The Endocannabinoid System - Our Biological Bond to Cannabis


If you’ve been immersed in the world of cannabis for a while, you’ve probably heard mention of the human Endocannabinoid System, or ECS. If you don’t know much about what that is, or how cannabis interacts with it, you’ve come to the right place!

In this article, we’ll break down the emerging (and often confusing) science surrounding the Endocannabinoid System, explaining key terms and illuminating how cannabis naturally interacts with our bodies at a cellular level to encourage improved health and overall wellness.

Part 1: What is the ECS, and Why Didn’t My Biology Teachers Ever Mention It?

At its most basic definition, the Endocannabinoid System (which we’ll refer to as simply “the ECS” from here on out, for the sake of brevity) is a specialized group of receptors present in tissue cells all throughout your body, including cells of the nervous system, muscular system, digestive system, immune system - quite literally every bodily system you learned about in your early Biology classes. In fact, although we are still learning lots of new information about its full scope and action at this time, scientists already believe the ECS is the largest signaling system in the human body.

Studies have shown that the ECS functions by interacting with cannabinoid molecules to modulate many chemical signaling pathways in the body in order to encourage healthy equilibrium in a wide variety of bodily processes. You can think of your ECS and related compounds like the motor oil in your car - it keeps all of the vital components working at top efficiency, and helps prevent wear and tear over time, which manifests in our body as disease or health disorders. The ECS is particularly effective at managing a wide range of processes because it can flexibly function to either increase or decrease a chemical signal based on the variance from “baseline” equilibrium at a given time - so it can down-regulate a chemical signal that is overactive, or up-regulate a chemical signal if it is underactive. This generalized “maintenance” action of the ECS on essentially all of our important bodily processes may explain why cannabis medicine is so effective for the management of many diseases that do not typically respond to other treatments, as explained in a 2008 study and 2016 follow-up by Ethan Russo, one of the foremost cannabis researchers and educators of this generation.

So you may be wondering - if the ECS is so widespread and vital to human health, why didn’t my Biology teachers ever tell me about it? The sad truth of the matter is that the ECS has long been viewed, and to a great extent is still viewed, as taboo in the academic and medical worlds due to its close ties to cannabis. Even medical doctors are not typically taught about the ECS at all during their training.

This burying of the truth about the ECS grew from two sources - firstly, the ECS was not discovered until the fairly recent 1980-1990s, when concurrent research by the respective teams of cannabis researchers Raphael Mechoulam (the Israeli chemist who first identified THC and CBD in the 60s) and Lisa A. Matsuda, a molecular biologist working in Washington D.C., among others began deepening our understanding of the individual components and mechanisms of the ECS. Secondly, due to widespread prohibition of and propaganda against cannabis in the Western world, once the ECS was identified, it was not immediately legitimized - why would doctors spend time learning about a bodily system that seemed to interact with an illegal drug, which the government claimed was a dangerous menace to society? Almost no well-respected academic institutes in the US dared conduct cannabis or ECS research openly for fear of losing access to federal funding and grant opportunities, so the ECS went largely untaught to the medical and scientific communities - much to the detriment of medical science and public health, as we are now seeing through the spreading effective use of medicinal cannabis.

Thankfully, the tides are turning for research on cannabis and the ECS, and teams of researchers around the world are looking at new ways that interactions between cannabis and the ECS can be used for the betterment of our health and wellness.

Part 2: How Does Our ECS Interact with Cannabis Compounds?

