Endocannabinoid System

Medically reviewed by Bryan Doner, MD, and Cannabidiol Life’s Medical Review Team.

Ever wonder how phytocannabinoids like CBD, CBG, CBC, CBN, and THC work?

To get right to it, these cannabinoids interact with an internal biological system known as the Endocannabinoid System, ECS, for short. 

If you’ve never heard of it, don’t worry, it’s fairly new in terms of being accepted into the medical society as it wasn’t until 1992 that this system was documented and named.

When The ECS Was First Discovered

In 1988, the government-funded United States study at St. Louis University School of Medicine officially documented and scientifically proved that mammals (humans, etc) have receptor sites that respond to the chemical compounds found in cannabis.

In 1990, a team led by Lisa Matsuda at the National Institute of Mental Health in the United States mapped the DNA sequence that encodes cannabinoid receptors in the brain. This study was eye-opening and led to G-protein-coupled receptors, called endocannabinoids, like CB1 and CB2 to be directly identified.

CB1 is a dominant receptor in the brain, responsible for signaling to the rest of the ECS once influenced by cannabinoids. CB2 is a second receptor, mostly located in the immune and peripheral nervous systems.

In 1992, at the Hebrew University in Jerusalem, Dr. Lumir Hanus along with American researcher Dr. William Devane discovered other endocannabinoids like 2-AG, 2-AGE, DEA, and NADA. These scientific discoveries gave light on the complex metabolic pathways and interactions between phytocannabinoids and endocannabinoids.

This molecular signaling system was called,

The Endocannabinoid System.”

What Is The Endocannabinoid System?

The ECS is a complex biological system in the human body that has cell receptor sites that respond to the chemical compounds (phytocannabinoids) found in cannabis and hemp plants.

These cannabinoid receptor sites serve as neurotransmitters of information and interact directly or indirectly with several major biological processes.

In the past, experts have proclaimed, “…there is much more yet to be discovered.”

Almost All Living Organisms Have It

According to this study published on the NIH website, mammals, reptiles, birds, fish, and invertebrates all contain an ECS. This system appears to be vital for the progression of all walks of life with only a handful of species that don’t have an ECS.

Let’s take a look at some of the most recent findings in regards to the functions and role of the ECS.

It's Role In The Body

According to this study published in May of 2022, it states that the ECS is both operational and a crucial modulator within the following biological systems found in the human body:

  • Central Nervous System
  • Autonomic Nervous System
  • Human Endocrine System
  • Immune System
  • Reproductive System
  • Gastrointestinal
  • Micro Circulation

The primary role of the ECS is to maintain the proper individual functioning of the above-mentioned biological systems by maintaining stable communication across and between each of these systems.

In essence, the ECS promotes homeostasis within the body.  

Support for this statement comes from UCLA’s Center For Cannabis And Cannabinoids.  They state on their website that the main function of the Endocannabinoid System appears to be maintaining bodily homeostasis.

How Does Cbd Promote Homeostasis?


The best definition we found on Homeostasis that shares both its importance, as well as a clearcut, comprehensive description, was found on Britannica.
Thus, we will quote them word-for-word.

Homeostasis defined by Britannica.com

“Homeostasis is any self-regulating process by which biological systems tend to maintain stability while adjusting to conditions that are optimal for survival. If homeostasis is successful, life continues; if unsuccessful, disaster or death ensues. The stability attained is actually a dynamic equilibrium, in which continuous change occurs yet relatively uniform conditions prevail.“

When our body experiences pressure from outside it can synthesize CBD, CBG, CBN, THC, etc to help the ECS work against these stressors.

Homeostasis in the human body is the desire of our internal systems – organs, bones, muscles, neural pathways, etc. to communicate with each other perfectly and promote a completely balanced management system.

For example, our body works hard to maintain the correct internal temperature (98.6 degrees) and the correct blood sugar and blood pressure levels (80-120). This is because our cells have to be in the right environment to execute correctly. Cells make up every part of the body so this is extremely important.

By stimulating and supporting your Endocannabinoid System for perfect functioning, one could find relief from many irritating daily wellness inconveniences. 

The Three Main Parts

  • Let’s look closer at the parts of the Endocannabinoid system to better clarify and comprehensively explain with more accuracy what the ECS actually does

  • The Human Endocannabinoid System is primarily composed of three parts:

CANNABINOID RECEPTORS: these receptors are present on the surface of cells and when it comes to association with Phytocannabinoids (Phyto = plant-derived), these cannabinoid receptors are commonly broken down into two categories; CB1 & CB2 receptors

ENDOCANNABINOIDS – also called endogenous cannabinoids (cannabinoids naturally found within the human body) are chemical compounds/molecules that communicate or activate the above receptors

METABOLIC ENZYMES – proteins that break down and reuptake the phytocannabinoids and endocannabinoids once they have activated the receptors

Cannabinoid Receptors

In the endocannabinoid system, cannabinoid or phytocannabinoid receptors are located on the surface of the cells. These receptors play an important role in monitoring the body’s internal environment for changes. They send any info about changing conditions to the inside of the cell which will relay this information to promote the necessary cellular response to counteract the change.

In the ECS and CNS, the two most known and studied cannabinoid receptors are CB1 and CB2 (CB literally stands for cannabinoid).

Another interesting fact is that CB1 receptors are some of the most numerous receptors in the human brain and the ones that get you high! CB2 receptors come more into play in the immune and nervous systems.

