Your Body's Endocannabinoid System
If you’ve been immersed in the world of CBD for a while, you’ve probably heard mention of the human Endocannabinoid System, or ECS.
If you don’t know much about what the Endocannabinoid System is, or how CBD interacts with the receptors of the Endocannabinoid System in our bodies, you’ve come to the right place to learn about our biological bond to hemp cannabinoids!
In this article, we’ll break down the emerging (and often confusing) science surrounding the Endocannabinoid System, explaining key terms and illuminating how cannabinoids from hemp naturally interact 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) is a specialized group of receptors present in cells all throughout your body, including 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.
So if you’re wondering where the endocannabinoid system is located in your body, the answer is simple - everywhere!
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.
In this way, the ECS is responsible for conducting the balance that governs almost our entire health and wellness!
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 cannabinoid medicines might be effective for the management of many diseases that do not typically respond to other treatments. This phenomenon was explained in a 2008 study and 2016 follow-up by Ethan Russo, one of the foremost cannabinoid 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 stigmatized in the academic and medical worlds due to its close ties to illegal cannabis. Even most doctors are not typically taught about the ECS at all during their medical school training!
The ECS was not originally discovered until the fairly recent 1980-1990s, when concurrent research by the respective teams of cannabis researchers Dr. Raphael Mechoulam (the Israeli chemist who first identified THC and CBD in the 60s) and Dr. Allyn Howlett (the U.S. pharmacologist who first identified the brain receptors for cannabinoids in rats), and other scientists others began deepening our understanding of the individual components and mechanisms of the ECS.
These scientists named the new signalling system the “Endocannabinoid System” to underscore the link to cannabis, as they discovered it in pursuit of understanding the mechanisms of the plant’s intoxicating effects.
Unfortunately due to widespread prohibition of cannabis in the Western world, once the ECS was identified it was not immediately legitimized.
Almost no well-respected academic institutes in the US dared conduct 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 cannabinoids like CBD and THC.
Thankfully, the tides are turning for research on the ECS, and teams of researchers around the world are looking at new ways that interactions between cananbinoids and the ECS can be used for the maintenance of our health and wellness.
Part 2: How Does Our ECS Interact with Cannabinoids like CBD & THC?
So now that you know what the ECS does, you may be wondering what the ECS actually looks like in our body - what it’s made of, and how does the system actually work with THC and CBD.
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 cannabinoid 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 hemp - 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 very similar to THC in both structure and function in our brains - 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.
If you’ve ever felt a “runner’s high”, you’ve felt a surge of Anandamide in your brain! However, THC produces much stronger mood elevation and more psychoactive effects than Anandamide is capable of producing.
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.
Research published in early 2020 confirmed that “the ECS plays an essential role in stress responses”, and chronic stress may alter our brain’s endocannabinoid levels in conjunction with heightened anxiety.
In fact, cannabinoid 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.
Emerging research from 2019 and 2020 suggests that our endocannabinoids and the ECS play a role in managing the symptoms of a wide variety of diseases and disorders that lack traditional preventative treatments, from stroke to OCD, a chronic shortage or “deficiency” of Endocannabinoids may contribute to the appearance of symptoms.
Author and plant medicine 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 begin managing it.
Let’s take a closer look at the similarities between our own endocannabinoids and the phytocannabinoids found in hemp 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 which produces euphoric psychoactive effects and medical benefits, 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 full spectrum hemp products and enter the bloodstream, where they are distributed throughout the body and each interact with the specialized receptors of the ECS on many tissues. 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 science has currently 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.
Image Credit: Osher Center for Integrative Medicine
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 is the primary source of intoxication effects.
Additionally, the binding of THC to CB-1 receptors down-regulates the perception of sensations like temperature and pain in lab studies. 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 experiences associated with THC overconsumption.
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 cannabinoids.
Instead, these CB-2 receptors function primarily in therapeutic maintenance of the body’s immune responses, including modulating symptoms caused by 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.
Part 3: How Does Our ECS Directly Impact Our Health?
So now that you understand the active compounds in hemp interact with our ECS receptors to elicit changes in the strength and frequency of cell signaling pathways, you can begin to understand the implications for our health and how we perceive cannabinoids as a potential medicine.
