10 Things to Know About the Endocannabinoid System (ECS) in 2023

So little is known about  the largest receptor system in the human body which is the endocannabinoid system (ECS). Most sources indicate that the ECS was discovered barely three decades ago, in 1988. 

Since then, scientists from around the world have made progressive discoveries about this dynamic system and its significance in health and disease.

The number of published studies and articles on the ECS have spiked significantly in the last decade spurring a growth in public interest in the subject. There are even suggestions that this “ seemingly abstruse” system could indeed be the most important system in the human body, given its large influence. Raphael Mechoulam who is considered as a founding father of medical cannabis had this to say about the ECS.

“Two eminent scientists said that the endocannabinoid system is involved in essentially all human disease. This is a very strong statement, but it seems to be correct.”

For sure, scientists are just beginning to come to terms with the breadth and depth of influence of the ECS and its implications on health and disease. 

Here are 10 things that we thought you should know about the ECS in 2023

1. The ECS is Present in Both Vertebrates and Invertebrates
2. Most sources indicate that the ECS was discovered  in 1988
3. The ECS is made up of three parts: endocannabinoids, receptors, and enzymes
4. The ECS is the largest receptor system in the human body
5. The ECS maintains balance or “homeostasis” in the human body
6. The first endocannabinoid was discovered in 1992 by  Lumir Hanus a Czech analytical chemist
7. A deficient endocannabinoid system may trigger some chronic conditions 
8. Compounds in cannabis such as CBD and THC  influence the ECS
9. The ECS forms the basis for medical cannabis
10. The ECS is not taught in most medical schools

The ECS is Present in Both Vertebrates and Invertebrates

Earlier on, it was believed that the ECS was only present in animals that have a backbone aka mammals. It has now emerged that invertebrates such as leeches and mollusks. It is however more pervasive in mammals.

The ECS Was Discovered in 1988

The journey towards the discovery of the ECS started in 1964 when THC was discovered. Scientists became intrigued with how the cannabis-derived compound was able to exert such profound effects on the human body. 24 years later and in 1988, the endocannabinoid system was discovered by the scientists Allyn Howlett and William Devane during a government-controlled study at Saint Louis University School of Medicine . It was identified as the basis for the effects of THC as well as other phytocannabinoids.

The ECS Has Three Components: Endocannabinoids, Receptors, and Enzymes

From what science has revealed so far, the ECS is made up of three primary components that are spread throughout the central and peripheral nervous system; endocannabinoids (ligands), endocannabinoid receptors, and endocannabinoid enzymes (synthesizing and degrading). The endocannabinoids are synthesized by enzymes in the system and interact with endocannabinoid receptors to produce certain effects in the body. Once they have finished their role, they are degraded and removed from the system. The ECS has been described as a “lipid signaling system.” 

The ECS has two types of receptors which are CB1 and CB2. CB1 receptors are abundant in the central nervous system while CB2 receptors are abundant in immune cells. The primary endocannabinoids that have been identified are anandamide (bliss molecule) and 2-AG.  Anandamide is degraded by the enzyme FAAH while 2-AG is degraded by the enzyme MAGL.

The ECS Has the Largest Receptor Network in the Body

The ECS has an extensive network of receptors that are spread out in almost every part of the body including the CNS. The endocannabinoid receptors act like “traffic cops”; whenever a physiological parameter is exceeded they initiate immediate feedback to restore balance. This wide network of receptors support the far reaching effects of the ECS. 

The ECS Maintains Homeostasis in the Body

The ECS is a “regulatory” system that is involved in various important functions in the body. The primary role of the ECS is to maintain a state of homeostasis or physiological balance in the body. Terms such as endocannabinoid tone have emerged and are used to describe the overall state of the ECS in terms of the density and function level of its components.

When the ECS senses an imbalance, it triggers a cascade of events along signaling pathways to restore balance. For example, when the body temperature is too high, the ECS will trigger mechanisms to ensure that temperature is restored to normal parameters. Scientists are interested in the implications of the ECS on the following vital functions:

• Pain
• Sleep
• Hunger
• Metabolism and food intake
• Hormonal function
• Reproduction. Fertility, and pregnancy
• Memory
• Nausea and vomiting
• Immunity
• Moods
• Neurological function
• Cancer progressionThe First Endocannabinoid was Discovered in 1992 

The first endocannabinoid was discovered in 1992 by  Lumir Hanus, a Czech analytical chemist and William Devane, an American pharmacologist. They named the molecule anandamide, from the word sanskrit which means bliss. Hence, anandamide is also referred to as the bliss molecule.

