The Endocannabinoid System: What is it?

The discovery of marijuana’s psychoactive component tetrahydrocannabinol (THC) opened the way for academic research, and specifically for Czech analytical chemist Lumir Hanus and American pharmacologist William Devane, to the revelation of a whole endogenous signaling system, now known as the endocannabinoid system (ECS). A biological system composed by endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors (CBRs), and cannabinoid receptor proteins that are expressed throughout the vertebrate central nervous system (including the brain) and peripheral nervous system. In other words, it’s a very complex cell-signalling system. 

After years of research since its discovery, it is becoming clear the ECS plays a crucial role in the human body’s inner workings. As such, a better understanding of this system, and of cannabinoids in general, will likely lead to better health outcomes.

Let’s try and break it down. The ECS is known to consist of three core components: receptors, endocannabinoids, and enzymes.

Receptors
Cannabinoid receptors are receptors that can be observed throughout the body, where endocannabinoids may attach to a receptor, causing different results depending on the location of the receptor in the body, signalling that the ECS needs to take action.  Two primary cannabinoid receptors have been identified throughout the body:

• CB1 is mainly in the central nervous system (CNS). CB1 receptors are mainly found in the brain and central nervous system, and to a lesser extent in other tissues.
• CB2 is mainly in the peripheral nervous system (PNS) and in immune cells. CB2 receptors are found in peripheral organs, especially cells associated with the immune system.

For instance, endocannabinoids could target CB1 receptors in a spinal nerve to relieve pain or bind to a CB2 receptor in an immune cell, signalling that the body is experiencing inflammation.

Endocannabinoids
They are similar to the cannabinoids that are present in the cannabis sativa plant, but endocannabinoids are produced naturally in the human body. The term ‘‘endo’’ means “within,” as in within the body. They are essentially chemical messengers in the body that send signals between nerve cells, also known as neurotransmitters.

Research has identified two key endocannabinoids (so far):

• Anandamide (AEA or arachidonoyl ethanolamide)
• 2-archidonoyl glyerol (2-AG)

Enzymes
Enzymes are substances that act as catalysts in living organisms, regulating the rate at which chemical reactions proceed without itself being altered in the process. Enzymes are accountable for breaking down the endocannabinoids after they carry out the needed response.

The two main enzymes that break down endocannabinoids are:

• fatty acid amide hydrolase, which breaks down AEA
• monoacylglycerol acid lipase, which breaks down 2-AG
  
  

Main Functions

• appetite and digestion
• metabolism
• inflammation and other immune system responses
• mood
• chronic pain
• learning and memory
• motor control
• sleep
• cardiovascular system function
• muscle formation
• bone structuring and growth
• liver function
• reproductive system function
• skin and nerve function
• stress 

The academic literature has linked the ECS to the above mentioned functions. These functions all contribute to homeostasis, which is responsible for the stability of the human body's internal environment. For example, when you come down with a fever or an infection, the ECS can help your body maintain its homeostasis. Today, experts believe that maintaining homeostasis is the primary role of the ECS. 

Everything we know on the ECS suggests that it plays a significant role in maintaining balance and proper function in the body. However, more research, perhaps larger clinical trials and studies focused on cannabis and ECS, is needed to make more conclusive suggestions. 

The following sources were used in this blog: 

• Luciano De Petrocellis, Maria Grazia Cascio & Vincenzo Di Marzo. British Journal of Pharmacology (2004) 141, 765–774 The endocannabinoid system: a general view and latest additions
• Shenglong Zou & Ujendra Kumar. Int J Mol Sci. (2018) vol. 3: 833. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/
• Patricia H. Reggio. Curr Med Chem. (2010); 17(14): 1468–1486: Endocannabinoid Binding to the Cannabinoid Receptors: What Is Known and What Remains Unknown
• Healthline
• Medical News Today