What Is the Endocannabinoid System?

Human beings have been using cannabis for both recreational and therapeutic purposes for thousands of years. But, while humans intuitively understood that it created certain therapeutic effects, both researchers and laymen didn’t know why that was the case—that is, until recently.  

In the early 1990s, the scientific understanding of cannabis and its impact on the body experienced a significant breakthrough thanks to the discovery that human beings naturally produced cannabis-like molecules, which they dubbed endocannabinoids. Since then, in-depth research on the endocannabinoid system (ECS) has broadened our understanding of how and why cannabinoids such as THC and CBD interact with the human body. 

Interested in finding out more about the endocannabinoid system? Read on to discover everything you need to know. 

The Primary Organ Systems 

Prior to the discovery of endocannabinoids, popular belief stated that your body was comprised of 11 organ systems—interrelated anatomical structures with distinct purposes that work in harmony to carry out certain bodily functions or tasks. As one physiology study put it, “the human organism comprises diverse organ systems. Each organ system has its own complex structural organization and regulatory mechanisms that lead to complex transient, intermittent and nonlinear behavior.” 

Traditional teaching and research on the matter included the following systems:

• Respiratory
• Urinary
• Reproductive
• IntegumentarySkeletal
• Nervous
• Digestive
• Muscular
• Endocrine
• Lymphatic 
• Circulatory

Today, some researchers have added the ECS to the list as the 12th organ system, while others argue against its inclusion, stating that it’s not an isolated system such as the vascular or digestive. 

But what does that mean?

In order to better understand the nuances surrounding this debate, it’s helpful to first breakdown what the endocannabinoid system is and how it works.  

What is the Endocannabinoid System?

The endocannabinoid system was first discovered in the early 1990s by Lisa Matsuda, a molecular biologist at the National Institute of Health. Dr. Matsuda and her research team were working to learn more about THC and its impact on the body. During the process, they discovered a complex network of cannabinoid receptors in the central and peripheral nervous systems. Dr. Matsuda was the first person to accurately describe the structure and function of the CB1 and CB2 receptors. Her revelatory paper stated: 

Recent evidence, however, has supported a mechanism involving a G protein-coupled receptor found in brain and neural cell lines, and which inhibits adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. Also, the receptor is more responsive to psychoactive cannabinoids than to non-psychoactive cannabinoids.

They were amazed to learn that this system wasn’t isolated, but rather comprised of a network of ECS receptors distributed throughout the entire body. Together, they formed the single largest cellular communication system in the human body, with the heaviest concentrations in the central nervous system and gut.  

Now, with more than two decades of research conducted, further light has been shed on the inner machinations of the ECS—we now know that it’s not only limited to humans but can also be found in other vertebrates as well. Researchers currently classify the endocannabinoid system in both animals and men as an adaptogenic system, meaning it’s responsible for promoting homeostasis (equilibrium) in the body. 

ECS receptors encompass a wide expanse of the body’s organ systems, resulting in the ECS having enormous sway over the function and regulation of various crucial physiological processes, including: 

• Appetite
• Fertility
• Inflammation
• Memory
• Mood
• Pain
• Reproduction
• Sleep

As you will later learn, when the ECS—a potent homeostatic agonist— interacts with CBD, those processes can be significantly impacted. So, when a person administers CBD oil, they can receive a host of therapeutic benefits.

How Does the Endocannabinoid System Work?

Although there’s been a ton of research conducted on the ECS, scientists still uncover new revelations daily. We do know that it’s made up of three core components:

1. Endocannabinoids
2. Cannabinoid receptors 
3. Enzymes

Cannabinoids

Cannabinoids are chemical compounds capable of attaching to and activating the ECS receptors spread throughout the endocannabinoid system. Two common types of cannabinoids include:

• Phytocannabinoids – Phytocannabinoids are not created by the human body but instead occur naturally within the cannabis plant. It’s estimated that there are more than 100 unique phytocannabinoids, the most impactful being:

• Cannabidiol (CBD)
• Tetrahydrocannabinol (THC) 
• Tetrahydrocannabinolic Acid (THCA)
• Cannabidiolic Acid (CBDA)
• Cannabinol (CBN)

• Endocannabinoids – Also called endogenous cannabinoids, these chemical compounds are produced by the body and work by stimulating the ECS receptors in order to help regulate internal functions. There are two key endocannabinoids that scientists have identified thus far. These include:

• Anandamide (AEA) – An endocannabinoid that plays a crucial role in the regulation of pain, appetite, and fertility. 

• 2-arachidonoylglycerol (2-AG) – An endocannabinoid that is primarily a CB2 agonist, which impacts functions such as mood, energy, pain sensation, neuroinflammation, and cognition.  

Since cannabinoids are fat-soluble and your body is primarily water, if cannabinoids are to move throughout the body and reach their intended destination, they have to be assisted by naturally occurring endocannabinoid transport proteins. 

