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The Endocannabinoid System

May 4, 2020

Endocannabinoid System

Humans have used cannabis for centuries, but only in the last 50 years or so has any scientific understanding emerged as to how cannabis works within the human body. While the discovery of the first plant cannabinoids took place in the 1940s, it was not until 1946 that THC produced by the cannabis plant was first characterized and synthesized by Gaoni and Mechoulam in Israel.

The discovery of THC in 1964 sparked the search for its mechanism of action. Initially, it was postulated that THC and other cannabinoids increased cell membrane permeability. Eventually, the permeability hypothesis was disproved, however, which led to the search for a protein receptor molecule in the body with which THC might be interacting. The first cannabinoid (CB) receptors in the body were not found until the late 1980s. These receptors turned out to comprise a new series of homeostatic regulatory mechanisms within the body, which was named the endocannabinoid system.

The endocannabinoid system is a very complex regulatory system, broad in its function, and found within all complex animals, from fish to humans. It regulates such diverse functions as memory, digestion, motor function, immune response and inflammation, appetite, pain, blood pressure, bone growth, and the protection of neural tissues, among others. The endocannabinoid system comprises three principal elements: endocannabinoid receptors; specialized molecules called endocannabinoids that interact with those receptors; and enzymes that either synthesize or metabolize the endocannabinoids.

The two primary subtypes of classical cannabinoid receptors in the endocannabinoid system are CB₁ and CB₂. These receptors are distributed throughout the central nervous and immune systems, and within many other tissues, including the brain, gastrointestinal system, reproductive and urinary tracts, spleen, endocrine system, heart, and circulatory system. Many of the physiological effects of cannabis were first believed to be caused by the interaction of phytocannabinoids with the CB₁ and CB₂ receptors. In fact, because the THC family of cannabinoids are the only compounds that robustly activate the CB₁ receptor, some have even suggested that its name be changed from CB₁ to the THC receptor.

It is now known that cannabinoid interactions extend beyond the CB₁ and CB₂ receptors, however, and interact with other CB-type and related receptors and ion channels. These include the so-called orphan CB receptors GPR55, GPR18, and GPR119; the transient receptor potential vanilloid-type channel (TRPV1, associated with pain transmission and typically activated by temperatures over 109℉/43℃, hot peppers or horseradish, and also known as the capsaicin receptor); and the peroxisome proliferator-activated nuclear receptors (PPAR-alpha and -gamma regulate important metabolic functions involving fatty acid storage, glucose metabolism, and development and progression of malignancies). Of these, other CB-type receptors, the orphan or candidate cannabinoid receptors are becoming increasingly important to the understanding of the endocannabinoid system.

The following information is presented for educational purposes only. Summit Releaf distributes this information to provide an understanding of the potential benefits of medical marijuana for patients living with one of the approved Ohio Medical Marijuana Control Program qualifying conditions for an Ohio marijuana card. Links to third party websites do not constitute an endorsement of these organizations by Summit Releaf and none should be inferred.

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