Endocannabinoid System – Complete Overview

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One of the most profound findings that were made in the 1980s is that our bodies have a system of receptors, enzymes and endocannabinoids called the endogenous cannabinoid system (ECS or Endocannabinoid System). This articles explores and explains the system and how it interacts with our bodies and marijuana.

Cannabis is only one herb yet it comes with a variety of compounds that seem to interact in numerous aspects of both our bodies and minds. Besides getting you high, the same plant has been reported to help treat symptoms related to cancer, multiple sclerosis, glaucoma, Parkinson’s disease, insomnia. So, how is this even possible, considering that all these examples of illnesses have vastly different causes, symptoms, and physiological states?

Without a doubt, this is only heard of when talking about cure-all remedies that show up only as expensive fads, promising a lot of results but with no scientific backing or clinical evidence. Any wary person would walk away skeptical. However, with cannabis, there is an explosion of proof, especially in the last quarter century, and the results have been getting interesting by the day.

What is the Endocannabinoid System?

The ECS is a collection of endocannabinoids and the receptors which control important physiological processes in the human body. The receptors and endocannabinoids are distributed throughout the body including the brain, spine, organs, glands, immune cells and in connective tissues. Depending on the tissue, this system has been shown to perform different tasks, but the objective is always homeostasis.

In biological terms, homeostasis is the regulation of the internal environment even in a changing external environment. This process helps body cells maintain pH, temperature and other factors crucial for optimum body performance. Cannabinoids are compounds that can activate receptors in this system and they have been shown to support homeostasis at almost all levels of biological life.

For instance, cannabinoids allow different organs and cell types to communicate since they are present at the intersection of the numerous systems in our bodies. When an injury occurs, therefore, cannabinoids will be present at the site doing various tasks such as:

Reducing the release of sensitizers and activators from the damaged tissue

Calming the immune cells around the site to prevent over-production of pro-inflammatory compounds

Stabilizing the nerve cells to prevent excess firing and hence mitigating sensations of pain.

This shows the multi-pronged effects of the ECS system on different cell types, in this case for the single purpose of minimizing damage and reducing pain. Therefore, it is crucial to understand how this system works since clearly, it has a lot of potential on how we can improve both our mental and physical well-being.

The Main Components of the Endocannabinoid System (ECS)

Scientists now believe that the endocannabinoid system evolved more than 600 million years ago in primitive animals since it can be found in all vertebrate species as well as nematodes and sea squirts. ECS is composed of three main parts namely;

  • Cannabinoid receptors
  • Endocannabinoids
  • Enzymes

Cannabinoid Receptors

Cannabinoid receptors are present everywhere in the body embedded on the surfaces of cells and are believed to be more than any other receptors in the body. When they are activated, they transmit the new information to the inside of the cell hence triggering the appropriate cellular response. Currently, researchers have been able to single out two main receptors in the ECS: CB1 and CB2 receptors.

CB1 Receptors

CB1 receptors are mostly found in the areas they influence such as connective tissues, nervous system, testicles, glands, and organs. For instance, there is a high concentration of CB1 receptors in the hypothalamus and amygdala regions of the brain which are responsible for appetite regulation and memory respectively. CB1 receptors interact with THC to manifest psychoactive effects. They are also concentrated on nerve endings where they are believed to reduce the sensation of pain.

CB2 Receptors

CB2 receptors are predominant predominantly found in the immune system. CB2 receptors work to reduce inflammation when activated. Inflammation is a common immune response which is a symptom of many conditions and illnesses. THC found in cannabis is also able to bind to CB2 receptors and activate them just like endocannabinoids produced in the body.

The other active compound in cannabis, CBD does not bind directly to receptors but rather works by inhibiting an enzyme known as FAAH. FAAH is responsible for breaking down anandamide, a crucial endocannabinoid in the body. When FAAH is inhibited, the rate of breaking down anandamide reduces which leads to its build-up in the brain.

However, many tissues contain both CB1 and CB2 receptors each associated with a different mechanism of action. Scientists think there could be more receptors in the system awaiting discovery.


Endocannabinoids are molecules produced naturally in the body to activate cannabinoid receptors when the need arises just like THC. The prefix “endo” means that these substances are naturally produced in the body as opposed to those can be found in plants such as THC and CBD (phytocannabinoids) or those that are synthetically produced.

Anandamide and 2-AG are some of the most studied endocannabinoids which were discovered in 1992 and 1995 respectively. 2AG is predominant in the brain while anandamide is mostly found in the rest of the body. Both cannabinoids, however, can bind to both CB1 and CB2 receptors with varying effects.

Endocannabinoids are short-term neurotransmitters, which means they are only released when needed and their presence is temporary. After release, they are quickly broken down by enzymes such as FAAH (fatty acid amide hydrolase) and MAGL (monoacylglycerol lipase). In contrast, other molecular signals in the body such as hormones or normal neurotransmitters can linger for seconds, minutes or even be packaged for later use. Cannabinoids from outside the body such as THC, CBD, and CBN found in cannabis stick around for long after consumption which activates the ECS more strongly and for longer than usual endocannabinoids.

Functions of the Endocannabinoid System

As already shown, the endocannabinoid system interacts with numerous types of cells across the body with the ability to make each cell type respond differently after activation.  As a result, it has a huge variety of roles that it plays in our bodies including the regulation of sleep, mood, appetite, memory, pain, immune function, inflammation, metabolism, reproduction, digestion, neuroprotection, and development.

Studies now show that patients with conditions such as Parkinson’s disease, chronic pain, arthritis, and cancer have a higher concentration of endocannabinoids which further supports the hunch that the ECS is nature’s way of maintaining homeostasis.


Besides its 5,000-year history of therapeutic use as well as an average of two publications on a daily basis in the last two decades concerning marijuana, most doctors still do not understand the workings of the endocannabinoid system and the potential benefits of cannabis which interacts heavily with this system.

This means that there is currently a huge gap in terms of indication, dosage, and route of administration of medical cannabis which has led to most patients self-medicating. Organizations such as the American Medical Association and American College of Physicians as well as the public have been pushing for more research on the subject which holds a lot of promise in terms of medicine. Unlike synthetic derivatives, natural cannabis contains over a hundred different cannabinoids besides THC that work synergistically to provide some of the proven therapeutic benefits and reduce side effects.

The fact that there is a whole 600-year-old system that produces endocannabinoids and is specifically evolved to only accept these types of molecules is already proof enough that cannabis has some medicinal value and even more potential. As we continue to learn more about this new science of cannabis, cannabinoids and the receptors, one thing remains crystal clear: we need a properly working endocannabinoid system to maintain good health in a quickly changing and hostile external environment.

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