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A Medical Marijuana Primer Part 3: The Endocannabinoid System

Written by Jeff Drake
6 · 24 · 17

The Endocannbinoid System (ECS), Simplified

This is a follow-on to my first two articles about medical marijuana. While it’s not necessary to have read parts 1 and 2 previously to benefit from this post, I recommend that you do so, if you have the time. You might also like to read another post titled, “You Think You Know Hemp?”

I am going to assume that you are familiar with or have heard of the term, “THC”, and these days you may also have heard of a chemical associated with medical marijuana named, “CBD”. You may not know what these terms mean yet, but just be aware that they are both classified by science as “cannabinoids”. That’s because these chemicals were first discovered within cannabis plants. You can move to the head of the class if you know what “CB1” and “CB2” are.

I will attempt to keep this article coherent without having to delve too deeply into all the medical science surrounding it. Rest assured I don’t claim to understand all the science behind it, but fortunately for all of us, there is a lot that continues to be written about the subject, including efforts like mine, to explain ECS using KISS (“keep it simple stupid!”). In this case, I am merely the collector and aggregator of such data and do not take credit for anything else within this paper, other than its format and the occasional comment or sidebar.


What is the ECS?

NOTE: This section got longer than I intended, but it’s important. The ECS is at the heart of medical marijuana and to know what medical marijuana is all about, you’ve got to have some understanding of what the endocannabinoid system is. I’m biased, of course, but I also happen to find the history of the science very interesting, so I include it.

I’m here to tell you that when it comes to medical marijuana, it’s all about the endocannabinoid system (ECS).  You may not have heard about it, but this newly discovered physiological system is considered by the medical community to be one of the most important medical discoveries of the last century. It’s that big a deal!

There is no need here to recount the rather infamous past of cannabis within the United States since the mid-1920’s, nor the “Reefer Madness” years. I am going to assume that the readers of this post are all aware of this history, in some cases painfully. Ironically, the National Institute for Drug Abuse (NIDA), which was so vehement in trying to prove that marijuana was as deadly as heroin or similar addictive drugs, ended up funding a number of studies about the human brain and cannabis that led to what is now called “one of the most exciting developments in brain chemistry of our time”[1] (a.k.a. the Endocannabinoid System, or ECS).

This biological system is designed for handling “cannabinoids”, which are chemicals our bodies produce. That’s right, we each are producing our own cannabis chemicals! So, what in the world is a cannabis chemical-producing system doing in our bodies? Inquiring scientists and doctors wanted to know!


How the ECS Works

Similar to earlier studies of the coca plant, in-depth research into the cannabis plant led to questions that could only be answered by turning attention to our brains. Questions like, “How is it that a plant can have such quick psychotropic impact on our brains?” “Why have there been so many reported health benefits associated with cannabis over the span of 3,000+ years?” “What’s going on between cannabis and our heads?” “What’s going on between cannabis and our bodies?”

In 1973 researchers at Johns Hopkins University, studying cocaine and opiates, discovered “receptor sites” in our brains that were capable of binding with opioids (e.g., morphine and heroin), which explained why these drugs affect us. They optimistically believed that it would only be a brief time before similar receptor sites were identified for cannabis, which would hopefully provide an explanation for why we get high from ingesting weed. Sadly, we had to wait 15 more years before any cannabis receptors were discovered!

What is a receptor site? Well, we’re talking brain chemistry here, so when it comes to understanding how our brains work, we need to remember that such communication is done via chemicals in our brain utilizing brain cells called neurons, which cause or react to changes in our brain chemistry when they are exposed to certain molecules.

It’s easiest perhaps to think of each brain cell (neuron) as a locked box. In this analogy, the neuron is the box and a “receptor” is the lock that opens the box.[2] Rest assured, great things can happen if only we can find keys that will open those boxes!

In the world of neurochemistry, the keys that fit into those receptors and unlock our neurons are chemical molecules called, “agonists”. When an agonist key opens a neuron lock, it chemically “binds” to it, which causes a chemical message to be transmitted to that cell telling it to do something.


It was work done at the St. Louis University School of Medicine that eventually led to the discovery of receptors that responded to compounds found in marijuana resin. Discovered first by Allyn Howlett and William Devane, cannabinoid receptors turn out to be far more abundant in the brain than any other type of neurotransmitter receptor! (I think that when you understand how the ECS works, it’s easy to understand why the receptors are so abundant.)[3]

Q. If the chemicals that were discovered in the cannabis plant are called “cannabinoids”, why do they call the newly discovered system the “endo”-cannabinoid system?

A. Cannabinoids and endocannabinoids are both chemicals and as chemicals, they are alike; but cannabinoids are produced by cannabis plants, whereas endocannabinoids are created by our bodies. If you think about this for a minute, it makes sense that marijuana would have such a quick and even profound impact on us humans; after all, our cells see the incoming cannabinoids (whether internally or externally manufactured) as chemicals they know and trust; and thus, perform their instructions perfectly, without argument.

So, the “endocannabinoid system” is simply the name given to a series of cell receptors that respond to specific kinds of agonists. (By the way, all mammals have an ECS.). As you shall see, the ECS is a vital physical system performing some very important work inside our bodies and we’re fortunate to have it.

