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The Endocannabinoid System and CBD

Posted by Dr. Leslie Mudd on Apr 3rd 2020

The Endocannabinoid System and CBD

Exploring one of the most misunderstood systems in the human body.

The Endocannabinoid System (ECS) is one of the most amazing systems in the human body. We don’t know much about it because the ECS was discovered only recently. But we do know that CBD interacts with the ECS. Before we dig into the subject of the ECS and CBD, let’s first discuss our terminology.

CBD is short for “cannabidiol.” It is one of at least 150 different known cannabinoids present in the cannabis plant. Each cannabinoid plays a role in communicating with the ECS. Hemp is a group of cannabis varieties that contain not more than 0.3% THC by dry weight. When we talk about CBD, we are usually discussing hemp-derived CBD.

CBD oil is made by extracting components from hemp flowers. Then the extract is blended with a carrier oil like MCT coconut oil. It can be used in many applications like oils, capsules, topicals, and edibles.

No matter how you take it, CBD can influence the ECS to impact the body in many meaningful ways. We hope this blog post provides you with the foundation to understand how CBD affects the ECS. And we also hope to show you how CBD has the potential to positively affect many wellness issues we encounter in our daily lives.

What is the Endocannabinoid System?

How does the ECS and CBD work together? The endocannabinoid system (ECS) networks a series of receptors throughout your body to maintain homeostasis and immune modulation. 1 It works by binding with cannabinoids, both endogenous (produced by the body) and exogenous (produced outside the body). Cannabinoids produced by the body are called “endocannabinoids”, ones produced by plants are called “phytocannabinoids.”

The ECS has been described as “an ancient lipid signaling network which in mammals modulates neuronal functions [and] inflammatory processes… The system is able to down regulate stress-related signals that lead to chronic inflammation and certain types of pain…” 2 That’s a very good description. It begins to explain why we need to know about the ECS to understand how CBD works in our bodies.

How is Cannabis involved with the ECS?

The word “Cannabinoid” comes from the cannabis plant. It is the only plant on Earth to produce phytocannabinoids. The most common compounds are THC and CBD. THC is associated with recreational use, while CBD may produce anti-inflammatory and mood stabilizing effects, according to research.

The ECS consists of two sets of receptors, CB1 and CB2 — more on that below. These receptors bind to cannabinoids to help the body bring systems back into balance. These receptors remained invisible to Western medicine for centuries. It wasn’t until scientists began to research the cannabis plant that led scientists to the discovery of the ECS. What they discovered is that the ECS is integral to all sorts of homeostatic functions, such as the modulation of inflammation and pain.

Our research into endocannabinoids is still incomplete. We don’t know if we have identified all the cannabinoids produced inside the body. But we do know the ECS is involved in certain pain responses, specifically nociceptive pain. A full understanding of phytocannabinoids is even less clear.

Most of the study on phytocannabinoids has focused on THC. However, a full inquiry into the effects of THC have been severely limited by legal constraints and politics. Also, the predominant delivery method of THC (via smoking) is unconventional in a clinical setting. This has also proved a hurdle in research.

But there’s more to the cannabis plant than THC. Other phytocannabinoids, like CBD, in combination with terpenes like β-caryophyllene, have lived too long in THC’s shadow. But in the last few years, an explosion of scientific inquiry has begun to unlock the secrets of cannabis and how its components interact with the ECS.

Discovering the ECS

An American chemist named Roger Adams first discovered CBD in the early 1940’s. The U.S Patent Office granted him a patent for his CBD isolation process in 1942. However, the onset of World War II sidelined his research. That work to isolate CBD and THC continued in the 1960’s in Israel by a team led by the now-famous cannabis scientist Dr. Raphael Mechoulam.3

Despite this understanding of these isolated phytocannabinoids, scientists didn’t discover the ECS until 1992. That year at the Hebrew University of Jerusalem, a multinational team discovered the first endocannabinoid, known as anandamide.

