An In-Depth Look at Our Endocannabinoid System


Your body consists of an endocannabinoid system that contains natural cannabinoid receptors. It produces some endocannabinoid molecules or lipid ligands that bind to your endocannabinoid receptors. Endocannabinoids ("endo" means from within) system molecules are naturally similar to those from a cannabis plant such as THC or CBD.

The endocannabinoid system (ECS) is a vital physiological system in your body that plays crucial roles in maintaining your health and influencing the functions of other body systems.

To know more about the endocannabinoid system, take a walk with us to divulge more on the subject.

Endocannabinoid System Overview
A Brief History of the Endocannabinoid System 1963 - 1964

One professor of Medicinal Chemistry, Dr. Raphael Mechoulam, who is a natural product chemist and his team, started the study on the cannabinoid chemistry. The aim was to understand the science behind the cannabinoids and later perform clinical trials on them.

The "father of medical cannabis" (a reputable name given to Dr. Mechoulam for his hard work in researching cannabinoids), and his team were successful in that study together with the clinical trials.

The project was culminated by their first written paper, which clearly explained the structure of cannabidiol.

After that, the team isolated THC in its pure form and later managed to isolate CBD.

Quoting Dr. Mechoulam, "some distinguished chemists" were unable to identify cannabidiol structure as well as isolating it in its pure form even after several trials.

The success of the research was the epitome of the study and the opening of many other discoveries. It also sparked interest in cannabinoid health benefits to the body.


1970 was the year the endogenous chemicals that bind to endorphins receptors were discovered. Some scientists speculated that if morphine-like receptors were present in the body, it would be evident that it should provide molecules or ligands to bind with the receptors.

The assumption was correct.

After further research, the researchers confirmed that they were not only endorphins receptors in the body but also the morphine-like molecules. The two would complete signals transmission in the body by binding together.


After working extensively to delve on every research findings and lab results, Dr. Allyn Howlett solidly concludes with evidence that cannabinoid receptors exist in a human body.


1990 was the year scientists managed to clone cannabinoid receptors in rats and humans. After cloning the receptor, they named it CB1 (cannabinoid 1).

CB1 is a receptor predominantly found in the brain and the peripheral nerve terminals.

Before cloning the receptor, researchers had to identify and mark an endocannabinoid receptor in a rat's brain that was THC sensitive and had a DNA sequence. The idea of cloning the receptor was to closely monitor it to determine which molecules were binding to the receptor to activate it.

To be more precise on whether the THC compounds were binding on CB1 receptors, the researchers had to remove such receptors from their model genetically. They then exposed the rat to THC compounds, which could not be psychoactive since they had no receptors to bind with them.

The research concluded that some endocannabinoid compounds were present in the body for binding to endocannabinoid receptors.


The discovery was a precursor to other significant developments. Equipped with the knowledge that there must be some endocannabinoid molecules in the body, Dr. Raphael Mechoulam resolved to find more about them.

The argument was that the receptors could not be present waiting for an external molecule, probably from a cannabis plant, to activate the receptors. No, it meant that some internal compounds must be in existence. Once Dr. Mechoulam reached that decision, he expounded on his research to find the cannabinoid compounds.

The result of the research was the isolation of the first endocannabinoid molecule, which they categorized in the CB1 receptor. The researchers named the new finding as endocannabinoid anandamide, from the word "Ananda." It is a word borrowed from Sanskrit language, meaning extreme joy.

Although endocannabinoid anandamide and THC are chemically different, they contain similar activity.


1993 was the year of the discovery and the cloning of CB2 receptors. The receptors mostly exist in the immune system and the nervous system. Although there are hundreds of other endocannabinoid receptors, CB1 and CB2 are the most known.


1995 was the year Dr. Raphael Mechoulam, and his team discovered a new compound. The team named the endocannabinoid compound as 2-arachidonoylglycerol (2-AG). The molecule has a close relationship with anandamide.

The newfound compound can bind to the two receptors CB1 and CB2.

The discovery of the two compounds further led to more studies, especially the THC metabolic pathways. It is then that the scientists discovered a system responsible for the body's physiological activities.

They named the incredible system as the endocannabinoid system.

What is the Endocannabinoid System?

The endocannabinoid system (ECS) is an intricate body system that involves some compounds and receptors to regulate homeostasis in the body.

The molecular system regulates other systems and body activities, depending on the receptor involved.

The endocannabinoid system got its name after the cannabis plant. Discovering cannabis in plants was a stepping stone to endocannabinoid system discovery.

While studying cannabis and its benefits in the body, the researchers stumbled on a new finding. They discovered the endocannabinoid system.