Since so many common illnesses without sufficient current treatments are rooted in cellular signalling dysfunction, supporting the Endocannabinoid System may be key to reducing symptoms and improving quality of life.
In order to better understand how our ECS is directly tied to our health, explore what scientists have already said about the ECS as a target for medicinal intervention in each of the published research hyperlinks above.
Conclusion: We’ve Come a Long Way, But Have Much Yet To Learn
Clearly, the many unique interactions between active cannabinoid compounds and our body’s 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 ECS research.
Leaps and bounds have been made in understanding the cellular mechanisms that allow hemp cannabinoids 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 cannabinoid science news, be sure to subscribe to our podcast Periodic effects for interviews with the leading voices in cannabinoid research and education.
Sources Cited
Pacher P, et al. “The Endocannabinoid System as an Emerging Target of Pharmacotherapy”. Pharmacol Rev. 2006 Sep; 58(3): 389–462. doi: 10.1124/pr.58.3.2
Russo EB. “Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?”. Neuro Endocrinol Lett. 2008 Apr;29(2):192-200.
Russo EB. “Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes.” Cannabis Cannabinoid Res. 2016 Jul 1;1(1):154-165. doi: 10.1089/can.2016.0009. eCollection 2016.
Bouter Y. et al. “Chronic Psychosocial Stress Causes Increased Anxiety-Like Behavior and Alters Endocannabinoid Levels in the Brain of C57Bl/6J Mice.” Cannabis Cannabinoid Res. 2020 Mar; 5(1):51-61.http://doi.org/10.1089/can.2019.0041. eCollection 2019 Nov 13.
Scharf E.L. and Ebbert J.O. “Endocannabinoids and Stroke Prevention: Review of Clinical Studies” Cannabis Cannabinoid Res. 2020 Mar; 5(1):6-11.http://doi.org/10.1089/can.2018.0066. eCollection 2019 Apr 26.
Kayser R.R. et al. “The Endocannabinoid System: A New Treatment Target for Obsessive Compulsive Disorder?” Cannabis Cannabinoid Res. 2019 Jun; 4(2):77-87.http://doi.org/10.1089/can.2018.0049. eCollection 2019 May 29.
Barrie N, et al. “Endocannabinoids in arthritis: current views and perspective.” Int J Rheum Dis. 2017 Jul;20(7):789-797. doi: 10.1111/1756-185X.13146.
Leinwand KL, et al. “Manipulation of the Endocannabinoid System in Colitis: A Comprehensive Review.” Inflamm Bowel Dis. 2017 Feb;23(2):192-199. doi: 10.1097/MIB.0000000000001004.
Chiurchiù V, et al. “The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases.” Prog Neurobiol. 2018 Jan;160:82-100. doi: 10.1016/j.pneurobio.2017.10.007. Epub 2017 Oct 31
Rosenberg EC. et al. “Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection.” Epilepsy Behav. 2017 May;70(Pt B):319-327. doi: 10.1016/j.yebeh.2016.11.006. Epub 2017 Feb 9.
Greco R. et al. “Endocannabinoid System and Migraine Pain: An Update” Front Neurosci. 2018; 12: 172. Published online 2018 Mar 19. doi: 10.3389/fnins.2018.00172
Bouaziz J. et al. “The Clinical Significance of Endocannabinoids in Endometriosis Pain Management”. Cannabis Cannabinoid Res. 2017; 2(1): 72–80. Published online 2017 Apr 1. doi: 10.1089/can.2016.0035
Donvito G. et al. “The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain”. Neuropsychopharmacology. 2018 Jan; 43(1): 52–79. Published online 2017 Nov 8. Pre-published online 2017 Aug 31. doi: 10.1038/npp.2017.204
Murillo-Rodríguez E et al. “Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis.”. Neuroscience. 2016 Dec 17;339:433-449. doi: 10.1016/j.neuroscience.2016.10.011. Epub 2016 Oct 13.
Murillo-Rodríguez E et al. “The Endocannabinoid System Modulating Levels of Consciousness, Emotions and Likely Dream Contents.” CNS Neurol Disord Drug Targets. 2017;16(4):370-379. doi: 10.2174/1871527316666170223161908.
Elms L. et al. “Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series”. J Altern Complement Med. 2019 Apr 1; 25(4): 392–397. Published online 2019 Apr 9. doi: 10.1089/acm.2018.0437