Understanding the Endocannabinoid System

Understanding the Endocannabinoid System

Understanding the Endocannabinoid System

Have you heard of the ‘Endocannabinoid System (ECS)?’ After years of research, scientists are now beginning to understand the unique relationship between cannabinoids and our health and wellbeing, and it primarily revolves around a relatively newly known physiological system called the Endocannabinoid System.

Similar to Cannabis, our bodies naturally produce our own cannabinoids, known as endogenous cannabinoids, or ‘Endocannabinoids.’ The Endocannabinoids found within our body are responsible for signaling our cells to perform various metabolic functions. Initially formally described in the late 1990s, the ECS is a cellular receptor network that is spread throughout the human body and helps to regulate vital body functions, such as sleep, appetite, pain, inflammation, memory, mood, and reproduction. [1]

This unique system is comprised of three important components that include endocannabinoids, chemical receptors, and the enzymes responsible for building and breaking down cannabinoid receptors and endocannabinoids. 




Endogenous cannabinoids or endocannabinoids are molecules that have a direct effect on the way that cannabinoid receptors and other chemical receptors function. The two primary endocannabinoids are Anandamide and 2-Arachidonoylglycerol more commonly known as 2-AG. These are the two main stimulators of the CB receptors.  

Research is revealing that there are numerous other endocannabinoids in the body but they are poorly understood currently.




Cellular receptors are a part of the cellular signaling system. These cell receptors are being used to communicate through all of the organs and networks found within the body. These cells receive information from the external environment via structures (proteins) that sit on the surface of the cell membrane called receptors. Receptors receive information from an external source and the interaction with one another changes the cell function.

We have two primary types of Endocannabinoid (CB) receptors, known as CB1 and CB2. There are numerous other chemical receptors that cannabinoids interact with that may one day be considered cannabinoid receptors or components of the endocannabinoid system. For instance, TRPV1 receptors are considered by many to be an additional component of the ECS.[2] Some researchers are now suggesting that Serotonin receptors may also be a component of the ECS.[3] [4] [5]

CB1 receptors are located primarily in the brain and central nervous system cells, as well as in some peripheral tissues.[6] CB1 receptors are responsible for the intoxicating effects of THC, as well as short-term memory loss, allowing one to ‘forget’ the experience of pain or trauma.[7] CB1 receptors can regulate nervous system function and pain response by modulating the relationship between two specific neurotransmitters, glutamate and GABA.[8]



CB2 is closely associated with the immune system, playing a vital role in two essential processes with potentially profound implications for wellness: autophagy and apoptosis.[9] These terms refer to the cleaning of cellular debris and the programmed death of unneeded or malfunctioning cells in our bodies.


Now, here is the tricky part: Unlike THC, CBD does not bind very well to the body’s cannabinoid receptors. It doesn’t bind to CB1 receptors at all, and very little to CB2.[10] However, it may indirectly stimulate CB1 and CB2 receptors by stimulating the production of the body’s own endocannabinoids, such as anandamide. Additionally, CBD inhibits an enzyme that would typically break anandamide down.[11] This causes anandamide to linger longer in the body, allowing it to stimulate cannabinoid receptors more than it might otherwise.

CBD’s direct effects are more likely attributed to its activity at other chemical receptors in the body, including adenosine, serotonin, vanilloid, and ppar-gamma receptors, to name a few.[12]


Beyond CB1 and CB2 receptors, there are numerous other chemical receptors in the body that researchers suggest should be considered part of the endocannabinoid system. These include receptors like GPR55, GPR18, GPR35, TRPV1, 5-HT2A, and PPAR-gamma. However, more research is needed in order to understand exactly how all of these other chemical receptor types fit into the picture.



The final piece to the ECS puzzle is the enzymes responsible for manufacturing endocannabinoids or breaking down the endocannabinoids in the body to prepare them for excretion. Our body has to manufacture cannabinoids when it needs them and relies on enzymes to do it. When the body needs to send messages to cells to change functions it needs to produce enzymes before it can produce endocannabinoids, because, unlike many other signaling compounds in the body, the body does not store excess endocannabinoids - it produces them on demand.[13]  The body also uses enzymes to stop cannabinoids from signaling by breaking them down and removing them from the cell.


There are numerous ways to modulate the ECS without consuming cannabinoids like CBD or THC. Some of the best ways to modulate the ECS include aerobic exercise and proper gut health.[14] Additional activities that may influence the ECS include yoga, massage, and even meditation.


To learn more about the ECS, check out this video of Chief Formula Officer, Dr. Jason Miller.


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12 https://www.projectcbd.org/science/how-does-cbd-work

13 Basavarajappa BS. Neuropharmacology of the Endocannabinoid Signaling System-Molecular Mechanisms, 13 Biological Actions and Synaptic Plasticity. Curr Neuropharmacol. 2007. 5(2): 81-97.

14 McPartland JM et al. Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system. PLoS ONE. 2014. 9(3): e89566.