Cannabinoid Receptors: An In-Depth Look


I have been writing about cannabinoid receptors for years and yet often felt I hadn’t completely grasped how they fit into the inner workings of our endocannabinoid system (ECS). What are cannabinoid receptors? Are we programmed via receptors to accept and process cannabis in our bodies? How does this complicated mechanism work? Answering those questions is my goal for this article.

You can’t mention cannabinoid receptors without referencing the endocannabinoid system. Simply put, the ECS is a very large neurotransmitter network and its goal is to achieve homeostasis or balance; a stable internal environment despite changes in one’s external environment. When our ECS is out of balance, the human body experiences a myriad of diseases and symptoms. The ECS is composed of messengers and receivers. Endocannabinoid molecules like anandamide and 2-arachidonoylglycerol (2-AG) are produced by the brain and can be found in organs, connective tissue, glands and immune cells.

The effects of anandamide, the body’s natural THC, lasts for a much shorter time than does that of the THC in cannabis. Cannabinoids search out and activate cannabinoid receptors CB1 and CB2. They regulate many of your bodily functions including the immune system, nervous system, reproductive system, digestive and gastrointestinal systems, as well as controlling your mood. Your ECS is constantly sending messages to all your body functions to make sure that everything is working smoothly. If it encounters a problem, new messages are sent to receptors to recalibrate them, which modifies how you feel and function. There is very little research being done on the ECS and cannabinoid receptors. Much more is needed in order to fully understand all the nuances of their roles.

While it may seem that the creation of cannabinoids in cannabis is to interact with cannabinoid receptors, the primary function of cannabinoid receptors is to receive endocannabinoids and their messages from your brain. If you have a deficiency in your ECS, cannabis stimulates your receptors and supplements your ECS. This is why some cannabis researchers refer to many diseases as Clinical Endocannabinoid Deficiencies.

  • CB1 receptors, mainly located in the brain, nervous system, lungs, liver and kidneys, bind with our natural endocannabinoids and THC to provide relief from pain, nausea, depression, etc.
  • CB2 receptors, mainly located in the immune system and especially in the spleen and gastrointestinal system, bind with the natural endocannabinoid 2-AG and CBD to regulate appetite, relieve inflammation and pain.
  • CBN is thought to be a 3rd type of cannabinoid receptor for which there is little conclusive evidence and for which research is underway and ongoing.

How Do Cannabinoid Receptors Work? 

The most common analogy to explain the mechanism of cannabinoid receptors is that of the lock, (receptors), and the key, (cannabinoids THC and CBD.) Depending on which receptor engages with which cannabinoid will determine which messages will be sent out to your body. For example, CBD oil, which binds with a CB2 receptor, can inhibit appetite while a high-THC strain, which binds more easily with a CB1 receptor, may increase appetite. This explains why some strains give you the munchies while others do not.

It seems the operating system of the ECS is more complicated than just the lock and key analogy. It is a check on avoiding an overload in your system. If that is the case, the ECS regulates the amount of activation by restricting the messages being sent to the body. It can act as a regulator by decreasing how often, how quickly and where the messages are being sent. This is realized by an immune response inhibition, reduction in inflammation, decrease in blood pressure and a relaxation in muscles and nerves.

It is now known that when CBD increases the number of endocannabinoids in your body, it affects the way certain enzymes operate. The fatty acid amide hydrolase enzyme (FAAH) breaks down and removes excess anandamide from your body. CBD stops FAAH from doing its job so that more anandamide is available for consumption by the body.

The Expression of Cannabinoid Receptors 

We already discussed that cannabinoid receptors are located in different parts of the body. They also have different density and amounts which is the definition of the “expression” of the receptors. Each individual has a unique expression based on the balance, number and concentration of their cannabinoid receptors. One’s distinct expression of your cannabinoid receptors provides your distinct experience when consuming a strain of cannabis. This explains why finding the right strain and delivery method is so personal but can also be so challenging. What works for you, probably doesn’t work for your friend with the same disease and symptoms.

The rule of thumb for new cannabis users is start with a low dose and increase it slowly. There will always be trial and error involved. Once new patients understand the importance of the relationship between the cannabinoids in cannabis and the function of cannabinoid receptors and the ECS, they can make more educated choices in their cannabis product selections.

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