Endocannabinoids stimulate presynaptic and postsynaptic nerve endings in both systems and relay information from the brain through the spinal cord to the rest of the body.

The Endocannabinoid System Regulates The Nervous System Via Cb1 &Amp; Cb2 Receptors


Endocannabinoids are molecules produced naturally in the human body that activate the above receptors. Our body naturally produces many endocannabinoids when they are needed and exposed to phytocannabinoids, but the two main ones are anandamide or N-arachidonoylethanolamine (AEA) and 2-ArachidonoylGlycerol (2-AG).

These endocannabinoids are produced in our cell membranes. Anandamide is a fatty-acid neurotransmitter often referred to as the “bliss molecule.”. 2-ArachidonoylGlycerol (2-AG) is present mostly in the central nervous system (CNS) and has been seen to be naturally occurring in maternal cow and human milk.

Metabolic Enzymes

The third main component of the endocannabinoid system is the metabolic enzymes that destroy endocannabinoids once they are used, called reuptake. The metabolic enzyme that breaks down AEA is called Fatty acid amide hydrolase (FAAH). The enzyme protein responsible for getting rid of 2-AG is called Monoacylglycerol lipase (MAGL). Just like other aspects of cell function, these enzymes are very essential because they make sure all endocannabinoids are fully used when needed.

Endocannabinoids are quite unique from other molecular signals like hormones and neurotransmitters because:

They don’t transmit signals that last longer than needed

They don’t get repackaged for later use by the cell; they are created on an as-needed basis

Almost all of our body’s organs and systems contain these three components of the ECS. They all also generally help in some way to regulate homeostasis, even if not directly stimulated by phytocannabinoids. Now that we know the integral parts of the endocannabinoid system, let’s look at how they work together to regulate homeostasis in the nervous system and the immune system’s inflammatory response.

Gunduz-Cinar O, Hill MN, Mcewen BS, Holmes A. Amygdala FAAH, and anandamide: mediating protection and recovery from stress. Trends Pharmacol Sci. 2013;34(11):637-44. [PDF]

Ligresti A, De Petrocelli’s L, Di Marzo V. From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology. Physiol Rev. 2016;96(4):1593-659. [PDF]

Endocannabinoid Regulation

As briefly touched on in section 2 of this article (What Is The Role Of The Endocannabinoid System), we believe it is pertinent to dive in just a little deeper on two of the specific roles; the Nervous System and inflammation.

We are targeting these two specifically because they have a very strong impact on keeping our bodies in homeostasis. Further, when either of these regulatory management systems is out of whack, health issues and concerns are sure to follow.

Central Nervous System

Our brains work by sending electrical signals or impulses through neurons. Each neuron interacts with another like a chain and relays information to the body. Ever been over stimulated? Well, neurons in the brain can experience similar situations and this is where endocannabinoids can come to the rescue. Endocannabinoids stop neural aging and toxicity by lessening overwhelming and overloading signals.

When a neuron becomes overwhelmed endocannabinoids will interact with the neural pathway through its CB1 receptors. CB1 will instruct the neuron to lessen its transmitting signal or quiet down. This function allows receiver neurons to regulate the amount of information they are receiving. An important and interesting thing to note here is that endocannabinoids actually work in reverse (the signal they send is called “retrograde”).


Inflammation is actually a necessary and preventative response by our body’s immune system. When we have an infection or get physically injured, fluid builds up to remove germs and damaged cells from the site of trauma. The body’s use of inflammation is sometimes though less than ideal. Inflammation can spread to other areas beyond where it is needed, and it can also last longer than it is needed. This is often due to nerve damage or some underlying health condition like autoimmune diseases activating the response inappropriately.

Endocannabinoids have been shown to apparently stop or limit the immune system’s inflammatory signals. They release just like other immune cells in response to damage, and they function similarly to how they do in the brain – by limiting the inflammatory response and immune response so that it isn’t overwhelming.


Wilson RI, Nicoll RA. Endocannabinoid signaling in the brain. Science. 2002;296(5568):678-82. [PDF]

Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333-49. [PDF]

Endocannabinoid Defiency (CECD)

Just like how our bodies can become naturally deficient in vitamins and minerals, some clinical studies have even identified Endocannabinoid Deficiency or CECD, where endocannabinoid levels may vary wildly.

While still a theory, it is believed and backed by some research that if our body does not produce high enough levels of endocannabinoids naturally, it may lead to certain conditions. Endocannabinoid dysfunction may contribute to:

  • Migraines
  • Fibromyalgia
  • Irritable bowel syndrome

More research is needed but this is especially interesting because these conditions currently have no clear underlying cause, they are not really treatable, and they may develop together.

Final Thoughts

Imagine the possibilities if supplementing phytocannabinoids actually helped stop CECD!

When we look at the Endocannabinoid system, it is clear to see that supporting this complex system of cannabinoid receptors, endocannabinoid molecules, and metabolic enzymes is vital for biological harmony.

And behind all this science, it’s clear, to us at least, that there is a strong argument for trying CBD. Such a conversation should be discussed with a Medical Marijuana Doctor and healthcare professional.

We recommend supporting your ECS with the most popular CBD products on the market like CBD oil and CBD gummies. However, just like vitamin use, it’s best to have a clear reason for taking the product beyond simply following the trend of others. If you’ve done your own research and are considering CBD for your anxiety or pain, this is perfectly understandable and in my opinion, very justifiable.

What do you think? Please leave your comments below.

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