It may be surprising to learn that your body has specialized receptors that interact with the active compounds in cannabis - it’s almost as if we were made specially for each other! What’s even more surprising is the fact that the ECS not only interacts with cannabis compounds like THC and CBD, but that our bodies actually produce their own natural versions of these cannabinoids! It’s true, and it’s believed that the cannabinoids produced by cannabis - called Phytocannabinoids (phyto meaning “plant-derived”) - function so well as ECS modulators because of their similarity in structure to our own endogenous (internally produced) cannabinoids, or Endocannabinoids. The main endocannabinoids are Anandamide and 2-AG , both of which are produced on demand by the body to maintain homeostasis, or equilibrium, of the bodily processes. Anandamide is somewhat similar to THC - the action of anandamide results in positive, uplifting feelings and the compound is produced readily during exercise, explaining the mood elevation associated with physical activity. 2-AG functions indirectly on the ECS to modulate equilibrium, and as such is more similar to CBD. Normal functional levels of these endocannabinoids are associated with good physical health and mood. However, these endocannabinoids can be prematurely degraded by the effects of chronic stress, or may even be underproduced by the body and unable to take effective action.

In fact, cannabis research scientists believe that many diseases, especially those in the autoimmune family, are actually the result of chronic endocannabinoid deficiency, in which your body doesn’t naturally produce enough of your own endocannabinoid compounds to keep your health at equilibrium, and may benefit from supplemental treatment with cannabis-derived phytocannabinoids. Author and cannabis coach Dr. Michele Ross discussed this condition on her episode of the Periodic effects podcast in great detail, so be sure to listen to that episode if you’d like a deep-dive on the mechanisms behind chronic endocannabinoid deficiency and how to manage it. Let’s take a closer look at the similarities between our own endocannabinoids and the phytocannabinoids found in cannabis to better understand how our bodies are naturally keyed for cannabis medicine.

You’re likely familiar with the major cannabinoids THC and CBD - THC (or tetrahydrocannabinol) being the primary cannabinoid of drug cultivar cannabis which produces euphoric psychoactive effects, and CBD (or cannabidiol) being the more therapeutic cannabinoid gaining popularity for medicinal applications without heavy psychoactive effects. There are many more minor cannabinoids that we are just starting to understand through new scientific research, but we’ll concentrate on these 2 main cannabinoids for this article. These phytocannabinoids are ingested when consuming cannabis products and enter the bloodstream, where they are distributed throughout the body and interact with the specialized receptors of the ECS on many tissues - THC has a direct interaction with ECS receptors similar to the action of anandamide, and CBD has a more indirect influence on modulating chemical processes similar to 2-AG. To better differentiate these two processes, let’s look at the specific types of ECS receptors and how they connect to these cannabinoids.

There are two main ECS receptor types that we’ve identified as interacting most strongly with cannabinoids - the CB-1 and CB-2 receptors. Other ECS receptors are speculated to exist, but have not been as well-studied as CB-1 and CB-2, so we’ll focus on these two receptors here. The CB-1 receptors are primarily found in the cells of the brain and central nervous system, with some lower concentrations in certain organs and muscle tissues. CB-1 receptors are the main target of THC binding, leading scientists to believe that this interaction is the primary source of cannabis intoxication effects. Additionally, the binding of THC to CB-1 receptors down-regulates the perception of pain, which may explain why many patients have found cannabis to be an effective treatment for chronic pain conditions. But THC is not the only phytocannabinoid that influences the CB-1 receptor - CBD is also able to change the binding ability of CB-1 receptors indirectly, forcing the release of THC from the receptor’s binding site. This is why a dose of CBD is typically effective at reducing intense cannabis experiences associated with THC “overdose”. “Overdose” is placed in quotations to highlight the fact that while a high dose of THC may certainly be uncomfortable to experience, it is in no way lethal or harmful in the long term. This is due to the fact that there are not high CB-1 receptor concentrations in the regions of the brain controlling important autonomous bodily processes like respiration and heart rate, and as such THC cannot disrupt these processes and cause death like certain other drug overdoses will.

