Cannabinoids & the Endocannabinoid System

Homeostasis is the concept that most biological systems are actively regulated to maintain conditions within a narrow range. Our body doesn’t want its temperature to be too hot or too cold, blood sugar levels too high or too low, and so on. Conditions need to be just right for our cells to maintain optimum performance, and exquisite mechanisms have evolved to draw them back to the optimum zone if they move out. The body’s endocannabinoid system (ECS) is a vital molecular system for helping maintain homeostasis—it helps cells stay in their optimum zone.

Because of its crucial role in homeostasis, the ECS is widespread throughout the animal kingdom. Its key pieces evolved a long time ago, and the ECS can be found in all vertebrate species.  The three key components of the ECS are Cannabinoid receptors found on the surface of cells, Endocannabinoids, small molecules that activate cannabinoid receptors and Metabolic enzymes that break down endocannabinoids after they are used.

Cannabinoid receptors sit on the surface of cells and “listen” to conditions outside the cell. They transmit information about changing conditions to the inside of the cell, kick-starting the appropriate cellular response.  There are two major cannabinoid receptors: CB1 and CB2. These aren’t the only cannabinoid receptors, but they were the first ones discovered and remain the best-studied. CB1 receptors are one of the most abundant receptor types in the brain. These are the receptors that interact with THC to get people high. CB2 receptors are more abundant outside of the nervous system, in places like the immune system. However, both receptors can be found throughout the body.

Endocannabinoids are molecules that, like the plant cannabinoid THC, bind to and activate cannabinoid receptors. However, unlike THC, endocannabinoids are produced naturally by cells in the human body (“endo” means “within,” as in within the body).
There are two major endocannabinoids: anandamide and 2-AG. These endocannabinoids are made from fat-like molecules within cell membranes, and are synthesized on-demand. This means that they get made and used exactly when they’re needed, rather than packaged and stored for later use like many other biological molecules.

The third piece of the endocannabinoid triad includes the metabolic enzymes that quickly destroy endocannabinoids once they are used. The two big enzymes are FAAH, which breaks down anandamide, and MAGL, which breaks down 2-AG. These enzymes ensure that endocannabinoids get used when they’re needed, but not for longer than necessary. This distinguishes endocannabinoids from many other molecular signals in the body, such as hormones or classical neurotransmitters, which can persist for many seconds or minutes, or get packaged and stored for later use.

The three key components of the ECS can be found within almost every major system of the body. When something brings a cell out of its optimum zone, these three pillars of the ECS are often called upon to bring things back, thus maintaining homeostasis. Because of its role in helping bring things back to their physiological optimum zone, the ECS is often engaged only when and where it’s needed. Dr. Vincenzo Di Marzo, Research Director at the Institute of Biomolecular Chemistry in Italy, put it to us this way:

“With the ‘pro-homeostatic action of the ECS’ we mean that this system of chemical signals gets temporarily activated following deviations from cellular homeostasis. When such deviations are non-physiological, the temporarily activated ECS attempts, in a space- and time-selective manner, to restore the previous physiological situation (homeostasis).” In other words, the ECS helps bring things back to the biologically optimum zone.

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