Home » Cannabis, Psilocybin & Psychedelics Info » What is The Endocannabinoid System?
The endocannabinoid system what is it?

What is The Endocannabinoid System?

Talking about the benefits of cannabis without mentioning the Endocannabinoid System (ECS) is almost impossible. And it is implied in every discussion about the benefits of cannabis. The ECS is at the heart of why cannabis effectively treats and alleviates such a wide range of symptoms and illnesses. 

We have touched on the ECS in past articles like ‘What is CBD Oil?’. Now is a good time to take an in-depth look at this fascinating 600 million-year-old internal body system that cannabis helped scientists discover … in the 1990s. 

ECS Basics

To start, the endocannabinoid system is an essential endogenous (internal) body system, like the circulatory or nervous system. And like these systems, the ECS is a natural internal system. Therefore, some researchers drop the prefix and call it the cannabinoid system.

Second, the cannabinoid system (ECS) existed before our first contact with phytocannabinoids from cannabis or other plants. Specifically, this is because it has evolved over 600 million years. In fact, all known animals on earth but insects have an ECS. 

Finally, our bodies make their own cannabinoids. For example, the opioid system was instructing the body to produce and release endorphins before exogenous (external) opiates were discovered. And the same is true of cannabinoids and the ECS. In the same way, our bodies produced their own version of THC (called AEA) before the first known use of cannabis.

What Does the ECS Do?

The ECS acts across all body systems. It maintains homeostasis (balance) between the body’s interrelated systems and the external environment. That is an extremely big job with a lot of moving parts.

Dr. Rachel Knox, M.D., a medical practitioner who focuses her work on the ECS, explains:

“There is not a single function in your bodies that is not somehow influenced or modulated by the ECS. It behaves like a switchboard, functioning in and across all physiologic processes and organs, acting and reacting to internal and external stimuli, to direct, correct and overall manage your health.” (Knox, 2019).

Balance Across All Systems

This broad involvement has the ECS involved in our reward and learning systems, memory, cognition, immunity, and so much more. 

With the wave of legalization and the slow removal of the harmful legacy of propaganda against cannabis, scientists are finding greater freedom to study the ECS. It was, after all, by studying cannabis that scientists discovered this crucial body system.

How Was the Endocannabinoid System Discovered?

The ECS is a 600 million-year-old essential regulatory system that was not discovered until the 1990s. 

Scientists attempting to understand the workings of THC, the psychoactive cannabinoid, discovered the ECS using radio-tagged THC. This tagged THC could then be observed as it cascaded through the body. 

Observed locking into an extensive receptor network, THC worked throughout the brain and the rest of the body. This extensive receptor network is the ECS.

How Does the ECS Work?

This research revealed a new understanding of THC. It was discovered that it is a direct analog or mimicker, of a ligand produced by our body called anandamide (AEA). Ligands are one of three core components of the ECS. 

AEA: The Real Runner’s High Molecule!

An interesting side note here is that endorphins have long received credit for anandamide’s work as The Bliss Molecule. We have all heard of Runner’s High and endorphins, but few of us had heard of the ECS and AEA until recently. This has been due to misinformation! If you’re a runner, you are mostly getting high off your endocannabinoid system, not your opioid system.

There are about 100 other phytocannabinoids in cannabis and other plants that mimic our endocannabinoids (ligands) and have the potential to supplement or modulate the ECS in therapeutic and healing ways. 

The Endocannabinoid System has 3 Major Components

#1 Cannabinoid Receptors

Cells in the body that interact with the ECS contain cannabinoid receptors. These are sites on the cell membrane where endocannabinoids like AEA or phytocannabinoids like THC can lock in and initiate a process. 

A runner’s high or cannabis high are both examples of these types of processes. You aren’t just ‘high’: a lot of other positive things are happening! You feel euphoric, energized, creative, clear…the list goes on and how these emotions arise in some and not in others is still a fun mystery for science to solve about the newly discovered ECS.

The most well-known cannabinoid receptors in the ECS are CB1 and CB2. More will come to light soon.  

