The Endocannabinoid System

High school biology was a great class. The tests might not have been fun but we learned many new facts.

(High school biology was fun)

We learned about genetics; that’s where we learned that humans share 98% of our genetic material with chimpanzees. We also learned about evolution; Charles Darwin’s attempt at answering the question “Where do we come from?’   

In my opinion, the coolest thing I learned in biology class was that the body is made up of systems. Some of these systems are the circulatory system, the nervous system and the breathing system. These systems work interdependently to make sure that the body functions in the right way.  

Recently, I learned about the endocannabinoid system, one of the most overlooked systems in the body. Right now you are probably racking your brain to figure out if your biology teacher mentioned the endocannabinoid system. Odds are they didn’t. 

The endocannabinoid system was discovered pretty recently and scientists are still conducting research on it. Their research has revealed a lot about the ECS, and we are going to dive into the research. Strap in. 

The History of The Endocannabinoid System. 

Before we get into the biology of the endocannabinoid system, we need a little history lesson. 

During the late 20th century, scientists conducted lots of research to discover how the various hemp compounds interacted with the brain. However, their research was hampered by the legal status of cannabis. 

In 1988, researchers at the St. Louis University School of Medicine made a major breakthrough in their search. The researchers, William Devane and Allyn Howlett, had discovered that the brains of mammals contains receptors that responded to hemp compounds. It was discovered that these receptors, later named cannabinoid receptors, were the most common neurotransmitter receptors in the brain. 

In 1990, Lisa Matsuda and her team mapped the DNA sequence that encodes a cannabinoid receptor in the brain. This research opened the door for further research in mice that lacked the G-coupled protein receptor. When these mice were given THC, there was no effect. This conclusively proved that for THC to work it had to activate the cannabinoid receptors in the brain. 

Around the same time, a second cannabinoid receptor was discovered, CB2. These receptors were present in the peripheral nervous system and the immune system. This was a major discovery as it led to the discovery of endocannabinoids, a naturally occurring neurotransmitter. 

In 1992, a team led by Dr. Lumir Hanus and Dr. William Devane, discovered the endocannabinoid anandamide. This team would later discover even more endocannabinoids such as homo-gamma-lineleoul ethanolamide and 2-arachidonoylglycerol. 

With these discoveries, scientists worked backwards and traced the metabolic path that THC took in the body. This led to the discovery of the Endocannabinoid System. A previously unknown molecular signaling system that is present not only in humans but also most other biological lifeforms. 

A Pretty Big Deal

The discovery of the endocannabinoid system created a major buzz in the scientific community. It showed scientists that we were a long way off from truly understanding the secrets of the human body. 

More avenues of research were opened up and more researchers are looking into the ECS. Some of the researchers believe that there might be a third cannabinoid receptor in the body and they are working tirelessly to prove it.  They are also working to identify the exact role that the ECS plays in the body. 

How Does The Endocannabinoid System Work?

To understand how the endocannabinoid system works, we need to look at the individual components that make up the system. 

  • Enzymes
  • Endocannabinoids
  • Endocannabinoid receptors 

Endocannabinoids

Endocannabinoid is a portmanteau made by combining the terms endogenous and cannabinoid. In biology the term endogenous refers to something that originates from inside an organism. So in this case endocannabinoids are molecules produced by the body that are similar to naturally occurring cannabinoids. 

In our "history lesson" we referenced the work of a team led by Dr. Lumir Hanus and Dr. William Devane. This team discovered the two most well-known endocannabinoids 

  • Anandamide
(Skeletal formula of anandamide)
2-arachidonoylglycerol

(Skeletal formula of 2-arachidonoylglycerol) 

These endocannabinoids are important in keeping internal functions of the body running smoothly. At the moment, scientists haven’t determined the typical levels of these endocannabinoids. This is because the body only produces them as needed. 

Endocannabinoid Receptors

In the body, receptors are either molecules or regions of tissue that respond to a particular trigger. Some of these triggers can be neurotransmitters, antigens, or hormones. 

Endocannabinoid receptors are tissues that respond to endocannabinoids. There are two main endocannabinoid receptors:

  • CB1- they are widespread in the central nervous system
  • CB2- they are widespread in the peripheral nervous system particularly the immune cells. 

Enzymes

Enzymes are some of the most well-known biological molecules. They are typically proteins and perform a wide range of functions with the most famous being speeding up the rate of metabolic reactions. 

In the endocannabinoid system, enzymes break down endocannabinoids once they have performed their functions. 

The most important enzymes in the endocannabinoid system are:

  • monoacylglycerol acid lipase- this is responsible for the breakdown of 2-arachidonoylglycerol
  • fatty acid amide hydrolase- this is responsible for the breakdown of anandamide

So What Happens?

Endocannabinoids can bind to either the CB1 or CB2 receptor. The binding can result in different outcomes depending on the location of the receptor and type of endocannabinoid. 

An endocannabinoid might bind to a CB1 receptor in a spinal nerve to reduce pain. In another instance an endocannabinoid might bind to a CB2 receptor in an immune cell. This binding would signal to the immune cell that the body is experiencing inflammation. 

The Roles of The Endocannabinoid System

Scientists are still looking into the endocannabinoid system and are yet to determine its exact functions. However, research has linked the endocannabinoid system to various functions such as:

  • Metabolism
  • Sleep
  • Motor Control
  • Stress
  • Liver, Nerve and Skin Function
  • Muscle Formation
  • Stress
  • Mood

CBD and The Endocannabinoid System

At the moment, researchers still aren’t sure how CBD interacts with the endocannabinoid system. What they do know is that it doesn’t bind to the cannabinoid receptors in the same way as THC. 

Scientists do have some ideas on how CBD interacts with the endocannabinoid system. One of the most common hypotheses suggests that CBD binds to an undiscovered third receptor. The other hypothesis states that CBD prevents enzymes from breaking down endocannabinoids. This ensures that the effects of the endocannabinoids can last longer. 

Clinical Endocannabinoid Deficiency 

Clinical endocannabinoid deficiency is one of the most popular theories among researchers. According to this theory, low endocannabinoid levels or a dysfunction in the ECS may contribute to the development of some conditions. 

Some of the conditions that might be caused by CED include migraines, irritable bowel syndrome and fibromyalgia. These conditions have a lot of things in general such as:

  • They don’t have a clear underlying cause
  • Most times they are resistant to treatment
  • They often affect a person concurrently 

If this theory is proved true, then it could provide new insights into treating these conditions. 

Final Thoughts

Although we don't know everything about the endocannabinoid system, we do know that it is vital to the optimal functioning of the body. Lots of brilliant minds are researching the endocannabinoid system, and it’s just a matter of time before we discover all its secrets.