The Endocannabinoid System.

February 21, 2019

Did you know that humans have a system that produces cannabis-like compounds and regulates how cannabinoids like cannabidiol (CBD) interact with the body? This is the mechanism that explains how CBD may offer therapeutic effects.1

The endocannabinoid system (ECS) is a complex molecular system that functions primarily to maintain homeostasis in the body and regulate numerous physiological processes.2 The ECS has been proven to modulate functions in the central nervous system, immune system, endocrine system, cardiovascular system, and reproductive system.3 Scientists only discovered the ECS in 1990, so they are still learning about how it works and how CBD affects it. Here’s what research has revealed so far.4

 There are three essential components that make up theECS—endocannabinoids, receptors, and enzymes:

 1. Endocannabinoids are lipids produced throughout the body that are similar to phytocannabinoids, the active chemical compounds found in the Cannabis sativa plant. Researchers have discovered two of these cannabis-mimicking substances, anandamide (AEA) and 2-arachidonoylglyerol (2-AG), that like neurotransmitters send signals to receptors to work together and maintain balance in the body.5

2.  Endocannabinoid receptors are G-protein coupled receptors found mainly in the central nervous system and peripheral nervous system. Endocannabinoids bind toCB1 and CB2 receptors to signal that the ECS needs to begin maintaining homeostasis in response to a change, such as stress, inflammation, or pain.

3. Enzymes are needed in the ECS to break down endocannabinoids after they’ve communicated with the receptors and carried out their intended function. The two enzymes involved are fatty acid amide hydrolase to synthesize AEA and monoacylglycerol acidlipase to break down 2-AG. 6

Both endocannabinoids and their receptors do their jobs throughout the body—in the brain, skin, bone, fatty tissue, immune cells, liver, pancreas, skeletal muscle, heart, blood vessels, kidney, and gastrointestinal tract.7 The entire endocannabinoid system is involved in numerous bodily functions, including pain, the immune system, inflammation, motor control, memory, mood, appetite, stress, sleep, metabolism, the cardiovascular system, muscle formation, bone growth, liver, nerves, and the reproductive system.6,8,9

How CBD and THCAffect the ECS

Tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis, binds to both CB1 and CB2 receptors in the ECS just as endocannabinoids do. This results in both positive (no pain, increased appetite) and negative effects (anxiety, paranoia) on the body and mind.10

Researchers are still investigating the mechanisms that explain how CBD, the non-psychoactive compound in cannabis, interacts with theECS. Studies show that CBD doesn’t bind to CB1 or CB2 receptors in the same wayas THC.11 One study found that CBD stimulates the endocannabinoid system by enhancing the signaling that the endocannabinoid anandamide sends to the receptors. This results in boosting homeostasis in the body and lessening pain and inflammation without side effects.12

For more research on the therapeutic uses of CBD for inflammation, pain, anxiety, insomnia, nausea, stress, epilepsy, and more conditions, see “Cannabinoids: CBD vs. THC.”

 Footnotes:

1. UCLA Health; https://www.uclahealth.org/cannabis/human-endocannabinoid-system

2. Perry G. Fine, M.D., “The EndocannabinoidSystem, Cannabinoids, and Pain,” Rambam Maimonides Med J (October 2013). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820295/

3. Komorowski J, “The Role of the Endocannabinoid System in the Regulation of Endocrine Function and in theControl of Energy Balance in Humans,” Postepy Hig Med Dosw (2007): 99-105.

4. Lisa A. Matsuda, “Structure of aCannabinoid Receptor and Functional expression of the Cloned cDNA,” Nature (August 1990): 561–564

https://www.nature.com/articles/346561a0

5. RG Pertwee, "The Pharmacology ofCannabinoid Receptors and Their Ligands: An Overview," International Journal of Obesity (April2006): S13–8.

https://www.ncbi.nlm.nih.gov/pubmed/16570099

6. Shenglong Zou, “Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central NervousSystem,” Int J Mol Sci. (March 2018):833. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/

7. Mackie K., “Cannabinoid Receptors: WhereThey Are and What They Do,” JNeuroendocrinol (2008): 10-14.

https://www.ncbi.nlm.nih.gov/pubmed/18426493

8. Alger BE., “Getting High on the Endocannabinoid System.” Cerebrum(November-December 2013): 14.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/

9. Maccarrone M, “Endocannabinoid Signaling at the Periphery: 50 Years After THC,”Trends Pharmacol Sci. (May 2015): 277-296.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420685/

10. Zerrin Atakan, “Cannabis, A Complex Plant:Different Compounds and Different Effects on Individuals,” Ther Adv Psychopharmacol. (December 2012): 241–254.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736954/

11. Wei Xiong, “Cannabinoids SuppressInflammatory and Neuropathic Pain by Targeting α3 Glycine Receptors,” J Exp Med. (June 2012): 1121–1134.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371734/

12. Leweke FM, “Cannabidiol EnhancesAnandamide Signaling and Alleviates Psychotic Symptoms of Schizophrenia,” Transl Psychiatry. (March 2012).

https://www.ncbi.nlm.nih.gov/pubmed/22832859/

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