What is the Endocannabinoid System? Where is it Located? And, What are its Functions?
By: Franz Aryan
Tags: Hemp, Marijuana, Cannabis, Endocannabinoid System, Cbd

Is it true that we’ve only known about the Endocannabinoid System for about 25 years?

Yes, it is.

Until somewhere around the mid-1990s, we’d known of only the twelve main systems within the body. These are mainly comprised of some of the most pivotal-serving-functions-areas like the circulatory system, nervous system, digestive system, respiratory system, muscular system, and a few more. However, the rising curiosity and probes into knowing exactly how THC i.e. tetrahydrocannabinol — the most active and abundantly used chemical compound in cannabis, works within the body to bring out its various effects.

The research, led by Doctor L.A. Madsuda eventually found that (already) exists a complex and diversified network of receptors that were capable of literally entertaining cannabinoids. Subsequently, the endocannabinoid receptors were called CBR — generally and CB-1 specifically. In humans, CB-1 receptors can be abundantly found in cells within the central and peripheral nervous systems.

However, through another study conducted only a few years later, scientists were able to identify another set of cannabinoid receptors within the body, known today as CB-2 receptors. These receptors are mainly found in the body’s immune system, digestive system, and around a few other major organs.

But, why would the body even have something like the Endocannabinoid System? What was its purpose? Why was it even there? Just for the sake of getting a high? Nah. Invariably, this prompted further inquiry into learning and understanding more about it.

And soon, researchers and scientists also discovered that not only does such an intelligent and highly-regulatory system exist within the body, but that it is also capable of producing its own form of chemical compounds i.e. endocannabinoids to accommodate the receptors.

The first chemical compound discovered in 1992 was a certain type of long-chain, fatty acid (lipid) amide, coined as Anandamide; or, scientifically known as N-Arachidonoylethanolamide. The term Anandamide was inspired by the Sanskrit word ‘Ananda’, which means happiness, joy, or bliss. This was because the chemical compounds were deemed to play an important role in regulating the ECS, which in turn would help regulate several vital functions of the body.

In 1995, the ester of the fatty acid (lipid) amide was discovered as an agonist to the CB-1 receptors and main regulators to the CB-1 receptors. These became known as 2-Arachidonoylglycerol (2-AG).

These were some of the biggest ground-breaking discoveries in the field of medicinal marijuana/hemp and its various uses.

Photo by CDC on Unsplash

So, what exactly is the Endocannabinoid System?

The Endocannabinoid System (ECS) is a naturally-occurring biological system found within the bodies of several vertebrates (birds, fish, mammals, and reptiles) and invertebrate (leeches, mussels, and urchins) species across our habitat. Although, among the several groups, it has been found to be a lot more pervasive in mammalians than in the others.

Through various researches and studies, the ECS has been found to play a pivotal role in the overall regulation of several systems of the body i.e. the ECS assists in allowing the body to maintain a good level of homeostasis so it continues to function optimally.

So, if an external force causes you to feel pain from an injury or a fever due to an illness, your ECS would step-in to help your body return to its normal state i.e. it will balance your body’s homeostasis in a way such that your organs, systems, other parts would help identify and solve impending issues.

The main components of the endocannabinoid system are –

Endogenous cannabinoids

Present within lipid membranes, endogenous cannabinoids, or endocannabinoids are chemical compounds that cause similar effects akin to exogenous cannabinoids like CBD and THC in the body. When required, endocannabinoids are released in one or a couple of rapid enzymatic steps and discharged into the extracellular space, where they can then carry out their functions in neurotransmission.

In simpler terms, our body naturally secretes and releases substances that serve similar functions/purposes to the effect-causing (therapeutic and the high) substances found in cannabis.

The most widely known endocannabinoids are –

1) Anandamide — N-Arachidonoylethanolamide

2) (2-AG) — 2-Arachidonoylglycerol

3) Virodhamine

4) 2-Arachidonoyl Glycerol Ether

5) N-Arachidonoyl-Dopamine (NADA)

It remains difficult to gauge the appropriate levels of these chemical compounds in a body because the body produces them whenever needed.

Endocannabinoid receptors

Endocannabinoid receptors are the receptors that endocannabinoids and/or exo-cannabinoids bind to, to submit a signal to the endocannabinoid system that a certain action needs to be taken by it.

The most widely known endocannabinoids receptors (CBR) are –

1) CB-1 — Abundant in the central nervous system (CNS), particularly in cortex, basal ganglia, hippocampus, cerebellum, heart, blood vessels, liver, lungs, and the digestive system.

2) CB-2 — These highly-inducible receptors can be found in some peripheral regions of the central nervous system, in immune cells, immune tissues, spleen, thymus gland, tonsils, gastrointestinal system, and in some parts of the brain.

3) Transient Receptor Potential (TRP) channels

4) Peroxisome Proliferator-Activated Receptors (PPAR’s)

Depending on the specific need/situation, different cannabinoids may bind with different sets/types of receptors found throughout the body. So, a certain set of endocannabinoids would target CB-1 receptors to relieve pain because of a spinal nerve injury or target CB-2 receptors within immune cells to signal the body to take some action against inflammation.

Both CB-1 and CB-2 cannabinoid receptors are G-protein-coupled receptors (GPCR’s).

Activation of CB-1 or CB-2 receptors exerts diverse consequences on cellular physiology, including synaptic function, gene transcription, cell motility, etc. Source — International Union of Pharmacology. XXVII. Classification of cannabinoid receptors — https://pubmed.ncbi.nlm.nih.gov/12037135/ Both the CB-1 and the CB-2 receptors play important roles in many essential biological processes, including neuronal plasticity, pain, anxiety, inflammation in general and especially neuroinflammation, immune function, metabolic regulation, reward, craving, and bone growth. Source — Mackie K (2006) Cannabinoid receptors as therapeutic targets. Ann Rev Pharmacol Toxicol 46146:101–122

Endocannabinoid (deactivating/degrading) enzymes

Present also within cell membranes, endocannabinoid enzymes are responsible for the degradation of cannabinoids after they’ve carried out their respective function(s).

The most widely known cannabinoid enzymes are –

1) Fatty Acid Amide Hydrolase (FAAH)

2) Monoacylglycerol Acid Lipase (MAGL)

What functions does the endocannabinoid system partake in?

Anxiety and Stress

Appetite and digestion

Metabolism

Inflammation

Learning and memory

Liver functions

Pulmonary system

Reproductive system

To conclude

As discussed, the endocannabinoid system plays some vital roles so the body can continue functioning in the best possible way. Not only does it recognize different types of threats to the body like inflammation, plain, nervous injuries, fever, etc. but it also helps in sending responses in the form of signals so a particular organ/part/system can do what it needs to resolve the issue.

The discovery of the ECS within almost every animal throughout the world is a clear signal that there is always more than what we knew or know. Although, based on what we have been able to learn and understand today, we expect to find a lot more important discoveries when it comes to such almost-mystical arrangements within.

Understanding the endocannabinoid system is important for everyone who has seriously considered understanding how popular cannabis compounds like CBD and THC work in the body; needless to mention now — our very own cannabinoid system.

And lastly, it is slyly relevant for anyone who is familiar with (any of) the various effects of the chemical compounds from cannabis to know about the endocannabinoid system; because if it wasn’t for it, cannabis would quite literally be just another plant.

Happy learning and consumption to you my friend (: