It is rumored that the endocannabinoid system (ECS) has been around for the last 600 million years. This is because the ECS is present in the earliest forms of life- the sponges which have been around for that long. It is sad that we did not hear about it until the 1960s when Dr Robert Mechoulam began his ground breaking work on exploring cannabinoids and endocannabinoids that form part of the ECS. It is also unfortunate that the ECS has been excluded from medical school syllabus for so many years, but let’s reserve that argument for another day. In this article, we shall be exploring the components of the ECS and why this system is essential for human life.


What Makes Up The Endocannabinoid System?


In the year 1964, an Israeli professor working at the Hebrew University of Jerusalem isolated a molecule in the cannabis plant that caused healing relief to the human body- tetrahydrocannabinol (THC). It was his curiosity about how the cannabis plant works to provide the effects it has on the human body that set off the journey towards the discovery of the ECS.


But the use of cannabis dates back  to ancient civilizations that arose from banks of great rivers such as the Indus River in India, Hwang-Ho in China and river Tigris and Euphrates in Mesopotamia. Before Mechoulam began his research work, herbalists were already tapping into the healing power of cannabis.


Years later, together with other scientists, Mechoulam discovered that the body produced its own cannabinoids that act in a similar way to plant phytocannabinoids. This could also be argued in the reverse; plant cannabinoids emulate the actions and effects of endocannabinoids. We shall look at this endocannabinoids in detail later.


Later in the 1990s another researcher by the name of Lisa A. Matsuda identified the first cannabinod receptor in the brain- the CB1 receptor which binds the endogenous cannabinoids as well as plant cannabinoids such as THC. Later a second receptor was identified and in 1995, the two receptors were classified as the CB1 and CB2 receptors.


With this, the body’s ECS is comprised of three major components:


  • Receptors spread throughout the body
  • Endocannabinoids
  • Metabolic enzymes which break down endocannabinoids

We shall look at these components in detail/


1.   Cannabinoid Receptors


The CB1 receptor was the first to be identified; it is found predominantly in the brain and the central nervous system. It is responsible for modulating higher centre functions and it achieves this by interacting with cannabinoids.  Another receptor was later identified and it was named the CB2 receptor. This receptor is predominantly found in the immune system. It is responsible for modulating immunity and other peripheral functions. It achieves this by interacting with cannabinoids (CBD) as well. The CB2 receptor does not do much in a healthy state. It however kicks in when the body is in a disease state and it sets off immune responses that are both defensive and protective.


Later a third and less commonly discussed receptor was identified; the GPR55 receptor. Not much has been studied about this third receptor.


Phytocannabinoids found in cannabis are able to interact with cannabinoid receptors in their own unique ways. When they do this, they produce effects similar to those produced by endocannabinoids.


2.   Endocannabinoids


These are molecules found in the body that are able to interact with cannabinoid receptors. They are made up of polyunsaturated fatty acids that are derived from arachidonic acid. The primary endocannabinoid molecule is known as anandamide (bliss molecule). The second endocannabinoid is 2-arachidonoylglycerol (2-AG).More endocannabinoids are being investigated and they include: 2-arachidonylglycerol ether and N-arachidonoyldopamine (NADA).


Anandamide binds to both the CB1 and the CB2 receptors to help in supporting the ECS. It is also known as the bliss molecule because it causes extreme happiness once released. However, endocannabinoids are quickly removed from circulation as soon as they have performed their role. This also explains why anandamide, unlike THC cannot cause euphoria. If it was allowed to accumulate in the body, it would probably “make us high” in a similar way to how THC can get one intoxicated.


2-AG also interacts with both the CB1 and the CB2 receptor but with a lower affinity.


3.   Metabolic enzymes


As mentioned earlier, endocannabinoids are removed from the system as soon as they have completed their function. To achieve this, the metabolic enzymes come into play. FAAH is responsible for breaking down anandamide while MAGL is responsible for breaking down 2-AG. This means that endocannabinoids do not accumulate in the body unlike phytocannabinoids. Endocannabinoids are released on a need basis.


Why Endo cannabidoids Are Different From Other Neurotransmitters


Endocannabinods work in a retrograde manner, which is different from how other neurotransmitters work. Brain cells send out chemical messages that are relayed from cell to the next and this controls our feelings thoughts and actions. Most neurotransmitters are released from a cell known as a presynaptic cell and they cross a synapse (gap) to get to post synaptic cells from where they trigger a definite action.


Endocannabinoids work in the opposite manner. They are released from the post synaptic cells, cross the synaptic junction and get to the presynaptic cells where they bind to endocannabinoid receptors. This is what is referred to as retrograde mechanism.


Unlike other neurotransmitters, endocannabinoids are manufactured on demand.


Acting in a retrograde fashion allows endocannabinoids to have control over the release of other neurotransmitters from the presynaptic cells. They work as a “dimmer switch” to regulate the release and functioning of other neurotransmitters.


The ECS And Homeostasis


Homeostasis is balance of the internal environment of the body, all physiological parameters being within limits. This means when the external conditions fluctuate, the internal mechanism adjusts to ensure that the internal environment remains in check. For example when the external temperatures increase the body initiates mechanisms such as sweating so that the body temperature remains moderate. The same applies to hormonal levels, hunger and other important functions in the body.


The ECS is responsible for maintaining homeostasis in the body. Through the endocannabonids interaction with endocannabinoid receptors, the body is able to keep all systems in check. Among the important functions that are regulated by the ECS are:


  • Appetite
  • Pain
  • Immunity
  • Digestion
  • Mood
  • Memory
  • Temperature
  • Sleep
  • Motor control
  • Fertility


The ECS works in a direct, targeted and purposeful manner. For example, when your body temperature is in the extreme range the ECS kicks in to correct that without influencing other systems. Once the endocannabinoids working through the ECS have managed to restore optimal temperatures they are quickly broken down by metabolic enzymes and removed from the system. Should they be left to persist in the body, they may cause an upset in the opposite direction of what they had just restored. This is what makes this system unique.


Phytocananbinoids on the other hand work in a different way. Because they are not taken out of the body immediately they may end up causing side effects such as euphoria and paranoia among others.


It is important that the ECS functions optimally at all times, when there is a failure in the ECS the resulting state can be classified as an endocannabinoid deficiency.


Chroni Endocannabinoid Deficiency (CECD)


When the endocannabinoid system is in disarray the body is likely to develop any of the conditions under the CECD umbrella. All these conditions are interrelated and linked to a malfunctioning ECS. The common conditions in this bracket include:


  • Fibromyalgia
  • Migraine
  • Irritable bowel syndrome


Most of these conditions have been difficult to treat in the past. Traditional treatment has often focused on managing symptoms as opposed to finding a cure. More studies on the ECS could provide a breakthrough in the treatment of these chronic conditions.


Why Does the ECS Intrigue Us


Many things about the ECS are intriguing. For starters, it is perplexing how such an important system went unnoticed by scientists for so many years. Also, learning about the potential of this system to influence both basic functions as well as complex disease processes is interesting. Lastly, it is fascinating that such a “controversial” plant such as cannabis could have so much potential to influence such a vital system as the ECS.