The Endocannabinoid System: An Introductory Review

What is the endocannabinoid system (ECS)?
As cannabis research advances, we are learning new things about the plant and how it interacts with our bodies all the time. One major discovery came quite recently in 1990, when researchers at the National Academy of Science’s Institute of Medicine identified the DNA sequence for a THC-sensitive receptor in a rat’s brain. This followed research conducted by Dr. Allyn Howlett in the 1980s, who first hypothesized that cannabinoids might bind to a specific receptor, which in turn could be part of a family of receptors distributed throughout the body. Moreover, the 1990 study found that the same THC receptor is also found in fruit flies – meaning the receptor gene was present in early evolution, which suggests that it serves an important biological function. At the time, however, not much more was known about this mysterious receptor.

But Wait – What is a Cannabinoid?

cannabinoids are a class of chemical compounds that act on cannabinoid receptors
Let’s take a step back for a moment. Before we answer the question, “what is the endocannabinoid system?,” it is crucial to understand what cannabinoids are.

Simply put, cannabinoids are a class of chemical compounds that act on cannabinoid receptors.

THC (tetrahydrocannabinol), the psychoactive cannabinoid typically associated with the “high” experienced after consuming some varieties of cannabis, was first isolated in 1964 – 24 years after the discovery of the non-intoxicating cannabinoid CBD (cannabidiol).1 THC and CBD are believed to be the two most prevalent phytocannabinoids (cannabinoids found in plants) in cannabis, but they are far from being the only ones in existence. In fact, over 120 cannabinoids have been extracted from the cannabis plant to date, most of which only occur in trace amounts.2<

While researchers are only just beginning to understand how THC and CBD interact with our bodies and the medical applications they may have, research is very limited on the other 118+ cannabinoids.

The Endocannabinoid System: Cannabinoid Receptors

After researchers in the aforementioned study identified the DNA sequence for the THC-sensitive receptor in rats, they were able to genetically modify a rat to remove this receptor. They then observed that, when given THC, the modified rat exhibited no psychoactive response. Since the THC had nothing to bind to, it had no effect on the rat. Thus, it was proven that THC works by binding to a specific type of receptor. These came to be known as CB1 receptors.

Later, in 1993, a second type of cannabinoid receptor was discovered. Unlike CB1 receptors, which are primarily concentrated in the brain and central nervous system (CNS), these receptors were found to be mostly located throughout the immune system (spleen, tonsils and thymus), gastrointestinal system and peripheral nervous system (PNS).3

These findings begged the question, why do we have receptors designed specifically for cannabis?

The Endocannabinoid System: Endocannabinoids

Anandamide was the first endocannabinoid discovered in 1992 by a group of researchers led by Israeli scientist Dr. Raphael Mechoulam
The truth is, our CB1 and CB2 receptors weren’t designed for cannabis; it just so happens that phytocannabinoids in cannabis bind to them. As it turns out, our body produces its own cannabinoid-like compounds, which came to be known as endocannabinoids.

The first endocannabinoid was discovered in 1992 by a group of researchers led by Israeli scientist Dr. Raphael Mechoulam. Interestingly, this endocannabinoid was found to bind to the same cannabinoid receptors as THC. Because of its role in modulating mood (among other functions), the endocannabinoid was named anandamide – the Sanskrit word for bliss. More recently, scientists have discovered that running and eating chocolate both boost the body’s levels of anandamide, giving a whole new meaning to the term “runner’s high.”

A second endocannabinoid was discovered in 1995, again by Dr. Mechoulam’s team. It was dubbed 2-arachidonoyl glycerol or 2-AG for short.

Piecing it All Together: What is the Endocannabinoid System?

To summarize, the Endocannabinoid System (ECS) is comprised of a network of receptors (CB1 and CB2) located throughout the body and the endocannabinoids that bind to them.

While THC binds directly to these receptors, CBD – and potentially other cannabinoids – do not. More research is required to determine how exactly CBD interacts with the ECS.

In recent years, the ECS has been found to play a much larger role in our biological functions than initially thought. The ECS regulates such diverse processes as appetite, mood, pain and sleep.4

Now, the next time someone asks you “What is the ECS?” you can educate them about the broad range of roles it plays in our bodies.

1. Gaoni Y, Mechoulam R. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish. Journal of the American Chemical Society. 1964;86(8):1646–1647.

2. Morales P, Hurst DP, Reggio PH. Molecular Targets of the Phytocannabinoids: A Complex Picture. Progress in the Chemistry of Organic Natural Products. 2017;103:103–131.

3. Dhopeshwarkar A, Mackie K. CB2 Cannabinoid receptors as a therapeutic target-what does the future hold?. Molecular Pharmacology. 2014;86(4):430–437.

4. Alger BE. Getting high on the endocannabinoid system. Cerebrum: The Dana Forum on Brain Science. 2013 Nov-Dec; 2013: 14.