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How Cannabinoids Interact with Their ECS Receptors

How Cannabinoids Interact with Their ECS Receptors - SOL✿CBD

Even a quick search of the National Center for Biotechnology Information for the term cannabinoids returns over 15,000 published articles on the subject. These articles span the gauntlet of scientific and medical inquiry, and there are new additions on an almost daily basis. However, even with this immense body of research there are still many questions unanswered about cannabinoids, particularly the intricate ways in which they stimulate and influence the activity of the endocannabinoid system (ECS). In fact, there is still discussion on exactly how many types of endocannabinoid receptors there are in the human body, and even more discussion on how certain cannabinoids manage to activate them.

With these questions in mind, it might be time for a quick review of exactly what we currently understand to be going on within the world of cannabinoids and the endocannabinoid system. After all, considering the essential nature of this system, and the serious nature of the health issues that can happen if it is imbalanced, we all should have at least a basic understanding of how cannabinoids interact with our ECS receptors.

The Endocannabinoid System

First and foremost, what is the endocannabinoid system? It is essentially a regulatory network of receptors spread throughout the bodies of all mammals. While each of the receptors operate differently depending on where they are located in the human body, they are all essentially trying to maintain homeostasis. This means, they are all working towards maintaining a constantly consistent internal environment in response to different external and internal stressors. When they are functioning properly, they foster the perfect environment for the existence of life down to the most basic cellular level.

Endocannabinoid receptors are found throughout the body, but are most highly concentrated in the brain, organs, central nervous system and the immune system. They operate as a communications network between different kinds of cells, and when triggered by different stimuli, they will in turn trigger a subsequent reaction - aiming as always to create a balanced internal environment.

Interestingly enough, the endocannabinoid system was only discovered due to research into cannabinoids found within cannabis, and not the other way around. This was because researchers postulated that just as there are receptors capable of interacting with opioids, there must be some sort of receptor responsible for interacting with cannabis derived cannabinoids. Thus, in 1990, after decades of study, scientists discovered the endocannabinoid system thanks in part to their research into cannabis.

Cannabinoid Receptors

There are currently understood to be two primary cannabinoid receptors, but the debate continues on other potential receptors that may also be influenced by cannabinoid stimulation. The first cannabinoid receptor discovered was the CB1 receptor. This receptor is primarily concentrated throughout the mammalian brain, but also in lesser concentrations found in other tissues and cells like within the glands, organs and central nervous system. The secondary receptor, and perhaps the least understood one, is the CB2 receptor, which is found primarily within the immune system and the associated tissues.

Cannabinoid receptors evolved over 600 million years ago, and while the human endocannabinoid system does respond equally to plant produced cannabinoids (ie. Cannabis derived), we also naturally produce endocannabinoids. The two primary endocannabinoids known to be naturally produced by the human body are anandamide and 2-arachidonoylglycerol (2-AG). Anandamide’s main focus is to activate CB1 receptor, however it does have a lower tendency towards the CB2 receptor. The other endocannabinoid, 2-AG, interacts with the CB2 receptors.

In a functional, well-balanced system, both levels of these endocannabinoids would be available in perfect quantities to achieve homeostasis, however our bodies are constantly working to counteract both internal and external stressors, meaning it is constantly working to produce or reduce these quantities. A perfect balance is rarely achieved. This is where phytocannabinoids (or plant based cannabinoids) come in. They are able to interact with the endocannabinoid system equally as well as our own versions.

Cannabinoids from Cannabis

The cannabis plant has over 60 known cannabinoids, and each of these have a unique method of activating the human endocannabinoid system. At the moment, only a few such as THC and CBD are well understood, and the research is ongoing into how many of the others function. At the moment are a few different ways in which phytocannabinoids are known to influence our endocannabinoid system.

  • Key and Lock: One of the most fully understood methods by which cannabinoids trigger endocannabinoid receptor activity, is through direct interaction. This is best understood by imagining the receptor as a lock, and the cannabinoid as a key. The cannabinoid fits perfectly into the lock, and through this mechanism, effectively opens a door. This has been found to be the relationship between the CB1 receptors in the brain and THC cannabinoids.
  • Indirect Activation: Less understood, is the method of indirect activation where cannabinoids do not lock into receptors, but still manage to elicit a response from the receptor. One of the best known examples is the way that CBD indirectly stimulates the CB1 receptor as it is locked onto a THC molecule. It essentially manages to decrease the duration and strength of the THC’s relationship with the CB1 receptor, without actually binding to it itself.
  • 3rd Party Activation: This is one of the newest areas of research, and the least understood. It can mean that instead of working with the CB1 or the CB2 receptor, the cannabinoid instead interacts with another receptor like dopamine or serotonin. Some cannabinoids also focus on influencing the character of other cannabinoids. For example, changing it from CBD to CBG once consumed. At the moment scientists believe that CBD specifically carries some of these 3rd party traits.



Blesching, Uwe. The Cannabis Health Index. North Atlantic Books, 2015. Print.

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