#2 Ligands

Ligands are endocannabinoids that lock into the CB1 and CB2 receptors in the ECS. They are molecules binding to cannabinoid receptor sites. Ligands help to make up a coordination complex. AEA and 2-AG are two key ligands in the ECS. Due to their complex enzymatic interactions, endocannabinoids are similar but not entirely comparable to neurotransmitters (Alger, 2013).

#3 Enzymes

Enzymes make ligands as needed. The ECS demands enzymes as it monitors internal and external systems.

The ECS also demands the degradative enzymes that break down endocannabinoids once they have been used. Scientists call this action retrograde signaling.

Why Did It Take So Long to Discover the ECS?

It’s natural to wonder why it took us so long to discover the ECS because it is so important. Honest doctors ask themselves the same thing! They also pay attention to the history and research and are pretty clear on why. 

Schedule 1 Classification

Like Knox, the esteemed addiction specialist Dr. Gabor Maté confirms these suspicions. He points out that useful research on cannabis and the ECS has been badly hindered by the Schedule 1 classification of marijuana in the USA (Maté, 2016). This is because a Schedule 1 drug has no medical benefit, by definition. 

Maté points out the Kafka-esque bind this automatically applies to cannabis research. The bind is clear in the conclusions to fascinating studies about cannabis, a small handful of which are in the references below. 

Money and funding go to research that favors patentable pharmaceutical medicines as solutions. 

Carnegie, Rockefeller, and Cannabis Criminalization

American medical history influenced the medical world against cannabis and other ancient, natural remedies embraced by human culture for thousands of years. And it took money, power, privilege, and private interests. 

At the turn of the 20th Century, Scottish-American Industrialist Andrew Carnegie and American business magnate John D. Rockefeller both had stakes in prescription pharmaceuticals. 

At this time, American medicine was based on homeopathy and herbal medicine. By comparison, it is strange to think that 100 years ago doctors were reluctant to embrace pharmaceuticals. But Carnegie and Rockefeller would work together to fundamentally shift the paradigm toward the German model for pharmaceutical drug science.

The Flexner Report, 1910

Together, they leveraged their wealth and influence, commissioning the Flexner Report in 1910. The promotion of this report would be crucial to the standardization of the American medical system. Rallying the full force of state governments, Carnegie and Rockefeller successfully spearheaded the consolidation and standardization of American medical training.

The Flexner Report would deliberately exclude holistic care practices, natural substances, remedies, and cures. Ultimately, more doctors were trained in the newly standardized manner, by textbooks produced for and by this paradigm. 

A critical mass was reached. Prescription cannabis and other herbal remedies would take on negative connotations. First, by exclusion and later by blatantly unscientific vilification. Medical cannabis and herbal remedies were now relegated to the ‘non-medical sphere. They had been displaced from their originally trusted place in medicine. 

Cannabis was one of the most prescribed medicines in the USA before it was made illegal in 1937

The biggest kick in the teeth is that US physicians had regularly prescribed cannabis to their patients well into the 20th century. Anti-cannabis legislation had been sweeping the globe for well over 100 years. In 1937, the USA officially banned its use on a federal level with the Marijuana Tax Act. Before this, cannabis had been among the top three most commonly prescribed medicines in the USA. Unfortunately, heavy taxation on cannabis dwindled its use. Doctors who formerly prescribed it now feared prosecution. Finally, the natural, therapeutic plant was written out of American pharmacopeia in 1942.

Understanding the Endocannabinoid System

Introducing the ECS to the medical community will hopefully yield widespread benefits in the years to come. And by directing funding and research towards this fascinating internal system, there are bound to be beneficial developments.



Alger, Ph.D, B. (2013) “Getting High on the Endocannabinoid System,” PMC US National Library of Medicine, Cerebrum. 2013 Nov-Dec; 2013: 14, [online] Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/ (Accessed 22 April 2021).

American Cannabinoid Clinics, PC (2020) “Be Well On Purpose,” American Cannabinoid Clinics, PC, [online] Available from: https://www.theacclinics.com/ (Accessed 24 April 2021).

Doctors Knox (2021) “A New Health Paradigm,” Doctors Knox, [online] Available from: https://doctorsknox.com/ (Accessed 25 April 2021).

Duffy, T. P. (2011) “The Flexner Report–100 years later,” The Yale Journal of Biology and Medicine, YJBM, [online] Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178858/ (Accessed 25 April 2021).