While CB-1 receptors are primarily concentrated in the central nervous system, CB-2 receptors are much more widespread throughout bodily tissues - being found abundantly in the tissues of the immune system, peripheral nervous system, digestive system, and several other locations. These receptors are not concentrated in the brain or keyed to bind to THC, and as such are not tied to the psychoactive effects of cannabis. Instead, these receptors function primarily in therapeutic maintenance of the body’s immune responses, including reducing inflammation and other similar overreactions in the body. CBD loosely associates to CB-2 receptors to assist in modulating bodily processes up or down, explaining the basis of the mechanism behind CBD’s widespread medicinal applications.

Image credit:  Hemple

Image credit: Hemple


Part 3: How Does Our ECS Directly Impact Our Health?

So now that you understand that the active compounds in cannabis interact with our ECS receptors to illicit changes in the strength and frequency of chemical signaling pathways, we’ll discuss what that actually means in terms of our health and how we perceive cannabis as an effective medicine.

In order to better understand how our ECS is directly tied to our health, it’s best to look at a couple of well-researched examples of how different cannabinoid-ECS interactions can treat certain ailments. For example, one of the most common applications of cannabis medicine is in the treatment of diseases caused by types of rogue inflammation - including arthritis, colitis, multiple sclerosis, and others. The inflammation in different cell locations registers as pain, discomfort, and/or disruption of normal bodily processes. The modulating action of cannabinoids are able to disrupt the chemical pathway that is causing chronic inflammation, essentially “turning off” the mechanism inducing the inflammation and relieving the associated symptoms patients experience.

One of the most talked-about medicinal applications of cannabis medicine in recent years is the anti-spasmodic, or anti-seizure, effects of cannabis oil high in CBD. CBD is particularly effective at modulating and interfering with the runaway chemical pathways that cause seizures and spasms, both in the form of full-body convulsions and localized muscle spasm disorders. Cannabis medicines have been used in the treatment of epilepsy and seizures reaching back to ancient history, so although the science is just now starting to catch up on this front, we have known about this medicinal effectiveness through anecdotal evidence for centuries.

As we briefly mentioned before, cannabis has been used as an effective medicine for the treatment of many chronic pain conditions. Chronic pain is notoriously difficult to treat, as pain is hard to quantify and study, it can generate from many different sources and pathways, and it can be localized or diffuse or modulate between the two. This wide range of symptom types and causes makes it hard for medical professionals to pinpoint the best treatment for a certain patient’s needs. However, cannabis seems to function well for many different pain conditions, including migraine, endometriosis, fibromyalgia, and other pain conditions with vastly varied root causes thanks to its generalized action toward homeostasis.

A well-known side effect of recreational cannabis consumption is feelings of sedation and sleepiness, leading to the stereotype of the “lazy stoner”. However, this is also one of the most potentially beneficial aspects of medicinal cannabis with the ability to help the greatest number of people around the world, as sleep disorders are increasingly common in our busy and hectic societies. Increased ECS signaling in the central nervous system has been shown to modulate sleep, so supplemental THC dosing at night can be quite effective for helping patients fall asleep effectively and stay asleep throughout the night. Additionally, there’s evidence suggesting that cannabis therapy is useful for modulating dream cycles, offering relief for those plagued by nightmares, especially associated with PTSD.

Conclusion: We’ve Come a Long Way, But Have Much Yet To Learn

Clearly, the many unique interactions between active cannabis compounds and our natural Endocannabinoid System are capable of producing a wide array of beneficial effects for our health and wellness, and this is just what we’ve learned in the last 30 years as the shroud has started to lift from cannabis research. Leaps and bounds have been made in understanding the cellular mechanisms that allow cannabis to help our bodies maintain optimal health in this short time; it is almost guaranteed that scientists will soon begin to identify entirely novel medicinal mechanisms within the ECS that we never dreamed possible back when THC and the CB-1 receptor were first found.

Exciting developments are on the horizon as legalization and medicinal research spread across the globe and gain acceptance - we’ll be sure to revise this article with new discoveries and corrections on existing theories as we become aware of them.

To keep up with the latest in cannabis science news, be sure to subscribe to our podcast Periodic effects for interviews with the leading voices in cannabis research and education.