What is the Endocannabinoid System? An Introduction to the ECS

What is the Endocannabinoid System? An Introduction to the ECS

Your guide to the endocannabinoid system: how it works, what it is for, and why it is crucial – not only for cannabinoids and CBD, but also for overall wellness.

Research and studies from all over the Internet give insight into the capabilities of CBD and its effects on the body. But possibly more important than how CBD oil works is why it can affect the human body the way it does.


CBD, like any other cannabinoids from Cannabis sativa, doesn’t work on its own within the body. When CBD molecules enter the bloodstream, they continue to travel and pass through the blood-brain barrier to reach the endocannabinoid system.


But what is the endocannabinoid system exactly? And why is the system necessary for cannabinoids to even work? This guide details this bodily system – mainly how does the endocannabinoid system work, the endocannabinoid system function, and why it is crucial. This is true not only for cannabinoids but also for overall wellness.

A diagram of the human body indicating the positions of CB1 and CB2 receptors in green and blue

What is the Endocannabinoid System?

The endocannabinoid system (ECS), also referred to as the endogenous cannabinoid system, is a complex physiologic network that stretches throughout the human body and helps establish and maintain overall health and wellness.


The endocannabinoid system is not only present inside human bodies but in all vertebrates, including mammals, reptiles, fish, amphibians, and birds. Early research on the ECS shows that the system may have evolved well over 500 million years ago.


It uses complex actions, such as the signaling or transmission of neurons, that affect our nervous system, our immune system, and several of our body’s organs. And it typically serves as countless bridges of communication between the mind and body.


Initially, scientific findings suggested that the endocannabinoid system function was only connected to the brain and nerves; however, throughout the years, researchers discovered that the ECS encompasses several parts of the body, including skin, gastrointestinal tract, bone, tissue, and other biological structures.


And now, modern studies explain the involvement of the ECS with many different physiological functions such as sleep, metabolism, mood, appetite, stress, and general pain – even reproductive and immunological abilities.

How Does the Endocannabinoid System Function?

Even though the scientific community is still working to uncover the secrets of the endocannabinoid system, we currently know that it helps to regulate a broad range of processes.


And even if you don’t use CBD products or cannabis, the ECS still functions and remains active inside your body. For the endocannabinoid system to work correctly, it uses three critical components:

  • Cannabinoid receptors
  • Endocannabinoids
  • Metabolic enzymes

A blue and purple image of a neuron against a black background

What are Cannabinoid Receptors?

The cannabinoid receptors comprise the entirety of the endocannabinoid system and allow it to function. These connectors spread throughout the body – attached to cellular membranes – and are possibly more numerous than any other connective system.


Two known types of cannabinoid receptors that make up the ECS – Cannabinoid Receptor 1 (CB1) and Cannabinoid Receptor 2 (CB2).


CB1 receptors are predominant within our central nervous system (CNS), which contains our brain and spinal cord; they can affect or send transmissions to the connective tissues, neurons, glands, gonads, and organs associated with the CNS.


CB2 receptors are more prevalent with the peripheral nervous system (PNS), consisting of nerve fibers branching from the CNS and stretching to many different organs and parts of the body such as various limbs, skin, muscles, and immune cells.


Cannabinoid receptors work by transmitting information to the inside of the cell regarding conditional changes; this process then starts the most suitable cellular response. And many tissues can have both CB1 and CB2 receptors that link to different actions. They become active primarily through the use of endocannabinoids.

A stylized image of a transparent human body with large long chain molecules inside

What are Endocannabinoids?

Endocannabinoids are one of the two types of cannabinoids that activate the cannabinoid receptors within the endocannabinoid system. But more importantly, they are the cannabinoid molecules that our bodies produce naturally.


Phytocannabinoids, in contrast to endocannabinoids, are cannabinoids synthesized naturally from plants – mainly Cannabis sativa. CBD, cannabigerol (CBG), cannabinol (CBN), and other beneficial cannabinoids that you may find in premium CBD oil capsules or products are phytocannabinoids, as is THC.


Our endocannabinoids, also referred to as endogenous cannabinoids, help to sustain and maintain internal functions. And scientists haven’t quite figured out how many endocannabinoids our bodies typically produce because they only become synthesized when needed.


Two vital endocannabinoids have been discovered through the years:

Anandamide (AEA)

Also known as N-arachidonoylethanolamine (AEA), it is a fatty acid neurotransmitter that has been featured in many scientific reviews that have researched how it affects humans. It is sometimes referred to as the “bliss molecule” because anandamide derives from the Sanskrit word “ananda,” which can mean delight or joy.


