The Endocannabinoid System

The Endocannabinoid System and Endogenous Cannabinoids

The endocannabinoid system (ECS) is a widespread neuromodulatory system that plays an important role in central nervous system development, synaptic plasticity, and the response to endogenous and environmental insults. 


The ECS is comprised of cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes responsible for the synthesis and degradation of the endocannabinoids.


The ECS plays role in regulating a range of key functions and processes, including; appetite and digestion, metabolism, chronic pain, immune system responses, mood, learning and memory, motor control, sleep, cardiovascular system function, muscle formation, bone remodelling and growth, liver function, reproductive system function and skin and nerve function.

These functions all contribute to homeostasis, which refers to the stability of your internal environment. For example, if an outside force, such as pain from an injury or a fever, throws off your body’s homeostasis, your ECS kicks in to help your body return to its ideal operation. Homeostasis may be the primary role of the ECS.


Endocannabinoid receptors


The most abundant cannabinoid receptor is the CB1 cannabinoid receptors, however CB2 cannabinoid receptors, transient receptor potential (TRP) channels, and peroxisome proliferator-activated receptors (PPAR’s) are also engaged by some cannabinoids.


These receptors are found throughout the human body. Endocannabinoids bind to the receptors to signal to the ECS when it needs to take action. CB1 receptors are mostly found in the central nervous system while CB2 receptors are mostly found in your peripheral nervous system, especially immune cells. 


Endocannabinoids also work with other receptors in the ECS such as the PPAR-alpha receptor, the TRPV receptor and the GPR55 - the receptors are most important for Palmitoylethanolamide, a fatty amine closely related to anandamide.




Enzymes are responsible for breaking down endocannabinoids once they’ve carried out their function. There are two main enzymes responsible for this; fatty acid amide hydrolase, and monoacylglycerol acid lipase. Fatty acid amide hydrolase breaks down AEA. Monoacylglycerol acid lipase typically breaks down 2-AG.


Endogenous cannabinoids (Endocannabinoids)


Endocannabinoids, also called endogenous cannabinoids, are molecules made by your body. They’re similar to cannabinoids, but they’re produced by your body. 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide) are the best-studied endogenous cannabinoids.

Exogenous cannabinoids, such as tetrahydrocannabinol, produce biological effects through their interactions with cannabinoid receptors. Endocannabinoids can bind to either receptor. The effects that result depend on where the receptor is located and which endocannabinoid it binds to.

For example, endocannabinoids might target CB1 receptors in a spinal nerve to relieve pain. Others might bind to a CB2 receptor in your immune cells to signal that your body’s experiencing inflammation, a common sign of autoimmune disorders.


2-Arachidonoyl Glycerol


| C23H38O4 |


2-arachidonoylglycerol is an endocannabinoid and an endogenous agonist of the cannabinoid receptors (CB1 and CB2). It is an ester formed from omega-6-arachidonic acid and glycerol. It has a role as a human metabolite. It is an endocannabinoid and a 2-acylglycerol 20:4. It derives from an arachidonic acid.


Arachidonoyl Ethanolamide (Anandamide)


| C22H37NO2 |

Anandamide, also known as N-arachidonoylethanolamine is an N-(polyunsaturated fatty acyl) ethanolamine resulting from the formal condensation of carboxy group of arachidonic acid with amino group of ethanolamine.

It has a role as a neurotransmitter, a vasodilator agent and a human blood serum metabolite.

It is a N-(long-chain-acyl) ethanolamine, an endocannabinoid, a N-(polyunsaturated fatty acyl)ethanolamine and a N-acylethanolamine 20:4. It derives from an arachidonic acid.

Despite similarities in chemical structure, 2-AG and anandamide are synthesized and degraded by distinct enzymatic pathways, which impart fundamentally different physiological and pathophysiological roles to these two endocannabinoids.



Image: [ 2-arachidonoyl glycerol ]


Image: [ arachidonoyl ethanolamide; (anandamide) ]