Introduction to the Endocannabinoid System

Introduction to the Endocannabinoid System

Introduction to the endocannabinoid system

The endocannabinoid system (ECS) is a broad and complex network of cell-signaling receptors discovered in 1988 by the American chemist, Allyn Howlett, Ph.D. when she explored a large grouping of receptors in the brain that responded to THC, a well-known cannabinoid. Cannabinoids are compounds found in the cannabis plant.

Research still needs to be done in order to fully understand the ECS, but we already know it impacts the regulating of a range of bodily functions and processes, including:

  • Coordinated Movement
  • Emotions
  • Memory
  • Pain
  • Pleasure
  • Reproduction and Fertility
  • Sleep
  • Appetite

All humans have an ECS, and it is constantly active in your body even if you don’t use cannabis.

Read on to learn more about the ECS, including how it works and how it interacts with CBD.

How does the Endocannabinoid System (ECS) Work?

The ECS can be broken down into three fundamental parts: endocannabinoids, receptors, and enzymes.


Endocannabinoids are molecules made in your body that are similar to cannabinoids found in the cannabis plant.
Researchers have discovered two major endocannabinoids:
  • Anandamide (AEA)
  • 2-arachidonoylglyerol (2-AG)

These endocannabinoids serve as primary messengers across nerve synapses and signal neurons to communicate with one another. They modulate the flow of neurotransmitters, keeping the nervous system operating properly and maintaining homeostasis in response to imbalances caused by injury or disease.

The body produces endocannabinoids as needed, which makes it difficult what levels constitute an endocannabinoid deficiency.

Endocannabinoid receptors

Endocannabinoid receptors are found throughout your central nervous system, immune system, and within tissues of the brain, gastrointestinal system, spleen, endocrine system, and circulatory system. Endocannabinoids bind to them in order to signal that the ECS needs to take action. There are two main endocannabinoid receptors:
  • CB1 receptors, which are primarily located in the central nervous system and affect many brain functions including movement, anxiety, stress, fear, pain, appetite, reward, and motor control. The activation of CB1 receptors is responsible for psychoactivity.
  • CB2 receptors, which are mostly found in your peripheral nervous system, blood cells, the spleen, and in connective tissue. They control the release of cytokines that are linked to inflammation during illness or after injury. Activation of CB2 receptors does not cause psychoactivity.

Endocannabinoids can bind to either type of endocannabinoid receptor. The resulting effects are dependent on where the receptor is located in the body and which endocannabinoid binds to it.

For instance, endocannabinoids might bind to CB1 receptors in a nerve to regulate pain. Other endocannabinoids might bind to a CB2 receptor in your immune cells to signal that your body is experiencing inflammation due to a disease.


Enzymes break down the endocannabinoids after they have finished carrying out their function. There are two key enzymes responsible for this:
  • Fatty acid amide hydrolase, which breaks down AEA
  • Monoacylglycerol acid lipase, which typically breaks down 2-AG

What Function Does the ECS Perform?

The ECS is widespread in the human body. Studies have associated the ECS to the involvement with the following bodily processes and disorders:
  • Appetite
  • Learning and memory
  • Anxiety
  • Depression
  • Schizophrenia
  • Stroke
  • Multiple sclerosis
  • Neurodegeneration
  • Epilepsy
  • Addiction
The ECS is also known to be involved in the following physiological and pathological conditions in the peripheral nervous system and peripheral tissues:
  • Pain
  • Energy metabolism
  • Cardiovascular functions
  • Reproductive functions
  • Inflammation
  • Glaucoma
  • Cancer
  • Liver disorders
  • Musculoskeletal disorders

Since its discovery and subsequent studies over the past three decades, the ECS has been shown to be possibly the most important retrograde neurotransmission system in the human body, responsible for maintaining a myriad of bodily functions and involved in the natural maintenance of health and wellness.

How does THC and the ECS interact?

Tetrahydrocannabinol (THC) is one of the major cannabinoids in the cannabis plant. The compound was isolated, along with CBD, in 1964 by Raphael Mechoulam, Ph.D. and Yehiel Gaoni, Ph.D. at the Weizmann Institute. In 1992, Mechoulam’s lab discovered a chemical in the brain that mirrors the effect of THC and named it anandamide after the Sanskrit word for bliss, Ananda.

Anandamide and THC side-by-side, image by NIDA

When THC enters the body, it binds to ECS receptors in a similar way as the endocannabinoid anandamide. Anandamide is thought to intensify sensory experience, stimulate appetite, temporarily blot out short-term memory, and create feelings of pleasure. THC may also cause paranoia and anxiety in some cases.

How does CBD and the ECS interact?

Cannabidiol (CBD) is another major cannabinoid found in the cannabis plant. Unlike THC, CBD in non-psychoactive so it doesn’t make you “high” and CBD doesn’t typically produce negative side effects.

Experts aren’t completely sure how CBD interacts with the ECS. Research into the how CBD works is limited because in the 1970s all types of cannabis, including hemp, were outlawed in the United States as part of President Nixon’s War on Drugs.

Researchers believe that CBD does not have a direct effect on CB1 and CB2 receptors, rather it signals the body’s endocannabinoids to activate these receptors thereby increasing their effect on parts of the body that surround them.

CBD triggers the ECS to release 2-AG, which stimulates CB1 and CB2 receptors which enhances the overall effect of CBD on the body. Other receptors found to be responsive to CBD include the following:

Serotonin Receptor

CBD activates 5-HT1A serotonin receptors found in the central nervous system and peripheral nervous system. This receptor can have a positive effect on many conditions such as anxiety, depression, pain, addiction, nausea, appetite, sleep, and more.

Vanilloid Receptor

CBD also activates the vanilloid receptor, also known as the TRPV-1 receptor, found in both neural and non-neural cells. Studies indicate that it can mediate inflammation, pain, and body temperature.

Adenosine Receptor

CBD also activates the adenosine receptor, which can produce anti-anxiety effects. This receptor also provides a number of health benefits, including improving cardiovascular function, reducing inflammation, and others. It can also enhance brain health and function by down-regulating the production of dopamine, glutamate, and other neurotransmitters.

GPR55 Receptor

Research performed by the University of Aberdeen shows that CBD blocks the GPR55 receptor in the brain, which can help slow down osteoporosis and possibly limit the spread of cancer.

Can you get an endocannabinoid deficiency?

Some experts believe in a theory known as clinical endocannabinoid deficiency (CECD), which suggests that low endocannabinoid levels in your body or an imbalance in the ECS can lead to the development of certain medical conditions.

A study reviewing over 10 years of research suggests the CEDC theory could explain the development migraine, fibromyalgia, and irritable bowel syndrome. These conditions currently do not have a clear underlying cause, and they often occur alongside one another, leading researchers to believe that a treatment involving the ECS may be a crucial remedy for these conditions.


The ECS plays a crucial role in maintaining and promoting the healthy upkeep of many bodily processes. More research is required, but experts are gaining a clearer knowledge of the ECS, which could eventually lead to breakthrough treatments for many conditions.

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