Endocannabinoid System 101

The endocannabinoid system, or ECS, is a complex system of receptors and lipid ligands. The purpose of the endocannabinoid system is to maintain homeostasis, or being a major regulator for the entire body. These receptors can be found almost everywhere in the human body, and extends to almost all animals on earth with the exception of insects and protozoa. The most commonly identified receptors are the CB1 receptor and the CB2 receptor. CB1 receptors are most commonly found in major parts of the brain, the central nervous system, lungs, liver, and kidneys. CB2 receptors are mostly found in the brain, immune system, and gastrointestinal system. There is hypothesized to be a CB3 receptor type (GPR55 Receptor) and up to two other receptor types, some found in cancer cells and sites of trauma in the body, but more research is needed to confirm this. These receptors have different functions as they are agonized/antagonized by endocannabinoids and phytocannabinoids. Other parts of our body are stimulated by cannabinoids, like the TRP ion channels, which include 9 different channels that are also affected by cannabinoids. stimulated by the release of endogenous cannabinoids like Anandamide. We’ll go further into endocannabinoids and how they affect our receptors later in this article. 

Table of Contents

What Are CB1 Receptor Agonists/Antagonists
What Are CB2 Receptor Agonists/Antagonists
What Are Endocannabinoids?
How Do Phytocannabinoids Interact with the Endocannabinoid System?
Endocannabinoid Deficiencies/Disorders?

What Are CB1 Receptor Agonists/Antagonists

A classic CB1 receptor agonist is Delta 9 THC. Delta 9 THC can produce euphoric effects, racing thoughts, immediate changes to one’s mental state, and even raise anxiety or amplify existing feelings. This is because CB1 receptors are primarily found in the brain and central nervous system, also giving us those immediate physiological effects. Cannabinoids can affect the CB1 receptor to varying degrees, but most psychoactive cannabinoids like Delta 9 and Delta 8 are only partial CB1 receptor agonists, or affect both the CB1 receptor and the CB2 receptor. Other cannabinoids have different effects on these receptors, such as CBD acting as a CB1 receptor antagonist in the presence of THC. This means it will have counteractive effects on the CB1 receptor as it’s being affected by THC. 

What Are CB2 Receptor Agonists/Antagonists

The CB2 receptor helps regulate our inflammatory responses and immune system. They are located within the central and peripheral nervous systems, and within white blood cells. CB2 receptors are also mainly found in the brain and gastrointestinal system. Regulating our CB2 receptors may prove incredibly helpful with conditions such as Crohn’s Disease, Inflammatory Bowel Disease, and more. CB2 receptors are also incredibly important when it comes to our perception of pain, as it regulates the peripheral nervous system, helping neuropathic pain and exhibits moderate analgesic effects for inflammatory pain. CB2 receptor agonists, like CBG or the terpene Caryophyllene, help regulate inflammation response and can also help our perception of pain by aforementioned interaction. 

What Are Endocannabinoids? 

Endocannabinoids are naturally produced compounds that interact with our ECS receptors and TRPV channels. These bind to our receptors much like THC or CBG do, and are released by our bodies only when needed. For example, some actions include exercise releases Anandamide and other endocannabinoids (responsible for the “runner’s high”). The two most notable and studied endocannabinoids are Anandamide, and 2-Arachidonoylglycerol (2-AG). 2-AG is found in human milk, and is present in high levels in the central nervous system. Anandamide is a partial CB1 receptor agonist, giving some of the same pharmacological effects as D9 THC, and 2-AG is a full agonist of both receptors which is incredibly powerful for regulating the entire endocannabinoid system. 

How Do Phytocannabinoids Interact with the Endocannabinoid System?

Phytocannabinoids (or exogenous cannabinoids as well) are cannabinoids that are introduced into the body from outside sources, from cannabis, other plants, or synthetic cannabinoids. These compounds regulate our Endocannabinoid System as well, and are partial or full agonists/antagonists just like some of the naturally occurring endocannabinoids that our body already produces. Anandamide is most similar to Delta 9 THC, as both are partial CB1 and CB2 receptor agonists, and both have stimulating properties that can heighten your existing feelings, produce euphoria or feelings of joy, (Anandamide in Sanskrit roughly translates to “Bliss”). Anandamide is said to produce most of the behavioral effects of D9 THC but less intensely. CBD works on the endocannabinoid system not by stimulating CB1 or CB2 receptors like THC, but helps the production of anandamide and other endocannabinoids in the body to help maintain homeostasis. Cannabis is one of the only plants in nature to contain phytocannabinoids at such high concentrations, and that is why this plant can give the wide array of powerful pharmacological effects that it has. 

Endocannabinoid Deficiencies/Disorders?

Endocannabinoid Deficiency and issues with the Endocannabinoid System can be traced to issues such as migraines, fibromyalgia, irritable bowel syndrome, and more. This may help explain a part of cannabis’ therapeutic value, as it can bring cannabinoids into the system to regulate issues that the body is not naturally producing endocannabinoids for. Chronic inflammation and pain is often self-medicated with cannabis, or now prescribed in legal states, and all cannabinoids have the therapeutic potential to help in one way or another based on how they agonize or antagonize our CB receptors. That is not to say that one cannabinoid ratio will work for all patients, but since cannabis is an entire spectrum of different cannabinoids, terpenes, flavonoids, and ratios- there should be an individualized treatment for a wide array of issues. The endocannabinoid system is being studied intently for it’s possible resolution of treatment-resistant conditions, and how the endocannabinoid system plays a part in maintaining homeostasis in our bodies. Other forms of endocannabinoid deficiencies may involve a lack of cannabinoid receptors, or synthesizing incomplete AEA and 2-AG compounds that do not bind to our receptors properly. 

Conclusion

In summary, the endocannabinoid system is responsible for many vital functions for healthy human and animal life. This complex network of receptors and ligands extends to most of the animal kingdom and regulates vital subconscious things like our appetites, mental states, pain perception, even sexual health and more. Figuring out how to properly regulate and maintain homeostasis via the endocannabinoid system for all individuals will be a breakthrough for humanity, though science still to this day is strict due to the illegal status of cannabis. Since hemp and CBD have become legal, however, the natural wellness movement has taken huge strides in cannabis/hemp science and we have really begun to study what these exo and endogenous compounds can do for our daily lives and overall health. We hope to see a future where we have a true marriage between the science of medicine and the science of cannabis and the treatments will be as individual as the patients themselves. When consuming cannabis or hemp products it’s important to remember, it’s not about getting high as that is a short-lived chase, it’s about maintaining balance and being aware of your health.