The system is essential in controlling physiological processes and health by maintaining your body cells. It covers almost the entire body, including the immune system, organs, brain, glands, and connective tissues.

Every cell contains a receptor that is activated by specific and matching compounds. For instance, serotonin compounds would bind to serotonin receptors, glutamate to glutamate receptors. Endocannabinoids would bind to endocannabinoid receptors, and so on.

The endocannabinoid system is unique since it contains two receptors, CB1 and CB2. Although the endocannabinoid compounds you may know that bind to CB1 and CB2 receptors are anandamide and 2-AG, there are others - more than a hundred in the body.

The anandamide compound binds to the CB1 receptor, while the 2-AG compound binds to the two receptors, CB1 and CB2.

The binding of endocannabinoid compounds to their respective receptors activates physiological responses vital for maintaining your cells' health, homeostasis, and others such as regulating appetite.

What is the Location of Cannabinoid Receptors?

Unless the researchers discover other endocannabinoid receptors in the future, we continue believing that the system contains only two receptors, CB1 and CB2.

The receptors are located all over your body, including the spinal cord, brain, immune system, organs, skin, and the peripheral nervous system.

The Location of CB1 Receptors and Roles

The CB1 receptors exist predominantly in the brain's nerve cells, spinal cord in both central nervous system, peripheral nervous system, endocrine gland, spleen, gonads, and gastrointestinal tract, and the urinary tract.

When endocannabinoid molecules bind to CB1 receptors, various physiological activities take effect. Some of the physiological functions are appetite, memory, sleep, mood, pain, and temperature regulation.

The Location of CB2 Receptors and Roles

CB2 receptors are mostly present in the immune system, such as in the white blood cells, spleen, and the tonsils. The primary role of cannabinoid CB2 receptors in the immune system is to release and balance cytokine.

Activating CB2 receptors can have anti-cancer and anti-inflammatory effects since they most exist in the immune system.

Besides the two cannabinoid receptors, CB1 and CB2, scientists suspect the existence of a third receptor. The study is still ongoing to locate the third receptor and to clarify its function.

What is the Role of the Endocannabinoid System?

The endocannabinoid system is vital in modulating most of the body processes. The key features in the endocannabinoid systems are the receptors CB1 and CB2, endogenous cannabinoids or ligands, and enzymes.

The system modulates the functions of the immune system, brain, and endocrine, among others.

The endocannabinoid system can also link the external and internal stimuli perception to differentiate the neurophysiological effect from the behavioral outcome.

Therefore, the endocannabinoid system guard against stress by allowing the adaptation of organisms to environmental changes. It also regulates hormone secretion in the reproductive system.

Other functions of the endocannabinoid system include regulating:

  • Energy homeostasis
  • Metabolism of glucose in the muscle cells
  • Cardiovascular processes
  • Release of neurotransmitter
  • Gastrointestinal functions
  • Bone mass maintenance
  • Pain intensity
  • Inhibition of tumor cells
  • Neurons protection
  • Inflammatory response

There is no doubt that the endocannabinoid system is involved in almost every bodily function as a critical player of homeostasis.

How Does the Endocannabinoid System Work?

You can only understand how the endocannabinoid system works if you can first learn how the nerve cells transmit their signals.

Neurons Signals Transmission

It is evident that the endocannabinoids are extensively distributed in the body and are the most active molecules, making the endocannabinoid system unique.

Every nerve cell in your body communicates by transmitting signals. When a nerve cell or neuron is electrically charged or stimulated, it releases a chemical from its axon's presynaptic terminals. The compound can either be neurotransmitters, molecules, or hormones.

The chemical moves forward from the presynaptic terminal to cross through the synapses (the gaps between nerve cells). The compound binds to the receptor's postsynaptic end of the nerve cell to pass on the signal.

The process repeats up to when the signal gets to the brain.

The brain responds to the message by sending instructions or activity to the body in regards to the stimulus.

Retrograde Signaling

At this point, the endocannabinoid system becomes active. The system works in reverse of the first process of the signal journey to the brain.

The fat cells in the brain nerves release endocannabinoids. The molecule moves in reverse across the synapse to bind to the receptor's presynaptic side.

The reverse process, which is known as retrograde signaling, becomes interesting when the stimulus activates the endocannabinoid system to free its compounds.

The postsynaptic nerve cell releases the reverse signal, which is an endocannabinoid molecule to bind to the presynaptic side of nerve receptors CB1 or CB2.

The best part of the endocannabinoid system is when the retrograde signaling slows down the previous presynaptic activity of sending signals to the brain.

