The term “Endocannabinoids” describes a class of compounds that function as hormones or neurotransmitters in the body’s Endocannabinoid System (ECS). The endocannabinoid system refers to a system where parts of the body have proteins that bind endocannabinoids. The proteins, called receptors, bind, and react to endocannabinoids. These receptors are embedded in the cell membranes. Endocannabinoids that become bound to the receptors cause a change in cell membrane polarity. This membrane depolarization activates the cell in a variety of ways. Research has found these receptors throughout the body, and they appear to involve very significant functions.
Research has identified two main cannabinoid receptors: CB1R and CB2R. CB1R receptors are found predominantly in the brain and nervous system, but also in peripheral organs and tissues. CB2R are found throughout the body, but especially on white blood cells.
Experiments have found that the endocannabinoids regulate both physiological and cognitive processes. Other effects include immunity, cancer surveillance, pain, mood, memory, fertility, and pregnancy. The ECS affects ‘homeostasis’, those processes that moderate feedback that maintains stability and biochemical equilibrium.
Cannabis and hemp contain cannabidiol (CBD), which is a phytocannabinoid like THC. CBD acts as a rather weak antagonist at both CBRs. However, it is bound and reacts with other receptors (TRPV1, TRPM8, and CB1).
In 1992, Raphael Mechoulam discovered the first endocannabinoid, Anandamide (ANA)(and also known as N-arachidonoylethanolamine or AEA). Anandamide and all the other endocannabinoids have long chains of carbon atoms and are made from fatty acid. The CB1 receptor (sometimes CB1R) binds and is stimulated by anandamide (AEA) and THC (Tetrahydrocannabinol, the psychoactive component in cannabis). When a drug stimulates a receptor, it is said to be an agonist, so THC and AEA are agonists of CB1R. Research has found Anandamide in nearly all tissues The name 'anandamide' is taken from the Sanskrit word ananda, which means "joy, bliss, or delight".
Dr. Mechoulam also helped discover 2-Arachidonoylglycerol. 2-AG acts to stimulate CB1R receptors, but 2-AG is thought to be the primary agonist (stimulator) of the CB2R receptor. When a molecule stops the receptor protein from being activated, it is called an antagonist.
Virodhamine (O-arachidonoyl ethanolamine; O-AEA) acts as an antagonist of the CB1 receptor and is an agonist of the CB2 receptor. Research has shown that Virodhamine will lower body temperature in mice.
Oleoylethanolamide (OEA) has been found to increase the levels of peroxisome, a type of cell organelle. Cells can have peroxisomes attached to their cell membrane. Peroxisomes generate hydrogen peroxide from oxygen, and this is used to break down fatty acids, a process called lipolysis. OEA stimulates a receptor alpha (PPAR-α) to increase lipolysis.
2-Oleoylglycerol is bound by the receptor GPR119, and activation signals the release of GLP-1. GLP-1 stands for Glucagon-like peptide #1. GLP-1 is a 30- or 31-amino-acid-long peptide hormone secreted by intestinal L-cells. GLP-1 is an incretin, and thus, GLP-1 can decrease blood sugar levels by increasing the secretion of insulin.
Palmitoyl Ethanolamide (PEA) also affects peroxisomes. Research indicates that PEA is bound by peroxisome proliferator-activated receptor alpha (PPAR-α). PEA also is bound by G-coupled receptors GPR55 and GPR119. Some researchers don’t classify PEA as an endocannabinoid, but PEA’s structure and action are similar enough to be included here. Some research suggests that PEA binds to a receptor on the surface of cell nuclei, inside the cells. Research has found PEA has effects that include reducing pain and chronic inflammation. Other reports indicate PEA can provide neuroprotection and reduce convulsions. Research into PEA has increased as it has been found to provide pain relief without significant adverse effects, and has also been useful for relieving pain in various skin conditions.
The endocannabinoids have relatively small differences in form, yet these small differences are critical to being bound by various receptors. In the top row, the presence of double bonds may curl the chain into a helix. Those in the bottom row may not be curled and may assume a different three-dimensional shape.
How do cannabinoids (THC, CBD, etc.) mimic these endocannabinoids, given that their structures are so different? The best guess is that the when the endocannabinoids are curled up, their 3D electronic structure IS similar to the cannabinoids. Cannabinoids impersonate the endocannabinoids, but being different molecules, they have a completely different rates and methods of being degraded by the body.
Despite their seeming similarity, endocannabinoids have extremely different and very specific functions. We observe that many of these functions are critical for health and well-being. Scientists speculate that various disease states may result if people develop difficulties making or binding these molecules. That condition is described by the term: “endocannabinoid deficiency.” It may be that such difficulties develop with age, and that people can use cannabinoids to compensate. Thus, some advocates suggest that people over 50 begin to take CBD supplements. Anti-drug policies prevent researchers from doing clinical trials (on drugs that millions of people are taking). Fortunately, cannabinoids almost never cause an adverse reaction. ///
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