d/0B8fn7XCE0Wf4NjNZeTc0R2c4Q0k/view Referenced 22.4. 2018.
- 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/ Referenced 22.4. 2018.
- DC D’Souza et al. 2016. Rapid Changes in CB1 Receptor Availability in Cannabis Dependent Males after Abstinence from Cannabis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742341/
- 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 Referenced 22.4. 2018.
- 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, that binds 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_ Referenced 22.4. 2018.