The Endocannabinoid System

The Endocannabinoid System: An Overview

The endocannabinoid system (commonly known as the ECS) has been named after the plant, which led to its discovery. It is arguably among the most important body systems that help establish and maintain human health. You will find endocannabinoids along with their receptors all over the body.

They are present in the brain, immune cells, organs, glands, and connective tissues. This system will perform a different task in every tissue even though the goal is shared, homeostasis. This is the maintenance of some stable internal environment even though there are fluctuations in the external environment.

You will also find cannabinoids and endocannabinoids at the intersection of different body systems. This allows for coordination and communication between various types of cells. For instance, at an injury site, you will find cannabinoids decreasing the rate at which sensitizers and activators are released. They stabilize the nerve cell and prevent excess firing as well as calm the nearby immune cells.

The endocannabinoid has complex actions in the immune system, body organs, and nervous system. It is, therefore, a bridge between our body and the mind. When we understand the system, we can see the mechanism explaining how consciousness promotes disease or health. Without any further ado, let us get started.

How Does It Work?

Now that you know what the endocannabinoid system is, the next thing that you will want to know is how the ECS works. Essentially, the endocannabinoid system comprises three main components.

These are the endocannabinoids, enzymes, and receptors. In understanding how the ECS works, we shall have a look at these three core components:

  • Endocannabinoids- These are also known as endogenous cannabinoids and are simply molecules made by the body. They are similar to cannabinoids, only that the body itself produces them. So far, experts have managed to identify two main types of endocannabinoids, namely anandamide (AEA) and 2-arachidonoylglyerol (2-AG). These are responsible for keeping the internal functions just running smoothly. The body produces them just as needed, which makes it hard to understand the typical levels of each of them.
  • Endocannabinoid receptors- You will find these receptors all over the body. Endocannabinoids will bind to them to signal that the endocannabinoid system should take action. The two typical endocannabinoid receptors are CB1 and CB2 receptors. You will find CB1 receptors mostly in your central nervous system. CB2 receptors, on the other hand, are typical in the peripheral nervous system, particularly the immune cells. You need to understand that endocannabinoids can bind to either of these receptors. The effects will depend on the location of the receptors and the endocannabinoid that is bind to. For instance, endocannabinoids can bind to CB2 receptors in the immune cells to send signals that the body is experiencing inflammation.
  • Enzymes- The role of enzymes is breaking down the endocannabinoids after they have carried out their functions. There exist two main enzymes that are responsible for that. The first enzyme is fatty acid amide hydrolase that breaks AEA. On the other hand, monoacylglycerol acid lipase breaks down the 2-AG.

The Endocannabinoid System Structure And Function

Endocannabinoid system

How is it possible to remain at homeostasis with the complex cell signals, outside influences, and genetic mutations? The solution to that lies in the endocannabinoid system. This system is present almost everywhere in the human body and functions in the maintenance of homeostasis of the human body. It achieves that via a negative feedback loop that activates postsynaptic neurons synthesizing and releasing endocannabinoids to target CB receptors.

Given that CB receptors are generally G-protein-enabled receptors, they can influence the coming signals. As opposed to other cells, that functions as some override signal. You need to note that other cells have signal modifiers that do everything from amplification to diverging. In this case, the neuron overrides those cells.

A practical example is when you have some fracture in the toe which could result in cell death. The following lymphatic response increases blood flow and migration of the white blood cells for the surrounding area. In turn, the endocannabinoid system recognizes the increased lymphatic signals and decides that there is no more need for increased inflammation.

CBD receptors surrounding the immune tissues and cells start binding with cannabinoids. This, in turn, begins to reduce the inflammatory responses gradually. In the brain, a similar process will happen. The stimulation and binding of the CB1 receptors regulate the GABA neurotransmitters. This reduces the pain signals in your brain. As you are already aware, there are two types of receptors in the ECS: the CB1 and CB2 receptors.

In the brain cells, you will primarily find the CB1 receptors. They are densely populated in the immune system, PNS, and the CNS.

On the other hand, you will primarily find CB2 receptors in the immunes system, the CNS, PNS, and the white blood cells. In addition to that, the presence of CB3 receptors has been hypothesized. These are receptors with a particular specialization, even though they are found in several locations all over the human body.


Research shows that cannabis has two very prevalent Phyto-cannabinoids targeting every CB receptor. THC is the active cannabinoid in cannabis that primarily focuses on the CB1 receptor. On the other hand, a terpene called β-caryophyllene selectively targets CB2 receptors.

The Phyto-cannabinoids work by simply mimicking the way endocannabinoids work. It is a bit hard to evaluate the amount of each of these receptors stimulated as well as the amount of Phyto-cannabinoids entering into the bloodstream. Given that cannabis plants essentially function as mass stimuli for the ECS, your body recognizes the phytocannabinoids as simply endocannabinoids.

