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Understanding the Endocannabinoid System

The endocannabinoid system has an important role to play in the body that goes well beyond what the name suggests. It is a complex, cell-signaling system in the body that was identified well in the early 1990s by a researching team who were exploring THC, which is a well-known cannabinoid or marijuana. Cannabinoids are common compounds that are found in cannabis. The medical community is still trying to understand how the endocannabinoid system works and what role it plays in the regulation of various functions in the body. We take a closer look at understanding the endocannabinoid system of the body.

What is the Endocannabinoid System?

What is the Endocannabinoid System?

The endocannabinoid system (ECS) plays a crucial role in regulating several functions and processes in the body. Endocannabinoid system (ECS) is a cell-signaling system that is suspected of playing a role in regulating a wide range of processes and functions in the body, such as:

  • Mood
  • Appetite
  • Sleep
  • Memory
  • Fertility and reproduction

The reason why it is said that endocannabinoid system (ECS) is suspected of playing a role in these functions is that the medical community is still trying to fully understand the endocannabinoid system.(1)

The endocannabinoid system (ECS) was identified by researchers in the early 1990s while exploring THC, which is a well-known cannabinoid, which is compounds that are found in cannabis, or marijuana.

Endocannabinoid stands for cannabis and endogenous, meaning cannabis-like substances that are produced naturally inside of the body.

How Does The Endocannabinoid System Function?

The endocannabinoid system (ECS) is made up of three primary components. These include:

  • Endocannabinoids
  • Enzymes that help in the breaking down of cannabinoids and endocannabinoids
  • Receptors that are present in the nervous system and around the body that cannabinoids and endocannabinoids bond with
  • Endocannabinoids

Also known as endogenous cannabinoids, endocannabinoids are molecules that are manufactured by the body. They are similar to cannabinoids but differ in that they are manufactured by the body naturally. Experts have so far identified two significant endocannabinoids. These include:

  • 2-arachidonoylglyerol (2-AG)
  • anandamide (AEA)

These two endocannabinoids are responsible for keeping the internal functions running properly, and they are produced by the body as they are needed. This makes it challenging to determine what the average levels for each should be.(2)

  • Enzyme
  • These enzymes are responsible for breaking down the endocannabinoids after they have carried out their role. There are two major enzymes that help carry this out:
    Monoacylglycerol acid lipase that is broken down into 2-AG
  • Fatty acid amide hydrolase, which is broken down into AEA
  • Endocannabinoid Receptors

Endocannabinoid receptors can be found throughout your body, and the endocannabinoids bind to these receptors in order to signal that it is time for the endocannabinoid system (ECS) to take action. There are only two major endocannabinoid receptors.(3) These are:

  • CB1 receptors that are found commonly in the central nervous system(4)
  • CB2 receptors that are found commonly in the peripheral nervous system, especially in the immune cells(5)
  • Endocannabinoids are known to bind to either of these receptors, and the resulting effects depend on the location where the receptor is based and which endocannabinoid is binding to the receptor.

For instance, the endocannabinoids may target the CB1 receptors present in a spinal nerve to relieve pain. Others can bind to a CB2 receptor that is present in your immune cells for signaling that your body is experiencing inflammation, which is a common symptom of autoimmune disorders.

What Role Does The Endocannabinoid System Play?

The endocannabinoid system (ECS) is a complicated one, and researchers still have not been able to determine precisely how the system works or what all are the functions associated with the ECS system. Nevertheless, research has shown that the endocannabinoid system is linked to the following processes and functions(6):

  • Metabolism
  • Chronic pain
  • Appetite and digestion
  • Mood
  • Motor control
  • Inflammation and other immune system responses
  • Sleep
  • Learning and memory
  • Muscle formation
  • Cardiovascular system function
  • Liver function
  • Bone growth and remodeling
  • Stress
  • Nerve and skin function
  • Reproductive system function

All these various functions are believed to contribute to homeostasis, which is a condition that refers to the stability of the body’s internal environment. For instance, if an outside force, including pain from a wound or injury or a fever, throws off the body’s homeostasis, your endocannabinoid system will step in to help your body return back to its normal and ideal condition and operation.

Today, scientists believe that the primary role of the endocannabinoid system is to maintain a condition of homeostasis in the body.

What Is The Role of THC In All This?

THC (tetrahydrocannabinol) is one of the major cannabinoids that is found in cannabis. This is the compound present in cannabis that works to get you ‘high.’ Once THC goes into your body, it starts to interact with the endocannabinoid system by binding to receptors, just like the endocannabinoid receptors do. It is also especially powerful because it can bind to both the CB1 and CB2 receptors.

