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Biochemistry and CBD

by: Good Earth Natural Foods

Cannabidiol (CBD) and similar cannabinoid substances navigate through receptor sites found in the “endocannabinoid system” (ECS). This is a whole-body system dedicated just for cannabinoids! Cannabinoids may be generalized into two categories: internally made cannabinoids (endocannabinoids) and cannabinoids found in plants (phytocannabinoids). CBD is a phytocannabinoid found abundantly in the plant Cannabis sativa L., or industrial hemp (1). 

The ECS has influence over the appetite, pain and sensation centers, mood and memory centers, and the voluntary exercise area. “Runners high” is associated with the endocannabinoid “Anandamide” which is released after sustained rigorous exercise (2). Cannabinoids act on the ECS receptors either directly or indirectly to regulate and balance several functions. In studies, CBD has shown to be calming, pain-relieving, helpful in reducing convulsions and seizures, anxiety-reducing, anti-oxidant, anti-psychotic, and protective to the nervous system (3).

There are two known types of receptors: CB1 and CB2. CB1 receptors are found throughout the central and peripheral nervous systems (4). Although CB1’s are mostly in the brain, others are found in detoxification organs like the liver, kidneys, and lungs. CB1 receptors send signals that regulate senses. CB2 receptors work most closely with T lymphocytes, B lymphocytes, natural killer cells, and macrophages in the immune system (5). They can also affect gastrointestinal response and peripheral nervous system activity. 

CBD activates CB1 receptor cites by opening the door wide for all cannabinoids to bind to the receptor site and inhibiting other chemicals from getting in. In other words, CBD keeps the receptor sites working at optimal capacity to favor cannabinoids and detour other chemicals. This simply allows calming and soothing cannabinoids to rule the body while rejecting other chemicals, such as stress hormones. 

To explain the biochemistry, CBD acts as an “agonist”, “inverse agonist”, “antagonist” and “inhibitor” on different receptor sites in the body. An “agonist” binds to and activates a receptor, creating a change that can sometimes be felt in the body. An “inverse agonist” binds to a receptor but does the opposite of an agonist, causing it not to activate. An “antagonist”, often referred to as a “blocker,” binds to the receptor, blocks or dampens it, and causes it not to activate. An inhibitor simply interferes with or inhibits the entire chemical action at the receptor site, causing it not to activate (6).

CBD acts as an agonist that activates the 5-HT1A serotonin receptor site which contributes to a feeling of happiness and well-being. It also activates the TRPV1-2 vanilloid receptor, known to trigger or to reduce pain signals. CBD works by activating the receptor’s pain-reducing properties (7).  

CBD acts as an antagonist for alpha-1 adrenergic, which usually activates during “fight or flight” responses. CBD calms this stress reaction by blocking or dampening the response. CBD also antagonizes the µ-opioid receptor, a morphine receptor with addictive qualities. This is why CBD has been researched as one of the solutions for the opioid addiction epidemic (8).

CBD acts as an uptake inhibitor for noradrenaline, dopamine, serotonin, and gaminobutyric acid (GABA). This means these neurotransmitters become more saturated so they can more easily activate their receptor cites, which contributes even more to a sense of happiness, ease, and well-being. Likewise, CBD inhibits cellular uptake of “anandamide”, a chemical discussed earlier as being associated with euphoria (9). 

These indirect interactions of CBD with the ECS have many good stress-reducing effects. Some of CBD’s functions include:

-Acts as an “inverse agonist” of CB2 receptors.  This helps CBD antagonize psychoactive cannabinoids like CP55940 and THC at the receptor site. This likewise plays a role in CBD’s anti-addictive and anti-inflammatory properties. (10)

-Effectively increases CB1 density, amplifying the effects of all cannabinoids that bind to CB1 receptors.

-Acts at a 5-HT 1a receptor agonist in the brain, meaning that CBD has calming and soothing effects such as some potent analgesics (without side-effects).

-Acts as an “inverse agonist” of CB2 receptors (a chemical that binds to the same receptor as agonists but produce the exact opposite result). This means it effectively reduces the effects of cannabinoids that make CB2 less responsive.

-Acts as an antagonist for the putative GPR55 receptor (an element of the ECS that is still being researched to find out if it is a third type of cannabinoid receptor). 

-“Acts on mitochondria Ca2 stores, blocks low-voltage-activated (T-type) Ca2 channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH) [A31555, A31574].” This property of CBD is related to it’s anti-seizure properties. (3) (11) -“antineoplastic and chemopreventive activities.” (3) CBD boosts just about every function of our cannabinoid receptors! All biochemistry aside, CBD is “out of this world” for its potential effects of soothing and relaxing the body!

 

 

References:

CV Sciences marketing pamphlet

https://en.wikipedia.org/wiki/Endocannabinoid_system

National Center for Biotechnology Information. PubChem Compound Database; CID=644019,     https://pubchem.ncbi.nlm.nih.gov/compound/644019 (accessed May 8, 2018).

https://doi.org/10.1073/pnas.160105897

5. “The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis” A. M. Malfait, R. Gallily, P. F. Sumariwalla, A. S. Malik, E. Andreakos, R. Mechoulam and M. Feldmann. PNAS August 15, 2000. 97 (17) 95619566;  https://doi.org/10.1073/pnas.160105897 6. https://en.wikipedia.org/wiki/Cannabidiol 7. https://en.wikipedia.org/wiki/TRPV1 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763649/ 9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604182/ 10. https://www.ncbi.nlm.nih.gov/pubmed/17245363 11. Cellular/Molecular Cannabidiol Targets Mitochondria to Regulate Intracellular Ca2 Levels Duncan Ryan, Alison J. Drysdale, Carlos Lafourcade, Roger G. Pertwee, and Bettina Platt School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom. Image found at: https://en.wikipedia.org/wiki/Ligand_(biochemistry)

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