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The Endocannabinoid System (ECS)

The Endocannabinoid System (ECS)

In the year 2009, Nick DiPatrizio, a neuropharmacologist made yet another discovery about the astonishing endocannabinoid system. While conducting studies on lab mice he discovered that “hunger, and the taste of fat leads to increased endocannabinoid levels in the jejunum of mice.” This meant that endocannabinoid signaling in the small intestines was prompting the desire to eat.

Appetite is just one of the physiologic functions in the body that are influenced by the endocannabinoid system. It is surprising to know that two decades back, very little was known or said about such a profound body system. Dr Raphael Mechoulam, a professor at the Hebrew University of Jerusalem, is credited with beginning the work of exploring the ECS.

What is the endocannabinoid system?

In a nutshell, this is a system in the body of mammals that is tasked with the responsibility of maintaining homeostasis. Homeostasis is defined by the Council of Europe Guidelines on the quality, safety and marketing of food supplements (2005) as “The status of a person whose physiological parameters function within the limits considered as normal.”

To get a better grasp of this diverse system and how it maintains physiologic balance, we must first understand how our bodies function. Our bodies, and those of other mammals, receive information from the outside world through stimuli, process the information and give an appropriate response to it. This calls for communication between different cells so that the information can be relayed and responded to appropriately.

This communication allows our bodies to meet certain vital needs such as feeding, temperature regulation, reproduction, and so much more. The different cells in our bodies make up tissues and the tissues make up organs of the body. Cells that perform similar functions are grouped together to form systems. You might be familiar with the digestive system that runs all the way from your mouth to your anal opening and the respiratory system which comprises of the nasal canals, air passages and the lungs.

The ECS is another of these essential systems that has been unfortunately excluded from medical textbooks for many years. It is indeed disturbing to comprehend how it remained undiscovered for so long, while science currently acknowledges that 55% of the total body’s receptors are endocannabinoid receptors. Then it is intriguing to imagine what science will reveal to us about our bodies in the next decade or so.

What makes up The ECS

The ECS is an internal signaling system comprising of endocannabinoids, cannabinoid receptors and metabolic enzymes.

It is present in all mammals.

How the ECS works

This system centers on the interaction of cannabinoids and endocannabinoid receptors. Metabolic enzymes come into play when the endocannabinoids have completed their role and need to be removed from circulation.

The cannabinoids receptors are cell membrane proteins that are produced by body cells to provide a surface for endocannabinoids to bind to. The mechanism of interaction is a key and lock mechanism, where the cannabinoids fit into the structure of the receptor like a key fitting into a lock. When this happens, there is activation of a physiological process that is geared towards maintaining homeostasis in the body.

The ECS regulates different functions in the body including  regulation of food intake,  endocrine functions, motor functions, cognitive functions and vision among others.

Cannabinoids receptors

So far, two main cannabinoid receptors have been identified: the CB1 and the CB2 receptors. A third receptor known as orphan receptor GPR55 is being investigated.

Lisa A.Matsuda has been credited with identifying and describing the CB1 receptor in the 1990s. The CB1 receptor has been found predominantly in the central nervous system and consequently it has been shown to modulate CNS related functions such as the feeling of extreme happiness. The CB2 receptor was later indentified and found to be predominant in the peripheral tissues. With this system of receptors spread out through the body, the endocannabinoid system is able to influence most functions of body.


Endocannabinoids are polyunsaturated fatty acids derived from arachidonic acid. There are two main endocannabinoids that have been identified in the human body, one is Anandamide which is also called the bliss molecule while the other 2-AG.

These endocannabinoids are synthesized in the cell membranes of the stimulated calls from where they cross the synaptic cleft to bind onto receptors on pre synaptic cells. If you understand how normal signaling works, you will have sensed that this is a retrograde signaling system. In a normal signaling pathway, the neurotransmitter is released from the pre synaptic cell and it crosses over the synaptic cleft to stimulate the post synaptic cell.

Medical jargon aside, the signaling system occurring in the ECS works in a backwards fashion so that the endocannabinoids can bind to receptors on pre synaptic cells to inhibit the release of neurotransmitters such as Dopamine, GABA and Glutamate.

Endocannabinoids are broken down and taken out of the system as soon as they have completed their role. They do not linger in the body, and this partly explains why your body’s own endocannabinoids do not make you "high" by binding to the CB1 receptor, while plant derived phytocannabinoids such as THC make you "high". Anandamide is broken down by the metabolic enzyme FAAH while 2-AG is broken down by MAGL.

Roles of the Endocannabinoids System

The main role of the ECS is to promote homeostasis in the body. It is able to achieve this by interacting with different neurotransmitters in the body such as: GABA, glutamate, acetylcholine, norepinephrine, histamine, serotonin and others through endocannabinoids and endocannabinoid receptors.

CBD and the Endocannabinoid System

Science has proven that plant derived cannabinoids and terpenes are able to interact with endocannabinoid receptors. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are among the most studied cannabinoids found in cannabis. THC binds to the CB1 receptor in a similar way that anandamide does. CBD on the other hand has a weak affinity for both CB1 and CB2 receptors, but it is able to support homeostasis through indirect interaction with the CB2 receptor. Both THC and CBD support maintain and optimize the functions of a healthy ECS.

Given that CBD does not make you "high", it has now been legalized as a supplement throughout the UK and many other countries worldwide, and many people are now enjoying the benefits of CBD.

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