Clinical Endocannabinoid Deficiency May Trigger Chronic Disease

The body may in some cases have a deficiency of endocannabinoids. This state which is described as clinical endocannabinoid deficiency syndrome (CECD) has been linked to some chronic conditions. One study that investigated the concept of CECD found that it could be the underlying trigger for chronic and treatment resistant conditions including migraines, irritable bowel syndrome, and fibromyalgia. The researchers further suggested that this could possibly explain how cannabis provides benefits for these conditions. 

Phytocannabinoids in Cannabis Interact with the ECS

The cannabis plant has hundreds of bioactive molecules mostly made up of phytocannabinoids and terpenes. Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two most investigated phytocannabinoids. Scientists have discovered that phytocannabinoid are able to mimic the actions of endocannabinoids that are produced naturally in the body. Hence, they are able to support the role of the ECS in maintaining homeostasis. This forms the basis of medical cannabis. 

THC primarily binds to CB1 receptors in the brain. Alongside providing therapeutic benefits THC also causes psychoactive effects by altering the state of the mind to induce euphoria. CBD interacts indirectly with both the CB1 and CB2 receptors. Because it does not bind to the CB1 receptors it does not cause psychoactive effects. 

The ECS Forms the Basis For Medical Cannabis

Medical cannabis has gained significant traction in the last decade due to discoveries in science about the role of the ECS and how cannabis can influence this system. To date, 37 states have legalized medical cannabis programs that allow patients to access cannabis-based treatments. 

Here are some of the conditions that have been approved for medical cannabis treatments in the US: 

• Cancer
• Neuropathic pain
• Multiple Sclerosis
• HIV/AIDS
• Diabetes
• Multiple Sclerosis
• Epilepsy
• Crohn’s disease
• Alzheimer’s disease
• Joint degeneration
• Nausea and vomiting in terminal illness
• Anxiety
• Depression
• Sleep disorders
• Mood disorders

Medicinal cannabis may also be used as adjuvant therapy to improve the efficacy of other drugs. For example, patients who are on opioids for pain management can use medicinal cannabis to reduce the amount of opioids that they are taking. This also has a positive impact on opioid-related side effects.

The ECS is not Taught in Most Medical Schools

A recent survey involving physicians who are affiliated with the Society of Cannabis Clinicians found that only 1 participant out of 37 participants learned anything about the ECS in medical school. Most clinicians turn to conferences to acquire medical cannabis knowledge. At the same time, most physicians graduate from medical school without knowing anything about the ECS, simply because this vast and dynamic system has been excluded from medical school textbooks. 

With those ten points, you probably know more about the ECS than a good number of people working in healthcare. And we promise to keep you updated as science reveals more with time.

The ECS is still being studied and there is a lot that remains unknown about this system. So far, preliminary studies have shown that this system plays a significant role in maintaining health and well-being.  It is also clear that phytocannabinoids from cannabis have far reaching effects on the ECS, this forms the basis for medical cannabis. 

Endocannabinoid System (ECS) FAQS

• What is the endocannabinoid system?

The endocannabinoid system (ECS) is a body system that comprises a vast network of cellular receptors and endogenous ligands that work together to regulate vital functions in the body, ensuring that physiological parameters are adhered to and the body remains in a state of homeostasis. 

• How many types of receptors does the ECS have?

So far, two types of endocannabinoid receptors have been identified; CB1 & CB2 receptors.

• Where are CB1 receptors located?

CB1 receptors are perhaps the most abundant type of (G-protein coupled) receptors that are located in different parts of the CNS. They mediate most of the psychoactive effects of cannabinoids. They are also found in minimal amounts in other parts of the body.

•  Where are CB2 receptors located? 

CB2 receptors are found in immune cells and some neurons. They are also present in minimal amounts in other parts of the body including the brain. 

• How many types of endocannabinoids are there?

So far, two primary types of endogenous cannabinoids have been identified; anandamide and 2-AG. Researchers are exploring other possible endocannabinoids but so far none other has been elucidated. 

• What is anandamide?

Anandamide, a fatty-acid neurotransmitter, was the first endocannabinoid to be discovered. It is referred to as the bliss molecule because it triggers happiness and joy when it binds to CB1 receptors in the brain.