The Endocannabinoid System

What is Cannabis and CBD?

Cannabis sativa has been used historically as medicine, dating back 1000 years BC in India and at least 5000 years in China.  Hemp and cannabis are both members of this plant species.

Varieties of cannabis can contain THC concentrations that range from 10% to up to 30%. This is what gives its psychoactive effect.  Cannabis is naturally lower in Cannabidiol (CBD) than THC, and CBD is completely non-psychoactive.  Legislative levels of THC require a level of 0.2% in CBD products, and thus it is safe for use.

What is the Endocannabinoid system (ECS)?

To understand the human endocannabinoid system, it’s helpful to know a little about one of the most fundamental concepts in biology: homeostasis.

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 balance. The body’s endocannabinoid system (ECS) one system for helping maintain homeostasis.

Components of the endocannabinoid system (ECS)

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:

  1. Cannabinoid receptors found on the surface of cells
  2. Endocannabinoids, small molecules that activate cannabinoid receptors
  3. Metabolic enzymes that break down endocannabinoids after they are used

We will very briefly look at the first 2.

Cannabinoid receptors

Cannabinoid receptors sit on the surface of cells and respond to conditions outside the cell. Changing conditions are communicated 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. 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

Endocannabinoids are molecules that, like the plant cannabinoid, bind to and activate cannabinoid receptors. However, 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 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 normal balance, these pillars of the ECS are often called upon to bring things back, thus maintaining homeostasis. 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).”

How do plant cannabinoids like CBD interact with the endocannabinoid system?

The reason that plant cannabinoids have psychoactive and medicinal effects within the body is, in large part, because we have an endocannabinoid system (ECS) that they can interact with.

References

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Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333-49. [PDF]

Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153(2):199-215. [PDF]

Wilson RI, Nicoll RA. Endocannabinoid signaling in the brain. Science. 2002;296(5568):678-82. [PDF]

Zlebnik NE, Cheer JF. Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation? Annu Rev Neurosci. 2016;39:1-17. [PDF]

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