Knox, MD/MBA, R. (2019) “The endocannabinoid system and the revolution of one | Rachel Knox | TEDxPortland”, TEDxTalks, [online] Available from: https://youtu.be/oJbOQ9P2NYQ (Accessed 22 April 2021).

Lutz, B. (2007) “The Endocannabinoid System and Extinction Learning,” Molecular Neurobiology, Humana Press Inc, [online] Available from: https://link.springer.com/article/10.1007/s12035-007-8004-x (Accessed 25 April 2021).

MacDonald, A. (2020) “Teens who smoke pot at risk for later schizophrenia, psychosis,” Harvard Health Blog, [online] Available from: https://www.health.harvard.edu/blog/teens-who-smoke-pot-at-risk-for-later-schizophrenia-psychosis-201103071676 (Accessed 25 April 2021).

Marzo, V. D. (2018) “New approaches and challenges to targeting the endocannabinoid system,” Nature News, Nature Publishing Group, [online] Available from: https://www.nature.com/articles/nrd.2018.115?fbclid=IwAR0Z6LsnrPZYwn69RVuuWLN-vuVSwR-60Vy9vloR99b9Li2V-PEGG2ECBow (Accessed 25 April 2021).

Maté, Gabor, Dr. (2016) Dr. Gabor Maté – Cannabis and Addiction, Canlio, [online] Available from: https://youtu.be/k2R3_728Xxc (Accessed 25 April 2021).

Mechoulam, R. and Parker, L. (2013) “The Endocannabinoid System and the Brain,” Annual Review of Psychology  Vol. 64:21-47, [online] Available from: https://www.annualreviews.org/doi/abs/10.1146/annurev-psych-113011-143739 (Accessed 22 April 2021).

Moore, M. (2018) “How the Endocannabinoid System was discovered: Cannabis Sciences,” Labroots, Labroots, [online] Available from: https://www.labroots.com/trending/cannabis-sciences/8456/endocannabinoid-system-discovered (Accessed 26 April 2021).

National Scientific Council on the Developing Child. (2005/2014). Excessive Stress Disrupts the Architecture of the Developing Brain: Working Paper 3. Updated Edition. http://www.developingchild.harvard.edu (Accessed 25 April 2021).

Pertwee, R. G. (2006) “Cannabinoid pharmacology: the first 66 years,” British journal of pharmacology, Nature Publishing Group, [online] Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1760722/ (Accessed 25 April 2021).

Pivital Edu (2021) “Cannabinology with Confidence,” Pivital Edu, [online] Available from: https://www.pivitaledu.com/ (Accessed 24 April 2021).

Prenderville, J. A., Kelly, Á. M. and Downer, E. J. (2015) “The role of cannabinoids in adult neurogenesis,” British Journal of Pharmacology, John Wiley & Sons, Ltd, [online] Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543605/ (Accessed 25 April 2021).

Reggio, P. H. (2010) “Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown,” Current Medicinal Chemistry, U.S. National Library of Medicine, [online] Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120766/ (Accessed 26 April 2021).

Ross, Ruth, Dr. (2019) Demystifying the endocannabinoid system.: Ruth Ross: TEDxMississauga, TEDx Talks, [online] Available from: https://youtu.be/8GsmTFytBYI (Accessed 25 April 2021).

Ruehle, S., Aparisi Rey, A., Remmers, F. and Lutz, B. (2012) “The endocannabinoid system in anxiety, fear memory and habituation,” Journal of Psychopharmacology 26(1) 23–39, [online] Available from: https://journals.sagepub.com/doi/pdf/10.1177/0269881111408958 (Accessed 25 April 2021).

Wikipedia (2021) “Timeline of cannabis law,” Wikipedia, Wikimedia Foundation, [online] Available from: https://en.wikipedia.org/wiki/Timeline_of_cannabis_law (Accessed 26 April 2021).

1 thought on “What is The Endocannabinoid System?”

  1. Excellent article, very in-depth. I had no idea how little I knew about cannabis and cannabinoids before I decided to read. Thanks for taking the time to write this, I really appreciated it.

Leave a Comment

Shopping Cart