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ABSTRACT
The endocannabinoid system (ECS) is an extensive endogenous signaling system with multiple elements, the number of which may be increasing as scientists continue to elucidate its role in human health and disease. The ECS is seemingly ubiquitous in animal species and is modulated by diet, sleep, exercise, stress, and a multitude of other factors, including exposure to phytocannabinoids, like Cannabidiol (CBD). Modulating the activity of this system may offer tremendous therapeutic promise for a diverse scope of diseases, ranging from mental health disorders, neurological and movement disorders, pain, autoimmune disease, spinal cord injury, cancer, cardiometabolic disease, stroke, TBI, osteoporosis, and others. (Altern Ther Health Med. 2019;25(S2):6-14.)
As interest in, and use of, phytocannabinoids from Cannabis Sativa L (Cannabis) has increased with the number of state-regulated Cannabis programs, heightened scientific attention has been directed toward the mechanisms by which delta-9-tetrahydrocannabiniol (delta-9-THC), cannabidiol (CBD), and other phytocannabinoids exert their physiological effects in the body. These exogenous, plant-derived ligands interact with endogenously produced proteins, receptors, enzymes, and endogenous ligands, in one of the most evolutionarily preserved biological systems known to the life sciences, the endogenous cannabinoid signaling system or endocannabinoid system (ECS).
The ECS is thought to be 600-million-years-old. Present in every animal species, except insects, it evolved as a stress/ harm regulation network that functions to restore homeostasis following cellular stressors.1 The ECS is upregulated and downregulated on a continuous basis as needed. It communicates with all other systems in the body and has been implicated in multiple regulatory functions in both health and disease, including pain, perception, mood, memory, and reward.2,3 This vital physiological system is modulated by diet, sleep, exercise, stress, and a multitude of other factors, including exposure to phytocannabinoids. According to George Kunos, Scientific Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) at the National Institutes of Health (NIH), "Modulating endocannabinoid system activity may have therapeutic potential in almost all diseases affecting humans."
The discovery of the ECS began with the search for the active ingredient in Cannabis.4 CBD was first isolated from a Cannabis extract in 1940.5 Initially, CBD was deemed an inactive constituent because it failed to mimic the effects of Cannabis extracts in animals and humans.6 As a result, it wasn't characterized structurally until 1963,...