In July, 1990, during a meeting at the National Academy of Science’s Institute of Medicine, Lisa Matsuda announced that she and her colleagues had successfully pinpointed the exact DNA sequence that encodes a THC-receptor. This was important news, but Matsuda followed this up with another announcement that blew her audience away, she told them that they had successfully cloned the marijuana receptor. This news was huge! Apparently, this news was so exciting because cloning the receptor was critical for scientists to more easily do further research in this area. Without the clone, further research into cannabis was stymied.

It turns out this announcement was just the opening act for what scientists proclaimed in the meeting was going to be, “The Decade of the Brain”. They weren’t wrong! More advancement was achieved in the 1990’s than in all the previous years combined.


Why Is the ECS So Important?

To put it into a nutshell, the endocannabinoid system is “…an essential regulator of bodily function in its many facets. There is hardly any physiological process that is not affected by it to some degree.”[4] Knowing this now makes it all the more remarkable that we didn’t know about this system until recently.

In 1998, Professor Di Marzo[5] declared that the basic functions of the ECS could be summarized as follows: “…relax, eat, sleep, forget and protect.”[6]

The endocannabinoid system has two primary cell receptors called, “Cannabinoid Receptor 1” (CB1) and “Cannabinoid Receptor 2” (CB2).  CB1 is the most abundant receptor found in the peripheral and central nervous system i.e., our brains – and the receptor that does the bidding of THC and affects things like our short-term memory, pleasure, pain, hunger, etc. CB2 receptors are primarily found on immune cells and tissues. When they are activated they affect inflammatory and immunosuppressive activity.

As an example of the effect CB2 can have, I can relate my own subjective experience. I have a chronic foot condition (hallux rigidus) that can inflame my foot and cause a lot of pain, so I had been taking the maximum 500mg of Naproxin daily to deal with it. While I never had any negative effects from Naproxin, I worried about long-term use, as it is very hard on your innards. I have now replaced my 500mg Naproxin with 20mg of medical marijuana. The medical marijuana pill I take is designed to provide what is known as “the entourage effect”.[7]

In my particular case, the pill I ingest has a combination of THC, CBD and some other things called, “terpenes”. Terpenes, by the way, are the essential oils in cannabis that give it its many various aromas. (All plants have terpenes). Ever open and smell a bag of weed? You’re smelling terpenes! Amazingly, the terpenes bind to receptors just like THC and CB2 do and have their own effects on us!

Right now, scientists are hard at work investigating all the various effects produced by combinations of cannabinoids and terpenes that might be used medically. Who knew, but THC as it turns out, is more important to reducing pain than CBD! Who knows what the future will bring? And I can tell you from my own experience, that when you ingest the proper combination of THC with terpenes and CBD, you can produce a medication that can be just as effective as 500mg of Naproxin, with zero negative side effects. Learning this impressed the shit out of me.

Scientists refer to the ECS as the system whose purpose is “balance”, referred to as homeostasis. When you get injured or sick, cannabinoids are used to help restore the balance. It is now believed that illnesses such as fibromyalgia and irritable bowel symptoms are caused by a dysregulated ECS.

There are, of course, more cannabinoid receptors than CB1 and CB2 and the entire concept and science is more complicated than I have depicted in this post.  My purpose is just to get you introduced to the concepts and terms.


I hope that you can, by now, begin to see that the endocannabinoid system is something special, something important. We’ve only just begun to scratch the surface of the ECS itself and the wondrous plant we call cannabis.


[1] Martin A Lee is an activist, journalist, and author who has published a number of works, including Smoke Signals: A Social History of Marijuana – Medical, Recreational, and Scientific. He is Co-Founder & Director of Project CBD, a non-profit organization he started with Fred Gardner in 2010. Lee co-authored his first book, Acid Dreams: The CIA, LSD and the Sixties Rebellion, in 1985. It explored the use of LSD during the 1960’s, including mind control experiments conducted by the CIA.

Despite his work in non-fiction literature, Lee may be most recognized for his as an investigative journalist. He was awarded the Pope Foundation Award for Investigative Journalism in 1994. Lee covered the medical cannabis movement for years in the pages of O’Shaughnessy’s, before founding Project CBD. (Source: Medical Jane).

[2] All cells have receptors and they can be found either on the surface of a cell or inside it, for example, in the nucleus.

[3] “Cannabinoid receptors function as subtle sensing devices, tiny vibrating scanners perpetually primed to pick up biochemical cues that flow through fluids surrounding each cell.” (Martin A. Lee, The Discovery of the Endocannabinoid System, pg. 1.).

[4] Introduction to the Endocannabinoid System, by Ethan Russo, MD, Medical Director, PHYTECS; pg. 1.

[5] Dr. Vincenzo Di Marzo is a Research Director at the Institute of Biomolecular Chemistry of the National Research Council (ICB-CNR) in Pozzuoli, Naples, Italy, coordinator of the Endocannabinoid Research Group in the Naples region, and an Adjunct Associate Professor in the Department of Pharmacology and Toxicology at the Medical College of Virginia at Virginia Commonwealth University in Richmond.

[6] Ibid. pg. 1.

[7] The “entourage effect” is a phrase coined by Dr. Raphael Mechoulam (a.k.a., the father of medical cannabis) and is meant to describe the effect that occurs when multiple cannabinoid compounds work in concert together to produce a, shall we say, larger or more powerful effect than if you had just ingested one chemical by itself.


Let us know what you think…


1 Comment

  1. Michael B Connolly

    Nice piece, Jeff. Greatly appreciated!


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Jeff Drake

Retired IT consultant, world-traveler, hobby photographer, and philosopher.