The endocannabinoid system (ECS) is a command-and-control set of biochemical communications between the endocannabinoids produced naturally by the human body and the receptors that are involved in processes such as thinking, memory, coordination, pleasure, and time perception.


In 1988 a government-funded study at the St. Louis University School of Medicine by Allyn Howlett and William Devane determined that the mammalian brain has receptor sites that respond to compounds found in cannabis. These receptors, named cannabinoid receptors, turned out to be the most abundant type of neurotransmitter receptor in the brain.

In 1990 it was announced that a team lead by Lisa Matsuda at the National Institute of Mental health had mapped the DNA sequence that encodes a cannabinoid receptor in the brain. Matsuda was also able to clone this receptor. This opened doors and led to the development of knockout mice that lacked the G-protein coupled receptor.

The discovery of these receptors resulted in the uncovering of naturally occurring neurotransmitters called endocannabinoids. Over a handful of endocannabinoids have been identified, along with another handful of G-protein coupled receptors that interact with these endocannabinoids.

In the pursuit of unearthing the metabolic pathways of phytocannabinoids and endocannabinoids, scientists came across an unknown molecular signaling system within the body that is involved in regulating a broad range of biological functions. They called this system the ECS. When an imbalance is detected within our internal environment, the body synthesizes endocannabinoids that interact with the cannabinoid receptors. The reasons as to why this condition occurs range from our body not synthesizing enough endocannabinoids, to our bodies not producing enough cannabinoid receptors, to an abundance of enzymes that break down cannabinoids, or to outside sources such as foods and medications that decrease ECS signaling.

The role of the ECS

Endocannabinoid receptors are concentrated in the brain, but are also present in nerve tissues all over the body. When a condition such as an injury, fever, or infection disrupts the body’s homeostasis, the ECS helps restore the body’s homeostasis.

The ECS plays a significant role in the normal functioning of the body’s systems, which include:

  • Central nervous system
  • Cardiovascular system
  • Gastrointestinal system
  • Reproductive system
  • Skeletal system
  • Immune system
  • Metabolic processes

The ECS is an important mediator in regulating:

  • Memory and learning
  • Appetite
  • Stress response
  • Pain sensation
  • Mood
  • Sleep
  • Inflammation
  • Drug addiction

How does CBD interact with the ECS?

Finally, we got to the effects of the CBD. As we shall see, the way it impacts on the endocannabinoid system is complex. The first surprise may be the fact that CBD has a rather low affinity for endocannabinoid receptors. This means that for the receptors the CBD is not a first-choice compound, they definitely prefer either the innate anandamide or psychoactive THC.

It turns out that CBD is also a strong negative allosteric modulator of the CB1 receptor. We can observe the most spectacular effects of these features in the presence of THC. Among many other functions, it is responsible for the emergence of inflammation. In the case of CB2, we are again dealing with the opposite effect of THC and CBD. While the former is responsible for receptor stimulation, CBD is an inverse agonist of the CB2 receptor, thus it weakens its efficiency. The anti-inflammatory properties of the CBD can be attributed to this very mechanism, yet but it is worth noting that it has been shown that cannabidiol is actually a quite a weak inverse agonist of CB2, so its impact on the receptor is negligible.

CBD also affects the ECS in two other important ways: by modifying the activity of this system’s enzymes and transport proteins, and thus the concentration of anandamide, the default endocannabinoid. When it comes to systems of the body, we often forget that the system consists not only of the receptors and the dedicated neurotransmitters, but also of the enzymes that regulate the whole mechanism. In the case of the ECS, the one key enzyme is the fatty acid amide hydrolase. As we see, the CBD does not work here directly. Instead, it enhances the effects of the natural element of the system in question.
Another part of the system that shows how broad the effects of cannabidiol is the fatty acid-binding protein. This causes less anandamide to be metabolized; therefore, it remains longer in the system and its effect is enhanced.


The ECS’s role in the homeostatic function of our body is undeniable, and its sphere of influence is incredible. Additionally, it also plays a major role in apoptotic diseases, mitochondrial function, and brain function. The ECS may not only provide answers for diseases with no known cures, but it could change the way we approach medicine.