Lipid Metabolism

The endocannabinoid system runs through the adipose tissue and demonstrates its responsibility in adipogenesis, glucose uptake, and lipogenesis. CB1 receptors stimulate all these. What makes cannabinoids unique is that they get synthesized rapidly and are soon broken after being used.

In this case, there are fewer side effects in the long term. Two common enzymes are responsible for breaking down the endocannabinoids, which are FAAH and MAGL. The ECS is very ubiquitous because cannabinoids are synthesized and degraded rapidly.

As we have just mentioned, the ubiquitous nature of the ECS, the effects of having the level of cannabinoids altered constantly for a while remains unknown. All that is known is that the preferred enzyme for breaking anandamide is FAAH. On the other hand, MAGL is ideal for the degradation of 2-AG.

You also need to know that the inhibitors of these two enzymes have shown success in the stimulation of the ECS. It is likely that by the inhibition of one of both enzymes, levels of different neurotransmitters are adjusted. It is brought at some steady state for an extended period of time. This is achieved when you prevent the hydrolysis of particular Phyto/endocannabinoids responsible for stimulating the release of different neurotransmitters.

How Does THC Interact With ECS?

THC is among the main cannabinoids that you will find in cannabis plants. Suppose you do not know what it is. In that case, THC is the compound that is responsible for the ‘high.’ Once it gets into your body, THC will interact with the endocannabinoid system by simply binding to the receptors just as endocannabinoids do. The reason why THC is potent is partly that it can bind to both receptors (CB1 and CB2).

It is for this reason why it has a wide range of effects on the mind and body. Some effects are more desirable as compared to others. For instance, THC is attributed to help with pain reduction and appetite stimulation. On the flip side, it causes anxiety and paranoia in some instances. Experts are currently looking into producing synthetic THC cannabinoids to interact with the endocannabinoid system in beneficial ways alone.

How Does CBD Interact With the ECS?

As you know, the other prominent cannabinoid found in cannabinoid plants is cannabidiol, also known as CBD. As opposed to its counterpart, THC, CBD does not have psychoactive effects and will therefore not cause a ‘high.’ Having said that, what is the relationship between the endocannabinoid system and CBD? Well, experts are yet to comprehend how CBD interacts with your ECS. All the same, they are aware that it never binds to receptors as THC does.

It is believed that CBD has a role in preventing the endocannabinoids from getting broken down. It is for that reason why they will have more of some effects on the body. Other people believe that CBD does bind to a receptor that is yet to be discovered. Even though the details of how CBD works, it is believed that CBD helps with pain and nausea.

ECS And Mental Health

The ECS has been left unexplored in terms of its hand in mental health. Manipulating the ECS could be highly beneficial in treating schizophrenic patients. Studies conducted among schizophrenic patients show that their anandamide levels are high among acute schizophrenia patients. Anandamide is among the most common endocannabinoid and has a vital role in the human body.

Its level indicates the understanding of the ECS dysfunction since it is related to mental illness. One can easily conclude that the severity of mental illness depends on the dysfunction level of the ECS. Common mental illnesses have overlapping symptoms.

Their difference, therefore, will not be how one feels but the feeling intensity. Some symptoms can intensify owing to the negative or positive feedback loops due to imbalances in different neurotransmitters. Different mental illnesses can be interconnected in a network that is maintained via neurotransmitter function.

When neurotransmitter function is tested and observed, one could get coordinates of where the network issues are occurring. Errors in your ECS could influence mental illnesses since there might be miscommunication between the ECS and the neurotransmitters.

Therefore, it means that targeting the ECS could be more effective than addressing neurotransmitters alone. It is important to treat underlying homeostatic issues via the ECS to restore neurotransmitter function.

What About Endocannabinoid Deficiency?

There are experts with a strong belief in the CECD (clinical endocannabinoid deficiency) theory. It is a theory suggesting that low levels of endocannabinoids in the body or simply ECS dysfunction contributes to the development of particular conditions.

According to an article published in 2016, more than ten years of research suggested that the theory could easily explain why people develop certain conditions. These include migraines and fibromyalgia. The reason for that is that none of the conditions had underlying causes.

Additionally, they are commonly resistant to treatment. If this theory has a hand in such conditions, focusing on the ECS could be the missing link to treatment. All the same, more research will be needed.

The Bottom Line

One of the essential systems in our body is the endocannabinoid system. It has a significant role in homeostasis in the body with a good sphere of influence. This system also plays significant roles in brain function, apoptotic diseases, and other functions. Its contribution spans wider than that just maintaining homeostasis. You will appreciate its profound ability to regulate.

With its inhibitory functions, it is a ‘kill switch.’ All the same, its stimulatory and inhibitory roles depend on the influx of cannabinoids. Given the rate at which cannabinoids degrade, the ECS has fewer long-term side effects than most drugs.

The endocannabinoid system might not only offer answers for diseases with unknown cures. It can also alter how we approach medicine. Instead of focusing on invasive pharmacological inventions, we should focus on understanding why the body does not maintain homeostasis.

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