Cannabinoid Receptors

According to recent research, the human body has two unique cannabinoid receptors—the CB1 and CB2 receptors. These ECS receptors are located in the central and peripheral nervous systems, and can be influenced by both cannabinoids and endocannabinoids. According to a 2008 study: 

CB(1) receptors are present in very high levels in several brain regions and in lower amounts in a more widespread fashion. These receptors mediate many of the psychoactive effects of cannabinoids. CB(2) receptors have a more restricted distribution, being found in a number of immune cells and in a few neurons. Both CB(1) and CB(2) couple primarily to inhibitory G proteins and are subject to the same pharmacological influences as other GPCRs. Thus, partial agonism, functional selectivity and inverse agonism all play important roles in determining the cellular response to specific cannabinoid receptor ligands.

Endocannabinoids attach to either one of the receptors, initiate a reaction, and thus impact the various physiological processes. However, the specific effects of this coupling depend upon the location of the receptor (as well as the type of cannabinoid that binds to it). As Healthline writes: 

Endocannabinoids might target CB1 receptors in a spinal nerve to relieve aches. Others might bind to a CB2 receptor in your immune cells to signal that your body’s experiencing inflammation, a common sign of autoimmune disorders.  

Currently, scientists and researchers believe that the highest concentrations of cannabinoid receptors occur in the central nervous system. Although there’s no hard evidence to prove it, many researchers have hypothesized about the presence of a third undiscovered ECS receptor. 

Enzymes

After 2-AG and anandamide have delivered their chemical message, your body seeks a way to prevent them from indefinitely stimulating the ECS. Some of the spent endocannabinoids are sent off to storage sites for proteins and others are dispatched to two enzymes, which are predominantly responsible for their breakdown:

• Fatty acid amide hydrolase (FAAH) – Helps to degrade anandamide into smaller parts and convert it into arachidonic acid and ethanolamine. This breakdown process is what prevents you from experiencing a constant state of “cannabinoid bliss.” 

• Monoacylglycerol acid lipase – A key enzyme that helps disintegrate endocannabinoids with water. 

It’s theorized that the relatively small group of people who react poorly to cannabis—specifically to its THC—do so because they have lower concentrations of FAAH and thus a higher concentration of anandamide. The addition of cannabinoids further elevates their already abnormal anandamide levels, which likely causes the uncomfortable symptoms some associate with a “bad high” (think paranoia and anxiety).  

The Endocannabinoid System and CBD

In recent years, scientific revelations have helped shift the tide of public consensus in favor of one particular cannabinoid, Cannabidiol (CBD). Dozens of studies over the past two decades (covering CBD and its interaction with the ECS) have posited that this non-psychoactive cannabinoid may have significant potential as a natural, therapeutic alternative to many modern day medicines. 

And unlike marijuanas’ primary cannabinoid, THC, CBD has all of the benefits without the telltale high or any of it’s other psychotropic symptoms. 

Although the field of CBD study is in its nascent stages, there have been several amazing discoveries that have revealed more about the physiological reactions between the ECS system and CBD. There are dozens of ways this occurs, but those most noteworthy include: 

• It augments communication between the ECS and various neurotransmitters. 

• As a phytocannabinoid, CBD doesn’t totally bind to ECS receptors like THC. It performs what is known as an allosteric interaction with CB1, which causes it to still exert influence over the ECS, without causing a psychotropic reaction (the user doesn’t get “high”). 

• CBD influences the activation of TRPV1 receptors.

• It increases anandamide in the body.

CBD comes from the hemp plant. To be considered legal CBD, the plant must not contain more than .3% THC. Scientists make CBD oil by extracting CBD from the plant and then diluting it with a carrier oil (like hemp seed or coconut oil). It can be used to target both external and internal ailments. As such, CBD can be administered in a variety of ways, such as:

• Oil drops
• Lotion
• Tincture 
• Balm

Although research is still underway, all signs point to CBD having a significant positive impact on the ECS, leading to the following therapeutic benefits:

• Easing aches and soreness – CBD has the potential to be used to help people who deal with regular aches, tension, and soreness.

• Reducing tension and stress – CBD has the capacity to help reduce tension, mitigate everyday stress, and ease the central nervous system.  

• Facilitate restful sleep – CBD has the ability to help encourage and initiate healthy, restful sleep. 

• Increase mental function – Although studies are still in their preclinical and clinical phases, CBD appears to be a neurological cognitive enhancer.

CBD For Your Life 

From helping reduce daily stresses, to easing skin blemishes, our growing understanding of the various ways that CBD can create positive interactions with the endocannabinoid system has the medical community abuzz. Although we’re still in the early phases of medical and clinical study, all indications point to the fact that CBD is and will be the go-to ECS facilitator. And, as more revelations emerge, public favorability ratings are only likely to keep growing.  

Are you interested in learning more about the ECS or CBD? If so, we encourage you to visit our CBD blog or talk with one of our experts at Plant People today!

Reviewed by Minchul An

Minchul An is a Clinical Cannabis Pharmacist and MTM Specialist.