THE ENDOCANNABINOID SYSTEM

Cannabis has a long history of being used for its therapeutic potential dating as far back as 2800BC, Throughout history, many different cultures have used Cannabis to treat a wide variety of ailments, including menstrual symptoms, pain, epilepsy, nausea and much more. However, it wasn’t until recently that we have begun to really study and understand the science behind how cannabis interacts with our bodies to have these potential benefits. This new found understanding is largely due to the discovery of the Endocannabinoid system (ECS).

“The endogenous cannabinoid system—named for the plant that led to its discovery—is one of the most important physiologic systems involved in establishing and maintaining human health. Endocannabinoids and their receptors are found throughout the body: in the brain, organs, connective tissues, glands, and immune cells. With its complex actions in our immune system, nervous system, and virtually all of the body’s organs, the endocannabinoids are literally a bridge between body and mind. By understanding this system, we begin to see a mechanism that could connect brain activity and states of physical health and disease.”-Bradley E. Alger, Ph.D.

What is the Endocannabinoid System?

The Endocannabinoid System is a signalling system that was discovered in the early 1990’s by a Czech analytical chemist named Lumír Hanuš and an American pharmacologist named William Devane. Since its discovery, there has been an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Today, the ECS has emerged as a central component in many aspects of human health and there is a substantial amount of evidence that it’s dysregulation contributes to many health issues, including psychiatric disorders, pain and inflammation. This is why, when it comes to understanding the potential therapeutic benefits of CBD and other cannabinoids, understanding the ECS is essential. 

The Endocannabinoid System comprises three components: Endocannabinoids, the receptors for those endocannabinoids and the enzymes that are responsible for their synthesis or degradation.

What are Cannabinoid Receptors?

Cannabinoid receptors are G protein-coupled receptors that mediate almost all effects of phytocannabinoids from the cannabis plant, such as THC and CBD, and the cannabinoids produced by the body called endocannabinoids (discussed later). The most widely prevalent and studied cannabinoid receptors are the CB1 and CB2 receptors. The locations of these receptors throughout the body strongly suggests that they play important roles in regulating the functions of many important organs and tissue.

 CB1 is highly present in the central nervous system (CNS) which contains major brain regions that mediate a wide variety of high-order behavioral functions, including learning and memory, decision making, sensory and motor responsiveness, emotional reactions and other homeostatic processes. It is also present at lower levels in a variety of Peripheral Nervous system (PNS) and in some peripheral tissues as well. 

CB2 is mostly found in immune cells and are expressed at much lower levels in the CNS compared to CB1. It can be also found in other peripheral tissues, including the cardiovascular system, GI tract, liver and reproductive system. CB2 receptors have been the subject of considerable attention, primarily due to their promising therapeutic potential for treating various pathologies while avoiding the adverse psychotropic effects that can accompany CB1 receptor-based therapies.

Although CB1 and CB2 are considered to be the primary cannabinoid receptors,  There is increasing data that has prompted some researchers to consider TRP channels to be “ionotropic cannabinoid receptors”  making them also potential targets for therapeutic uses such as pain treatments. 

Transient receptor potential (TRP) channels are a group of membrane proteins involved in the mediation of a variety of processes that translate external stimuli into sensation of temperature, smell, taste, vision, and pain perception. So far, there have been six TRP channels reported to be activated by cannabinoids: TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and TRPM8. Research has shown that “many diseases involve TRP channel dysfunction, including neuropathic pain, inflammation, and respiratory disorders.”

What are Endocannabinoids?

Endocannabinoids are naturally occurring compounds that interact with and stimulate the activity of cannabinoid receptors, thereby initiating a physiological response. These cannabinoids differ from classic neurotransmitters because they are produced on demand as opposed to being produced ahead of time and stored. Although several have been identified,  anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) have emerged as the most relevant and prevalent. 

AEA is only a partial activator of CB1 and is almost inactive at CB2. However it has been shown to fully activate TRPV1 which is best known for its significant role in synaptic transmission and pain regulation. There is also some information that AEA helps to negatively regulate 2-AG biosynthesis and physiological effects in parts of the brain, which suggests that it plays a significant role in synaptic transmission.