This allows THC to have a wide range of effects on your mind and whole body, though some outcomes are more desirable than others. For instance, THC is known to decrease the level of pain and also stimulate your appetite as well. However, at the same time, it is also known to cause anxiety and paranoia in some people.

Even till date experts are still looking into methods of producing synthetic THC cannabinoids that can interact with the endocannabinoid system in only positive ways.

What Is The Role of CBD In All This?

Similar to THC, CBD (cannabidiol) is the other major cannabinoid that is also found in cannabis. However, unlike THC, CBD does not work to make you experience a ‘high’ and also does not typically cause any adverse side effects.

While experts are not entirely sure as to exactly how CBD interacts with the endocannabinoid system (ECS), but it is known that CBD does not bind with the CB1 and CB2 receptors in the manner in which THC binds.

Instead of this, some researchers believe that CBD works by preventing the endocannabinoids from being broken down and this allows them to a more significant effect on your body. Others also believe that CBD binds with a receptor that is yet to be discovered.

While the exact details of how CBD works are still unclear and under debate, research has nevertheless, shown that CBD can help you deal with nausea, pain, and other symptoms that are associated with many diseases and disorders.

What is Clinical Endocannabinoid Deficiency (CECD)?

According to some medical experts, there is a theory that is known as clinical endocannabinoid deficiency or CECD. This theory revolves around the fact that low levels of endocannabinoid levels in the body or dysfunction of the endocannabinoid system (ECS) can cause many other conditions to develop.(7)

In 2016, there was an article published that reviewed over ten years of research that has been done on this subject. This article suggested that the theory could explain why some people end up developing fibromyalgia, irritable bowel syndrome, and migraine, without any underlying cause.(8)

These conditions are known as functional conditions or even as central sensitivity syndromes. They are usually resistant to most treatments, and researchers are looking to see if cannabis-based treatments can work for these conditions. These conditions are also known to typically involve more than one body system. For example, the condition of fibromyalgia involves both the central and peripheral nervous system, the endocrine system, the immune system, and also the digestive system. Fibromyalgia is also known to be linked with premature perimenopause, early hysterectomy, as well as fertility challenges.

There is no underlying cause behind these conditions, and these conditions are usually also resistant to treatment and may also occur alongside each other in some people. It is likely that if CECD has a role to play in any of these conditions, then targeting the endocannabinoid production or the endocannabinoid system could potentially be the missing key to treatment. Still a lot more research is needed to conclusively prove this connection.


The endocannabinoid system is known to play a big role in maintaining the body’s internal processes stable. However, there is not much known about the ECS system, and more research is still needed to understand the exact process. As researchers and experts from all fields work towards developing a better understanding of the endocannabinoid system (ECS), it is likely to hold the key to the treatment of various conditions.


  1. Mechoulam, R. and Parker, L.A., 2013. The endocannabinoid system and the brain. Annual review of psychology, 64, pp.21-47.
  2. Mechoulam, R., Fride, E. and Di Marzo, V., 1998. Endocannabinoids. European journal of pharmacology, 359(1), pp.1-18.
  3. Pacher, P., Bátkai, S. and Kunos, G., 2006. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacological reviews, 58(3), pp.389-462.
  4. Marsicano, G., Goodenough, S., Monory, K., Hermann, H., Eder, M., Cannich, A., Azad, S.C., Cascio, M.G., Gutiérrez, S.O., van der Stelt, M. and López-Rodríguez, M.L., 2003. CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science, 302(5642), pp.84-88.
  5. Pertwee, R.G., 1997. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacology & therapeutics, 74(2), pp.129-180.
  6. Zou, S. and Kumar, U., 2018. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. International journal of molecular sciences, 19(3), p.833.
  7. Russo, E.B., 2008. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?. Neuro endocrinology letters, 29(2), pp.192-200.
  8. Russo, E.B., 2016. Clinical endocannabinoid deficiency reconsidered: current research supports the theory in migraine, fibromyalgia, irritable bowel, and other treatment-resistant syndromes. Cannabis and cannabinoid research, 1(1), pp.154-165.
Pramod Kerkar, M.D., FFARCSI, DA
Pramod Kerkar, M.D., FFARCSI, DA
Written, Edited or Reviewed By: Pramod Kerkar, M.D., FFARCSI, DA Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:August 2, 2021

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