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 so well?

The quick answer is that these cannabinoids interact with our internal biological management system known as the Endocannabinoid System, ECS, for short.  This system is so important that ProjectCBD.org has called it the body’s master regulatory system.

If you’ve never heard of the ECS before, don’t feel bad, many traditional medical professionals still don’t know about it either. HighTimes.com corroborates this stating how many traditional physicians still don’t know about its vital role in managing and establishing internal balance within our bodies.

The History Of The Endocannabinoid System: Past To Present Day

  • The Marijuana Tax Act of 1937 effectively banned the use and sale of Marijuana.

  • 33 years later, the non-negotiable ban on the use of Marijuana was changed with the passing of The Controlled Substances Act of 1970 (CSA). This ACT gave the U.S. Government the power to regulate and control a person’s diet by forbidding the use/consumption of harmful man-made narcotics and substances. Unfortunately, this also applies to any possible therapeutic or medicinally beneficial herb or plant that was naturally grown in the wild. This ACT permits the United States government to control your diet

  • In 1988, in a government-funded study at the St. Louis University School of Medicine, Allyn Howlett and William Devane found receptor sites in the brain that responded to phytocannabinoids found in cannabis.

  • In 1990, a team led by Lisa Matsuda at the National Institute of Mental Health mapped the DNA sequence that encodes cannabinoid receptors in the brain. This study was eye-opening and led to the identification of CB1 and CB2 receptors.

  • On March 24, 1992, Dr. Lumir Hanus and Dr. William Devane discovered and isolated the first known endocannabinoid in the human brain and they named it Anandamide, a Sanskrit word for joy or bliss. Anandamide is also referred to as “the bliss molecule.” This new finding prompted the need to give this endogenous cannabinoid system a name which they officially 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 either react to various changes in the body or get triggered by the presence of specific chemical compounds derived from Cannabis, Marijuana, and Hemp plants known as Cannabinoids.

These cannabinoid receptor sites serve as neurotransmitters of information and interact directly or indirectly with several major biological processes. Experts have proclaimed, “…there is much more yet to be discovered.”

Almost All Living Organisms Have It

According to this 2019 study published on the National Institutes of Health (NIH) website, mammals, reptiles, birds, fish, and invertebrates all contain an ECS. Further, it claims that the ECS appears to be vital for the progression of all walks of life.

There are only a handful of species that do not have an ECS, and this is mainly due to the fact that these species lack a cellular structure with an enclosed nucleus.

Powerful Statements From Medical Professionals

Dr. Ethan Russo, Board-Certified Neurologist & Psychopharmacology Researcher offered his expertise and opinion on the importance of the ECS and specifically, the unforgivable breach of scientific trust by not teaching all medical professionals about the ECS.

You can find the full interview on Leafly.com, a well-renowned Cannabis Education website.

Here’s what Dr. Ethan Russo had to say in four separate statements.

The idea of not educating doctors on the ECS is incomprehensible because it is fundamental to how our bodies work.

Failing to address ECS education appropriately is an unforgivable breach of scientific trust and a major disservice to the public’s health

A prime example is that there are more cannabinoid receptors in the brain than there are for all of the neurotransmitters put together. 

Everything in the body is connected, and this (Endocannabinoid System) is the glue.

The ECS Is Comprised Of Three Main Parts

The Endocannabinoid System is primarily composed of three parts:




Cannabinoid Receptors

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

Located on the surface of our cells, these receptors play an important role in monitoring the body’s internal environment for changes.

If a change occurs, the cannabinoid receptors will send any info about the changing conditions to the inside of the cell, the purpose of this relayed information is a call to action in order to trigger the necessary cellular response to counteract the change and maintain homeostasis.

CB1 and CB2 Receptors: Most Common & Most Studied

The CB1 and CB2 receptors are undeniably the most known and studied cannabinoid receptors in the ECS. Here are a few key facts you should know about them:

  • CB1 is a dominant receptor in the brain that is responsible for sending signals to the rest of the ECS once influenced by cannabinoids.

  • CB1 is the most abundant receptor in the brain.

  • CB1 is responsible for making you feel high after consuming THC.

  • CB2 is mostly located in the immune and peripheral nervous systems.

Cannabinoid receptors are comparable to a biological information delivery service. Once the information is received by the brain, the brain will tell the body to either upregulate or downregulate the current amount of available endocannabinoids within the body.


Also called endogenous cannabinoids (cannabinoids naturally produced within the human body), stimulate presynaptic and postsynaptic nerve endings.

This helps relay information from the brain, through the spinal cord, and to the rest of the body.

Our body naturally produces endocannabinoids when needed or when exposed to phytocannabinoids. Once cannabinoid receptors notice the presence of phytocannabinoids in the body, the following endocannabinoids are either triggered for mass production or scaled down:

  1. Anandamide or N-arachidonoylethanolamine (AEA), is a fatty-acid neurotransmitter often referred to as the “bliss molecule.”
  2. 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 which are proteins that break down and destroy the endocannabinoids once they have been activated, used, or no longer needed. This enzymatic process is called reuptake.

  • The metabolic enzyme in charge of breaking down AEA (Anandamide) is called Fatty acid amide hydrolase, also known as FAAH.

  • The metabolic enzyme protein responsible for getting rid of 2-AG is called Monoacylglycerol lipase, MAGL for short.

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 what the ECS is, its general purpose for managing several biological systems, and the three integral parts that keep the ECS running smoothly, let’s take a look at several accredited scientific studies that expand on the specific biological systems that the ECS is involved in regulating.

The Main Purpose & Functional Role of the ECS

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

  1. Central Nervous System

  2. Autonomic Nervous System

  3. Human Endocrine System

  4. Immune System

  5. Reproductive System

  6. Gastrointestinal

  7. Micro Circulation

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

In essence, and according to UCLA’s Center For Cannabis And Cannabinoids, the main function of the Endocannabinoid System appears to be maintaining bodily homeostasis.

Homeostasis: Defined & Explained

How Does Cbd Promote Homeostasis?

Homeostasis, in regards to the Endocannabinoid System, can be informally defined as the human body’s natural desire to keep communication open between our internal systems – organs, bones, muscles, neural pathways, etc. and promote a completely balanced management system.

On Britannica.com, an internationally recognized and well-respected online encyclopedia, we found a more authoritative definition and answer to the question…

What Is Homeostasis?

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.
– Encyclopedia Britannica

By stimulating, activating, and supporting your Endocannabinoid System via the consumption of phytocannabinoids, it seems like everyone has a winning chance, or at minimum, a new opportunity to experience what life is like when you have a perfectly functioning ECS and a body that is blissfully balanced from the inside out.

The questions now are:

  • What happens to your body when your ECS is not functioning properly?

  • Can low endocannabinoid levels negatively impact your overall health?

Let’s talk, Endocannabinoid Deficiency!

Endocannabinoid Deficiency (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 diseases or mild to severe health 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

Could Fibromyalgia, IBS, severe headaches, and migraines be the result of a poorly functioning ECS due to low endocannabinoid levels?

Only time and more research will tell.

Summary & 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.

  • Pertwee. Roger. G. (2006). Cannabinoid Pharmacology: the first 66 years. British Journal of Pharmacology. Vol. 147. Pages 163-171.



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