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The Endocannabinoid System Explained

We'll be explaining some indepth information about the ECS in this two-part article so strap on your knowledge cap and let's get into understanding what is now considered to be the most important system of physiology inside the body.

If you want to know how the cannabis plant interacts within the body of all mammals, you first need to understand a small amount of neuroscience...

In 1970 a group of scientists were awarded the Nobel Prize for Medicine when they discovered what neurotransmitters do.

Their painstakingly intricate studies were focused on the chemical messengers used by the brain to communicate information throughout the entire body. These messengers are neurotransmitters and they send contact information between nerve cells (neurons) to regulate various effects to the major systems of the body. 

Simply put, neurotransmitters are the messengers that deliver information between neurons and throughout the entire nervous system, including the central nervous system, autonomic nervous system, and the peripheral nervous system - all the way from the receptors on the skin, to the spinal cord, to the brain itself.

Neuroreceptors are specialized protein molecules found inside all cell membranes and these are activated by a neurotransmitter, which allows communication through various chemical signalling.

By 1973, these scientists had discovered that receptor sites in the brain had the ability to bind with opioids, and the discovery of similar receptors for cannabis might have followed soon after. But efforts were thwarted by “circumscribed by the politicized agenda of the National Institute of Drug Abuse, which subsidized studies designed to prove the deleterious effects of cannabis while blocking inquiry into its potential benefits.”

When was the endocannabinoid system discovered?

In 1992, Dr Raphael Mechoulam (the same researchers who found THC to be the main psychoactive compound in cannabis thirty years prior) discovered that all mammals naturally produced what he called endocannabinoids. These endocannabinoids were very similar in chemical composition to the plant cannabinoids found inside hemp and cannabis.

Researchers then discovered the two main cannabinoid receptors in the body identified as CB1 and CB2, which respond in almost the exact same way to endocannabinoids produced by the body to the plant phytocannabinoids. 

the endocannabinoid system explained

Receptors cells are part of a complex network of chemical messengers in the brain. Other such receptor types utilize a variety of different neurotransmitters, such as serotonin, GABA, histamine, dopamine, or narcotic-like endorphins. These receptors are often described like a key fitting a lock, the cannabinoids fit in and activate the ECS.

How do you explain the endocannabinoid system?

The endocannabinoid system (ECS) is an extremely crucial system of the human body, even though it was only recently discovered. The first most important activity this system acts upon is to modulate energy, well-being and pleasure. The second is to slowly nudge the body back to health in the face of injury and disease.

This powerful, yet enormously complex system has generated an incredible amount of research into how it accomplishes these tasks over the last several decades, providing a basic understanding of the scope and width of this system in just the last ten years. 

There is still much to be learned about this system, and it is only beginning to be included in the curriculum at medical schools and incorporated into clinical proactive. An informal 2014 survey of US medical schools showed that only 13 percent of institutions covered it at all in their training of new doctors.

In 1988 researchers discovered the cannabinoid-1 (CB1) receptor. The cannabinoid-2 (CB2) receptor was uncovered about five years later. One year before the CB2 receptor was discovered, a team headed by Dr Raphael Mechoulam was tracking down the first endocannabinoid signalling molecule, arachidonoyl ethanolamide (AEA).

A few years later, they found this compound and called it anandamide, combining the Sanskrit word meaning bliss (ananda) and the chemical name for the key part of the molecular structure of this compound (amide).

The next thing Mechoulam’s group of researchers set out to identify, was the second endocannabinoid-signalling molecule, called 2-arachidonoyl glycerol (2-AG). After searching for the enzymes responsible for synthesizing and breaking down AEA and 2-AG, they found it, more than a decade ago. 

How does CBD affect the endocannabinoid system?

CBD affects the endocannabinoid system by both working through and with this important system of physiology inside the body. Cannabidiol can work directly upon the body by unlocking the cannabinoid receptors and by supplying an out of balance ECS with much needed cannabinoids.

How does CBD affect the endocannabinoid system

Modern science still does not completely understand the ECS, or cannabinoids for that matter, and it may take many decades yet to fully comprehend the enormity and importance of such a complicated system of physiology in the body.

The ECS plays a critical role in the regulation of disease states in the body due to its ability to restore balance when illness or injury occurs. Due to misinformation campaigns about cannabis and its resulting compounds from now almost 100 years ago, hemp will not get you high. Marijuana is the psychoactive cousin of the cannabis plant, whereas hemp which has been grown for a long time, is non-psychoactive, containing less than 1% THC.

In 2013, researchers Pacher and Kunos revealed in a paper that “modulating Endocannabinoid System activity may have therapeutic potential in almost all diseases affecting humans, including obesity/diabetes, metabolic syndrome, neurodegenerative, inflammatory, liver, cardiovascular, skin diseases, gastrointestinal, psychiatric disorders, pain, cancer, chemotherapy induced nausea and vomiting, among many others.” The importance of the endogenous endocannabinoid system to the treatment of our wellbeing is directly related to our survival and cannot be underestimated or overstated.

The endocannabinoid system consists of the following, based on our current understanding:

1. Two receptors

  • Cannabinoid-1 (CB1) receptor
  • Cannabinoid-2 (CB2) receptor

2. Two signaling molecules

  • Arachidonoyl ethanolamide (AEA or anandamide)
  • 2-Arachidonoyl glycerol (2-AG)

3. Five enzymes

  • DAGL-a (for synthesis of 2-AG)
  • DAGL-b (for synthesis of 2-AG)
  • NAPE selective phospholipase-D (for synthesis of AEA)
  • MAGL (for breakdown of 2-AG)
  • FAAH (for breakdown of AEA)

There are several other possible ways that AEA can be synthesized which are currently being explored. It has also become clear that the endocannabinoid system is not confined to solely working within its own boundaries. 

It unsurprisingly appears to interact robustly with several other non-cannabinoid systems to accomplish tasks of regulating disease and well-being, including the endorphin system, the vanilloid system (the system responsible for transforming pain from acute to chronic), and the immune system.

When the endocannabinoid system modifies these other parts of our physiology, it begins to regulate pain, inflammation, bone health, formation of new nerve cells, mood, fat and sugar processing, energy, hormone balance and brain health.

The endocannabinoid system has a range of remarkable and unique abilities and actions. AEA and 2-AG are what is considered “on demand” substances. They exist as common, spare molecular parts until CB1 and CB2 receptors increase in the central nervous system or in other organ structures in the body. 

When this happens, the transmitters are constructed on demand, work within seconds, and disappear into spare parts again. They are gone almost as fast as they appear, making them quite challenging to watch and locate, hence one reason we’ve taken this long to find such an important system. Kinda like the man behind the curtain from the Wizard of Oz.

What is the role of the endocannabinoid system?

The role of the endocannabinoid system to maintain order and balance (homeostasis). This extends to all of the major essential systems from the immune system to the reproductive and lymphatic.

We hope you've found this content of value, and that is better helps you to understand how the ECS works with the CB1 receptors for anxiety, mood stabilization, and support homeostasis.

Click here to read part 2 of The Endocannabinoid System Explained

The fact is the ECS is important, and it needs a supply of cannabinoids to stay healthy and in balance, itself. This is why hemp has exploded in popularity in recent years as more people understand there's no psychoactive component, with all the rich cannabinoids nature intended.

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