Scientists believe that anandamide molecules affect the development of early-stage embryos and memory; it was identified and named first in 1992 by Israeli organic chemist Dr. Raphael Mechoulam.

2-Arachidonoylglycerol (2-AG)

Although 2-AG was already a known chemical compound, scientists later discovered its compatibility with cannabinoid receptors. It was also described first by Dr. Mechoulam along with his student, Shimon Ben-Shabat, between 1994 and 1995. Levels of 2-AG are particularly high in the central nervous system, and it is also found in breast milk and maternal cows.


Both endocannabinoids and phytocannabinoids stimulate cannabinoid receptors by attaching or binding to them. In particular, to answer what is CBD, it’s a non-intoxicating phytocannabinoid that typically connects to CB2 receptors – sending signals to the body parts and organs closely associated with these bodily systems.


On the other hand, THC, which is a psychoactive phytocannabinoid, normally binds to CB1 receptors throughout the central nervous system (CNS). And sometimes, CBD may also attach to CB1 receptors – restricting other molecular compounds from interacting or affecting the functions performed by the CNS.


Without phytocannabinoids, the endocannabinoid system uses our endogenous cannabinoids, which the body only creates when needed, and which have short-range effects and a shortened half-life before their degradation from enzymes.

n image depicting metabolic enzymes

What are Metabolic Enzymes?

The metabolic enzymes are what our body uses to break down endocannabinoids after they have served their purpose; they work by accelerating the chemical reactions within our systems – resulting in the deterioration of molecules.


There are two primary enzymes responsible for breaking down endocannabinoids:

Fatty Acid Amide Hydrolase (FAAH)

Fatty acid amide hydrolase is a serine hydrolase enzyme, one of the most diverse and most extensive enzyme classes. Serine hydrolase enzymes have vital roles in several pathological and physiological procedures. They degrade substances by splitting specific molecular bonds. In particular, FAAH breaks down the endocannabinoid anandamide.

Monoacylglycerol Lipase (MAGL)

Monoacylglycerol lipase is also part of the serine hydrolase enzyme family; it creates a chemical reaction using water molecules to degrade monoglycerides in long-chain fatty acids. And it’s typically used for breaking down 2-arachidonoylglycerol.


These two enzymes make sure that our endocannabinoids become used but don’t last any longer than required. This degradation process makes endocannabinoids unique from hormones or other standard neurotransmitters; they cannot be stored and put away for anticipated use.


Having too many endocannabinoids would probably go against the primary purpose and goal of the endocannabinoid system.

How Does the Endocannabinoid System Work? The Endocannabinoid System Function, Role, and Purpose

Earlier, it was mentioned that the endocannabinoid system helps to maintain health and wellness. And while it does so in many different ways, its primary purpose is to help manage homeostasis.

An artistic expression of the human mind with circuitry going into an outlined human head

What is Homeostasis?

Homeostasis is the stability and balance of our physiological and cognitive functions in response to fluctuations – created internally or externally – that would cause our bodies to behave or perform differently than usual.


The human body actively regulates the biological systems within itself to maintain a confined range of optimum conditions – consistently, even while you’re sleeping or lounging around. Picture a gauge with one half being blue and the other half being red.


The blue half represents some form of deficiency, such as “too cold” or “low blood sugar,” and the red half depicts a surplus like “too hot” or “high blood sugar.” In between those two halves, picture a quarter-sized neutral area with the indicator swaying back and forth only within that small section – not crossing into the blue or red. That’s homeostasis!


We typically maintain homeostasis through negative feedback methods – meaning that only when something changes, the body begins to correct itself. And the endocannabinoid system plays an essential role in that correction.

A color coded pyramid depicting the stages of the homeostatic process


How Does the Endocannabinoid System Work to Support Homeostasis?

The endocannabinoid system serves as a significant molecular network for helping the body sustain homeostasis. The ECS becomes used only when and where it is required because its role is to keep all other systems functioning within the optimal range.


For example, our neurons, also called brain cells, speak with each other by firing electrochemical signals to one another. Every neuron has to be aware of the one currently speaking, so they know when to fire their own signal. When messages are going off one after the other safely, that’s the optimal range of their function.


If a neuron starts to send too many signals at once, the neuron that’s receiving all those transmissions will synthesize endocannabinoids where it’s connected to the hyper neuron. The endocannabinoids make their way to the overacting neuron and attach to its CB1 receptors and send their signals to calm that neuron down – returning things to that optimal range and maintaining homeostasis.


This example also explains how endocannabinoids work as retrograde signals. Information between brain cells typically flows in a forward direction only, from the neuron speaking to the neuron that’s listening. However, the receiving neuron was able to regulate how much input it was getting by sending endocannabinoids backward toward the hyperactive neuron.