The process continues until the molecule reaches the relevant receptor in the targeted area of your body.

The Therapeutic Role of Receptors CB1 and CB2

The endocannabinoid receptors CB1 and CB2 play significant roles in therapy to various health conditions such as neurological and chronic pain.

For instance, when there is a health condition such as pain in the body, it excites the receptors to transmit a message to the brain by being overactive, causing homeostasis imbalance.

Such an imbalance can result in anxiety or stress.

The endocannabinoid system reacts to the problem by releasing endocannabinoids. The signal binds to the receptors through the retrograde process to cause cessation of the production of pain neurotransmitters.

The "dampening down" of neurotransmitters during the 'retrograding' or reverse process, causes endocannabinoid neuron receptors to initiate the balancing of homeostasis in the body.

It means that the endocannabinoid system can quiet or stop the signals to the brain by countering with the retrograde signaling.

Another example concerns the immune system. In case of an injury, the body cells respond to the damage by releasing cytokine protein.

The cytokine takes on the matter by demanding that immune cells from other cells to counter the problem. The release of the immune cells continues to flock to the injury-causing inflammation until another anti-inflammatory protein counters the cytokine production.

Cytokine proteins are essential responses to injury, inflammation, infection, and other health issues.

It does not mean that inflammation is a health problem. It is a defense against pathogens and other health attacks.

The inflammation becomes a problem when it overreacts to worsen the situation and to cause more injury.

Some health conditions, such as rheumatoid arthritis, IBD (inflammatory bowel disease), and celiac disease, are the result of inflammation.

The CB2 is a receptor in the immune system. The endocannabinoids released for inflammatory cases bind to the CB2 receptors of the immune cells that are producing cytokine protein.

The receptors respond by effecting immune cell apoptosis or cell death to cause anti-inflammation. Healing can ensue when the endocannabinoids control the inflammation.

The endocannabinoid system also has a huge role in balancing your blood pressure, either by lowering high blood pressure or raising blood pressure when low.

 The Endocannabinoids - What are they?

We have discussed at length about the endocannabinoid in this information. But do you know what it is?

The endocannabinoids are endogenous ligands or molecules that bind to the endocannabinoid receptors CB1 and CB2.

The only two endocannabinoids discovered so far are 2-AG and anandamide. The anandamide, which means joy or bliss, is a short-lasting molecule.

The endocannabinoid system releases the anandamide molecule only when a need arises. Once it fulfills its mission, an enzyme known as fatty acid amide hydrolase (FAAH) degrades it immediately.

The molecule binds to the respective receptor to activate the expected results.

2-AG endocannabinoid is also short-lived. The endocannabinoid system produces it on demand. Just like anandamide, an enzyme called monoacylglycerol lipase degrades it once it has completed its activity.

The 2-AG molecule can bind to either CB1 or CB2 receptors depending on the signal.

Endocannabinoid System Deficiency

The endocannabinoid system is a system that protects other body systems while maintaining homeostasis.

Despite that, it is vulnerable to diseases, and that may cause dysfunction or cause endocannabinoid system deficiency.

In a publication of July 2016, Dr. Ethan Russo argues that all humans have varying endocannabinoid tones. The endocannabinoid levels, production, metabolism, and the state of the receptors determine an individual's endocannabinoid tone.

Dr. Ethan Russo, in his research review, concludes that disorders such as fibromyalgia, migraine, IBS (irritable bowel syndrome) have common pathophysiological, biochemical, and other clinical patterns. Such patterns may point to an underlying deficiency of the endocannabinoid.

The endocannabinoid system's primary role is to modulate pain in the body. Some of the health conditions we have mentioned above share a common symptom - severe pain.

A dysfunctional endocannabinoid system can fail to modulate the pain, leading to chronic and uncontrollable pain.

Other conditions that link to endocannabinoid deficiency are Alzheimer's and Parkinson's diseases.

How to Correct Endocannabinoid System Deficiency

The imbalance of the endocannabinoid system, whether high or low, can cause disorders. Post-traumatic stress, migraines, preeclampsia, and schizophrenia are some of the present health conditions due to low endocannabinoid levels.

On the other hand, obesity and some tumors are examples of the disorders caused by high anandamide levels.

What then can you do to maintain the balance of the endocannabinoid system and regulate homeostasis?

You can correct endocannabinoid deficiency by:

  • Avoid stress factors and practice stress reduction.
  • Include in your diet polyphenol-rich foods like turmeric and nutmeg
  • Eat omega-3 fatty acids such as seafood, spinach, flax seeds, and walnuts.
  • Exercising helps to release anandamide and also to keep you fit and healthy.
  • Overhaul and modify your lifestyle

The use of phytocannabinoids or supplements from cannabis plants to boost your endocannabinoids.

