Biochemistry for people in a hurry
In 1964, THC (tetrahydrocannabinol) was identified as the psychoactive chemical in marijuana responsible for making users “high.”1,2 Nearly thirty years later, in trying to figure out how it made the user high, the Endocannabinoid System (ECS) was discovered.3,4
Although its founding and name are derived from the cannabinoid THC, it has existed for over 600 million years, well before the marijuana plant, and is found in most animals – mammals, amphibians, reptiles, birds, insects and invertebrates such as the sea squirt.5
It works like this: every cell within the body is enclosed in a membrane that protects it from the environment. This membrane has “doors” (receptors) that allow certain chemicals in while keeping others out – things like nutrients, hormones, salt, sugar. These are shaped in such a way that like a key, they can unlock the door (bind to the receptor) and enter the cell. This caused a series of reactions that makes the cells do very specific things – from controlling blood sugar and body temperature, to stopping pain.6
The ECS has doors that enter into the majority of the 37 trillion cells in the human body – the brain, organs, connective tissues, glands, and immune cells7 – and are the most abundant receptor in the brain.8 Because of this, the ECS acts as the master “communication system” in the body. It affects every system and exerts overall control of the body’s functions, maintenance, and balance (homeostasis).9
For example, when you are bitten by a mosquito, specific receptors on skin cells cause the generation of a chemical message that travels thru the nerve circuitry to the brain which in turns, responds with a chemical message that registers the pain and tells you to scratch. Your body is “out of balance.”10
At the same time, the ECS signals the release of chemicals that decreases the sensations of pain (the itch), stabilizes the nerve cells and signals the immune cells to stop the ensuing inflammation. Your body is back in balance – regulated by the ECS.11-13
Similarly, in eating, digestion releases glucose signaling the pancreas to produce insulin allows glucose into the cell for energy and controls blood sugar.14 At the same time, ECS receptors on those pancreatic cells play a role in this regulation – and are now being targeted for possible treatments of both Type 2 diabetes and obesity.15-19
There are two known types of ECS receptors (so two different types of doors) – CB Type-1 (CB1) and Type-2 (CB2). While both are found throughout the body, the CB1 doors are more concentrated in the brain and central nervous system while CB2 in the immune, gastrointestinal and peripheral nervous systems.20-21 However, new research has shown that there are many more types and that both endo- and phytocannabinoids affect them.22-24
This is why the ECS is considered a master communications system: with so many receptors throughout the body, it affects multiple systems and plays multiple roles in key aspects of everyday functioning and health. As of this writing, these include but are not limited to:
|Appetite, Digestion, Hunger||Mood|
|Cardiac Function/Circulation||Motor Control|
To date, there are only two known endocannabinoids (produced by the body). However, recently several new phytocannabinoids – unrelated to THC or the hemp plant – have been discovered opening up new avenues for potential therapies.25
Therefore, with the current research focus and new findings, it is expected that the ECS plays a much a larger role than that our current understanding.
- Mechoulam R, Gaoni Y: A total synthesis of dl-delta-1-tetrahydrocannabinol, the active constituent of hashish. J Am Chem Soc. 1965. 87:3273-75.
- Mechoulam R, Shani A, Edery H et al.: Chemical basis of hashish activity. Science 1970, 169(3945):611-2
- Di Marzo V, Bifulco M, De Petrocellis L: The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov. 2004. 3(9):771-84.
- Alger B: Getting High on the Endocannabinoid System. Cerebrum. 2013. 14.
- McPartland J, Pruitt P: Sourcing the Code: Searching for the Evolutionary Origins of Cannabinoid Receptors, Vanilloid Receptors, and Anandamide. J Cannabis Ther. 2002. 2(1):73-103.
- O’Connor, C. M. & Adams, J. U. Essentials of Cell Biology. Unit 3. Cambridge, MA: NPG Education, 2010.
- Bianconi E, Piovesan A, Facchin F et al: An estimation of the number of cells in the human body. Ann Hum Biol. 2013. 40(6): 463–471.
- Chiarlone A, Bellocchio L, Blázquez C et al: A restricted population of CB1 cannabinoid receptors with neuroprotective activity. Proc Natl Acad Sci U S A. 2014. 111(22):8257-62.
- Sallaberry C, Astern L: The Endocannabinoid System, Our Universal Regulator. J Young Inv. 2018. 34(6):48-55.
- Jeffry J, Kim S, Chen Z-F: Itch Signaling in the Nervous System. Physiology (Bethesda, Md). 2011. 26(4):286-292.
- Lee S: Molecular Mechanisms of Itch and Pain: An Overview. Itch & Pain. 2015. 2: e554.
- Mounessa J, Siegel J, Dunnick C et al: The role of cannabinoids in dermatology. J Am Acad Dermatol. 2017. 77(1):188-190.
- Bíró T, Tóth B, Haskó G et al: The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends in Pharm Sci. 2009. 30(8):411-420.
- Sonksen P, Sonksen J: Insulin: understanding its action in health and disease. Br J Anaesth. 2000. 85(1):69-79.
- Ziv E, Weiss L, Raz I et al: Islet protection and amelioration of diabetes type 2 in Psammomys obesus by treatment with cannabidiol. J Diab Mellit 2012. 2(1):27-34.
- Gruden G, Barutta F, Kunos G et al.: Role of the endocannabinoid system in diabetes and diabetic complications. Br J Pharmacol 2016, 173(7):1116-27.
- Scherer T, Buettner C: The dysregulation of the endocannabinoid system in diabesity – a tricky problem. J Mol Med (Berl). 2009. 87(7): 663–668.
- Horn H, Böhme B, Dietrich L et al: Endocannabinoids in Body Weight Control. Pharmaceuticals. 2018. 11, 55.
- Watkins B, Kim J: The endocannabinoid system: directing eating behavior and macronutrient metabolism. Front. Psychol. 2015. 5:1506.
- Bow EW, Rimoldi JM: The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation. Perspect Medicin Chem 2016, 8:17-39.
- Pertwee RG: The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 2008, 153(2):199-215.
- Qiao Z, Kumar A, Kumar P et al.: Involvement of a non-CB1/CB2 cannabinoid receptor in the aqueous humor outflow-enhancing effects of abnormal-cannabidiol. Exp Eye Res 2012, 100:59-64.
- Jarai Z, Wagner JA, Varga K et al.: Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proc Natl Acad Sci U S A 1999, 96(24):14136-41.
- McHugh D, Tanner C, Mechoulam R et al.: Inhibition of human neutrophil chemotaxis by endogenous cannabinoids and phytocannabinoids: evidence for a site distinct from CB1 and CB2. Mol Pharmacol 2008, 73(2):441-50.
- Gertsch J, Pertwee R, Di Marzo V: Phytocannabinoids beyond the Cannabis plant – do they exist? British Journal of Pharmacology. 2010. 160(3):523-529.