Other biological systems similarly work when trying to return to their optimal range of functioning. Another example is how our immune system uses inflammation as a response mechanism to physical damage or infection.


Inflammation is useful when it’s repairing damaged tissue or getting rid of pathogens. The resulting inflamed area is from the immune cells and fluids flowing to the injured site and getting things back to how it used to be – they’re working within that optimal range.


However, if inflammation spills over into perfectly fine areas and organs, or lasts much longer than needed, it can cause much harm. Chronic inflammation is when inflammatory responses remain for too long, and when it starts to attack healthy cells, it becomes an autoimmune condition.


In this example, endocannabinoids become released alongside the immune cells fighting away the bacteria or repairing damaged areas. The signals from the endocannabinoids help to restrict any excessive inflammation, which allows the inflammatory response to work within its optimal range and preserve homeostasis.


There are several moving parts involved with how the endocannabinoid system helps to maintain homeostasis. Though its functions might not have been apparent at its first discovery.

Parts of the endocannabinoid system viewed beneath an electron microscope in blue, purple and yellow

How was the Endocannabinoid System Discovered?

Before the ECS was mapped and found, a discovery from years ago set the stage. Dr. Raphael Mechoulam, the Israeli scientist mentioned earlier, was the first to identify and isolate THC back in 1964.


And because Dr. Mechoulam was able to isolate this cannabinoid, his research led the way for studies into cannabis and its effect on the human body. In a government-funded study in 1988, Dr. William Devane and Allyn Howlett from the St. Louis University School of Medicine discovered receptor sites that responded to cannabis compounds inside the brain of a rat.


The receptors they uncovered, termed cannabinoid receptors, ended up being the most abundant neurotransmitter receptor in the brain, therefore mapping the endocannabinoid system. And finding these cannabinoid receptors eventually guided scientists to the detection of endocannabinoids.


It was also William Devane, along with Dr. Lumir Hanus, that identified the anandamide endocannabinoid in 1992 at the Hebrew University in Jerusalem. Their team also discovered the 2-arachidonoylglycerol endocannabinoid and several other minor neurotransmitters that attach to cannabinoid receptors.

Why is the Endocannabinoid System Important?

The endocannabinoid system isn’t just an important physiological structure within our bodies; it’s an essential network that plays a significant role in the survival of the human body and how CBD interacts with us – whether you’re using CBD daily or as needed or taking the best CBD for sleep.


Some scientists have even implied that low levels of endocannabinoids can lead to the development of harmful circumstances. This condition, clinical endocannabinoid deficiency (CECD) or ECS dysfunction, could help explain why some people have severe issues with their wellness.


Although many serious health conditions have no underlying cause, if ECS dysfunction is a possible factor, targeting the endocannabinoid system or the production of endocannabinoids could become vital. However, more research is required to determine this possibility.

The Endocannabinoid System and Your Body

Overall, the ECS does a significant amount of work to stabilize our bodily functions. It’s a fundamental structure made up of cannabinoid receptors, endocannabinoid neurotransmitters, and metabolic enzymes. And all these pieces work together to help maintain homeostasis.


The ECS uses its endogenous cannabinoids, anandamide and 2-arachidonoylglycerol, to help regulate the functions of neurons, immune cells, and other tissue and organ systems. Phytocannabinoids, such as CBD and THC, can also affect the ECS by attaching to either its CB1 or CB2 receptors – sometimes both.


Because of the ECS’ role to make sure our systems and cells function in an optimal range, it is only used when and where its effects are required. Even though the ECS and its mechanisms were discovered relatively recently, its existence has been traced back to hundreds of millions of years ago with the earliest vertebrates.


The identification and isolation of THC molecules opened the first of many doors to exploring cannabis and how it interacts with the body. This discovery ultimately led scientists to uncover cannabinoid receptors and the endocannabinoids that react to them.


With more research in the upcoming years, the scientific community could potentially pinpoint whether a deficiency of endocannabinoids could be the underlying cause of some severe health and wellness issues. If so, then strengthening the ECS or increasing the output of endocannabinoids can be an imperative option.


Even though CBD and other cannabis-based means can help jumpstart or boost ECS activation, it shouldn’t be viewed as some form of one-size-fits-all alternative approach. There is still much we don’t know about, and scientific research can only go so far with modern technology.


But by understanding homeostasis, the endocannabinoid system function, and the role the endocannabinoid system plays with our internal balance and stability, we can develop and explore alternatives for maintaining wellness. In the future, such options could become standardized methods that are less invasive and more amicable than today’s conventional means.

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