You can also supplement your endocannabinoids by using CBD oil. The oil is essential in boosting and improving the state and functions of your endocannabinoid system.

Using CBD products can also inhibit endocannabinoid degradation or breakdown.

Plant-derived cannabinoids, which are phytocannabinoids, can easily bind to endocannabinoid receptors CB1 and CB2 to stimulate them for better performance.

The THC is a phytocannabinoid similar to anandamide. It binds to CB1 receptors to produce beneficial effects such as modulating pain and sleep, anti-seizure effects (especially in epilepsy disorder), anti-nausea effects, appetite regulation, antibacterial effects, anti-inflammation effects, and others.

THC can also bind to CB2 receptors, although the biochemistry with the receptor is not as successful as in CB1.

How Does CBD Affect the Endocannabinoid System?

CBD, which is a non-psychoactive compound from cannabis, is another potent cannabinoid. It has the same effect as THC.

By now, you know that anandamide endocannabinoid degrades immediately after its activity. You may also know that CBD can slowly but effectively inhibit endocannabinoid anandamide degradation.

What is more interesting about CBD is that it enhances anandamide signals to alleviate some symptoms such as in schizophrenia disease.

Again, CBD regulates and decreases any negative THC psychoactive effect.

Although CBD has low biochemistry in endocannabinoid receptors, it is useful when it binds to other receptors such as serotonin. It can enhance inflammation control, pain regulation, reduce stress, anxiety, and depression.

You can only experience such effects and many more by using high-quality CBD oils from reputable distributors

Other cannabinoid compounds that can activate endocannabinoid receptors for the potential effect on various health conditions are CBDV, CBG, and CBN.

There is new research on CBDA that indicates this oil might have a much more potent effect than all the other CBD oils. Stay tuned to our next article as we dwell on this discovery.


The endocannabinoid system is essential and irreplaceable in your body. Besides assisting other body systems in triggering body processes, it maintains your body's homeostasis. The effects of the system are widespread for therapeutic purposes.

Even though the system is powerful to overcome various disorders such as schizophrenia, epilepsy, and others, it is vulnerable to other problematic conditions such as genetic mutation or nutrition.

Congenital or acquired genetic problems are a drawback to an effective endocannabinoid system.

Nutrition is also a key player in either building or breaking your endocannabinoid system. Keep off unhealthy lifestyles and unhealthy diets to maintain a stable system. What you eat determines a weak or a healthy endocannabinoid system.

The endocannabinoid system is, therefore, prone to endocannabinoid deficiencies, which can lead to some health conditions such as IBS (irritable bowel syndrome), fibromyalgia, and migraine.

However, the deficiency is short-lived if only you support it with external phytocannabinoids from plants such as cannabis. Supplementing your endocannabinoid with plant-derived compounds can improve and even reverse the deficiency.

Using plant-derived CBD in any form such as oil can maintain the anandamide compound of your system by increasing its lifespan. CBD inhibits the enzyme that degrades anandamide and hence to preserve it.

Evidently, external cannabinoid THC and CBD, when used correctly, can boost your endocannabinoid system, especially to increase endocannabinoids.

Use only high quality and organically grown cannabinoid supplements. You can not only improve your homeostasis but promote your body cells' health and strength.

Do you have any questions or comments? Kindly leave us your feedback in the comments section below. We will surely get back to you.

You can also call us through our telephone number 250.468.7685 or write to us at This email address is being protected from spambots. You need JavaScript enabled to view it..

Know more about your body and health by reading other informational health articles from our Island Healthworks Blogs page.

Please, do not forget to share the incredible information with your loved ones.

Yvonne Dollard Perc: Owner of Island Healthworks, Natural Health Practitioner, Teacher, Writer and Editor.
Elizabeth Njuguna: Researcher, Freelance Writer, with a Focus on Natural Health.
Sherry Robb: Print, Web and Social Media Designer specializing in the natural health and fitness industries.

Island Healthworks offers in-person and virtual consultations for assessment of your specific needs, with health & lifestyle coaching, featuring the best of integrative natural health care. To book your consultation, please call 250-468-7685!

This article is intended for educational purposes and the information contained within is not intended to treat, diagnose or cure any disease or health problem. Please seek appropriate medical attention for any health complaints. We cannot take responsibility for your health care decisions. Our intent is only to offer health information to help you with your search for better health. 

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Tuesday, 20 April 2021