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Endocannabinoid System (ECS)
Our endocannabinoid system is a body system that was discovered in 1992, at the Hebrew University in Jerusalem, Dr. Lumir Hanus along with American researcher Dr. William Devane when they isolated the first known endocannabinoid anandamide. This system plays a pivotal role in our overall health and well-being. Due to the 2018 Farm Bill scientists are now exploring this system and all of its implications.
Cannabidiol (CBD) is a pleiotropic drug in that it produces many effects through a multitude of pathways. Scientific literature has identified more than 60 molecular targets of CBD.
CBD does not have a binding affinity for the two cannabinoid receptors (CB1 and CB2). Cannabidiol modulates non-cannabinoid receptors and ion channels. CBD also acts through receptor-independent pathways. CBD delays the “reuptake” of endogenous cannabinoids like anandamide. CBD also increases or decreases the binding action of certain G-protein coupled receptors.
Here are some of the ways that CBD exhibits its therapeutic effects.
CBD directly interacts with various ion channels to bestow therapeutic effects. CBD binds to TRPV1 receptors, which also function as ion vanilloid cannabinoid receptors.
TRPV (transient receptor potential cation channel subfamily V) TRPV1 receptor variants or subfamilies that mediate the effects of a wide range of medicinal herbs.
TRPV1 aka “vanilloid receptor,” named after the vanilla bean. Vanilla contains eugenol, an essential oil that has antiseptic and analgesic properties; it also helps to clean blood vessels. Historically, the vanilla bean has been used as a natural cure for headaches.
CBD binds to TRPV1, which may influence pain perception.
Capsaicin—the pungent compound in hot chili peppers—activates TRPV1. Anandamide, the endogenous cannabinoid, is also a TRPV1 agonist.
Studies indicate that CBD functions as an antagonist that blocks, or deactivates, another G protein-coupled receptor known as GPR55. It is involved in modulating blood pressure and bone density, among other processes.
GPR55 promotes osteoclast cell function, which facilitates bone reabsorption. Hyperactive GPR55 receptor signaling is associated with osteoporosis.
GPR55, when activated, also promotes cancer cell proliferation, according to a 2010 study by researchers at the Chinese Academy of Sciences in Shanghai. This receptor is expressed in various types of cancer.
CBD is a GPR55 antagonist, as University of Aberdeen scientist Ruth Ross disclosed at the 2010 conference of the International Cannabinoid Research Society in Lund, Sweden. By blocking GPR55 signaling, CBD may decrease both bone reabsorption and cancer cell proliferation.
Researchers at the University of San Paulo in Brazil and King’s College in London have looked into CBD. CBD directly activates the serotonin receptor 5-HT1A (hydroxytryptamine), thereby creating an anti-anxiety effect. This protein receptor has a myriad of biological and neurological processes, including anxiety, addiction, appetite, sleep, pain perception, nausea, vomiting, and more.
CBD ALLOSTERIC MODULATOR
CBD also functions as an allosteric receptor modulator, which means that it can change the function of how a receptor transmits a signal by changing the shape of the receptor.
Australian scientists report that CBD acts as a “positive allosteric modulator” of the GABA-A receptor. Gamma-Aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the central nervous system. The sedating effects of Xanax and other benzodiazepines due to GABA receptor transmission. CBD may reduce anxiety by changing the shape of the GABA-A receptor in a way that amplifies the natural calming effect of GABA.
CBD also may have an anti-cancer effect by activating peroxisome proliferator activated receptors (PPARs). Activation of the receptor known as PPAR-gamma has an anti-proliferative effect as well as an ability to induce tumor regression in human lung cancer cell lines. PPAR-gamma activation degrades amyloid-beta plaque, a key molecule linked to the development of Alzheimer’s disease. This is one of the reasons why cannabidiol, a PPAR-gamma agonist, may be a useful remedy for Alzheimer’s patients.
PPAR receptors also regulate genes that are involved in energy homeostasis, lipid uptake, insulin sensitivity, and other metabolic functions. Diabetics may benefit from a CBD-rich treatment regimen because of this.
According to a team of Stony Brook University scientists, CBD functions as an anandamide reuptake and breakdown inhibitor, thereby raising natural levels in the brain. Enhancing endocannabinod tone via reuptake inhibition may be a key mechanism whereby CBD bestows neuroprotective effects against seizures, as well as many other health benefits.
CBD’s anti-inflammatory and anti-anxiety effects are in part attributable to its inhibition of adenosine reuptake. A1A and A2A adenosine receptors play significant roles in cardiovascular function, regulating caradiac oxygen consumption and blood flow. These receptors have anti-inflammatory effects.