 2-AG acts as a full agonist at both cannabinoid receptors and research has shown that at its floor level, it is approximately 1000 times more prevalent than AEA in the brain. In light of these facts, 2-AG is considered the primary endocannabinoid for cannabinoid receptors in the central nervous system.

What are ECS Enzymes?

Enzymes synthesis Endocannabinoids but they also serve the very important role of breaking them down once they have served their function. The enzymes that break down endocannabinoids are of particular interest when it comes to the function of the ECS. 

Fatty Acid Amide Hydrolase (FAAH) is responsible for breaking down the AEA endocannabinoid

Monoacylglycerol acid lipase (MGL) typically breaks down 2-AG.

How can the ECS be used therapeutically?

The discovery of the ECS in the 90’s triggered a huge accumulation of studies exploring its regulatory functions in health and disease. This resulted in the conclusion that modulating the activity of the endocannabinoid system holds therapeutic potential in a wide range of diseases and conditions, ranging from mood and anxiety disorders to pain, obesity, PTSD and more. 

Scientists believe that by activating or deactivating the cannabinoid receptors or stimulating or inhibiting endocannabinoids or enzymes, they might be able to modulate the ECS’s regulatory functions and therefore manipulate the physiological response associated with it. For example, studies have shown that increasing the level of AEA or 2-AG in the body has an anti-anxiety like effect in stressful situations. One way this has been achieved is through inhibiting the enzymes from breaking them down. Some have also raised the possibility of developing a medicine that selectively activates cannabinoid receptors located outside the blood-brain barrier to induce pain relief, improve certain intestinal and cardiovascular disorders, and inhibit the proliferation and spread of cancers while also avoiding the psychoactive effects activating CB1 receptors in the brain. 

How does CBD affect the endocannabinoid system?

Phytocannabinoids are cannabinoids just like the endocannabinoids produced in the ECS. The major difference being that phytocannabinoids are the naturally occurring molecules in Cannabis rather than the body. There are over 100 cannabinoids in cannabis. However, the most prevalent and well known phytocannabinoids are THC and CBD. When injusted, these compounds can mimic the action of endocannabinoids. As a result of THC being intoxicating and possibly habit forming, many pharmacologists have avoided studying it for therapeutic purposes. However, CBD is not intoxicating and has, therefore, been the focus of a lot of attention for its potential health benefits.

Among all of the phytocannabinoids found in cannabis, CBD is thought to have  the highest potential for therapeutic use. Most studies have concluded that CBD has little to no direct effect on the CB1 and CB2 receptors. Instead, CBD likely exerts an indirect effect by targeting molecules that do have a direct effect on the receptors. For example, one way CBD is thought to affect the ECS is as a  “negative allosteric modulator” of CB1 receptors. This means that it weakens the effects of other cannabinoids that would normally activate the CB1 receptor, such as THC or 2-AG. This gives CBD the potential to help treat CNS and peripheral disorders, such as anxiety, depression and chronic pain, while avoiding the adverse effects associated with activating the CB1 receptors. 

Another way CBD is thought to possibly affect the ECS is by inhibiting the degradation of circulating endocannabinoids. Studies have shown CBD might do this with anandamide by inhibiting the protein that carries it to the FAAH enzyme to be broken down. The increase in anandamide has a variety of therapeutic implications. One study even suggests that the inhibition of the deactivation of anandamide may contribute to the antipsychotic effects of CBD, indicating potential in the treatment of schizophrenia.

Although the exact mode of action by which CBD affects the ECS is not completely understood, it seems to interact with an array of molecular targets, which allows its potential use in a wide range of pathological conditions. In fact, CBD is thought to target up to 65 different molecular targets both within and outside of the ECS. In turn, CBD is being investigated as a potential therapeutic tool in treating things such as addiction, obesity, inflammation, central nervous system disorders, and much more.

Here are some CBD products that we like to use:

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