While working to understand the metabolic pathways of cannabinoids inside the body, these researchers discovered an unknown signaling system on a molecular level that regulated a wide range of other bodily systems. This was science’s first glimpse of the ECS. 4

How Does the ECS Work?

Scientists are still trying to understand the wide ranging effects of the ECS. Its receptors are found in high concentrations in the brain and gut. They are also found in lesser concentrations throughout the body.

Unfortunately, medical schools still don’t teach students about the ECS.5 According to experts, faculty and administrations don’t want to add new material to an already overloaded curriculum. But if our med schools don’t train new doctors on this fascinating system, they will miss opportunities to diagnose and treat patients using naturally occurring phytocannabinoids like CBD and THC.

The ECS affects each body differently depending upon the concentration of receptors. Cannabinoids bind to the two primary receptor types, CB1 and CB2. CB1 receptors appear concentrated in the central nervous system, while CB2 receptors can be found in peripheral tissues throughout the body. These ECS receptors are members of the same receptor superfamily, from which nearly half of all contemporary drugs use as binding sites. 6

CB1 Receptors

CB1 receptors appear to be concentrated in the central nervous system, particularly the brain. 7 The CB1 receptor doesn’t appear in the entire brain, only certain parts. For instance, CB1 can be found in the hippocampus and associational cortical regions, the cerebellum, and the basal ganglia. However, CB1 receptors are not found in the brain stem, medulla, or thalamus. This may be the reason why high doses of CBD are not life-threatening.

When activated, the CB1 receptor can affect memory, perception, and movement through stereo-selective inhibition of adenylate cyclase activity. Activation of CB1 receptors could be the reason for the mood-altering euphoric effects of THC. This could also be the reason that some people experience negative effects from THC, such as dysphoria.

CB2 Receptors

Unlike CB1 receptor activation, which can cause a person to feel “high,” the activation of CB2 receptors simply doesn’t do that. That’s because CB2 receptors appear to serve a role in non-psychoactive functions like pain modulations, immune function, and inflammation. 8 Evidence shows that CB2 receptor activation reduces chronic pain signaling in preclinical models. 9

CB2 receptors have also been found in the spinal cord, and in regions of the brain relevant to pain response. 10

The Endocannabinoid System and CBD

So, how does CBD communicate with your body’s ECS? Studies characterize CBD as a pharmacological agent with a wondrous diversity of effects upon the body. And amazingly, CBD appears to be very benign. Studies show CBD to be non-intoxicating with a low sedation potential and low abuse risk. Compared to THC, CBD has virtually no psycho-activity. 11

CBD even appears to act as an antidote of sorts for people who ingest too much THC. Or, to put it in more precise terms: CBD appears to behave as a CB1 receptor inverse agonist by mitigating the psychotropic effects of THC. 12

CBD’s anti-inflammatory properties and impact on pain response seems to come from cannabidiol’s agonist activity at CB2 receptors. 13

The ECS and the Entourage Effect

The term “entourage effect” means increased efficacy derived from combining phytocannabinoids and other plant-derived molecules.14

We have the data to back this up. Cannabinoids administered together are more effective at ameliorating pain than the use of a single agent like CBD isolate, according to preclinical and clinical data. 15

What are the components of the entourage effect? Well, we know that phytocannabinoids that have clinically useful properties without psychoactive effects include CBD and other lesser known cannabinoids. Such as THCV, CBG, and CBC.

In addition to these “minor cannabinoids,” terpenes play a role in the entourage effect. Terpenes are molecules that create flavors and fragrances in plants. Also, terpenes share a precursor molecule with phytocannabinoids. The US Food and Drug Administration has designated terpenes to be “generally recognized as safe” (GRAS). 16

Terpenes and the ECS

Terpenes can be quite potent. They can affect animal and human behavior when consumed in low concentrations. And they display unique therapeutic effects. This is how we think terpenes can contribute to the entourage effect of hemp-derived cannabinoid extracts like full spectrum CBD oil.

For instance, the terpene β-caryophyllene (read as “beta-caryophyllene”) is found in a number of plants, including black pepper, cinnamon, and cannabis. This terpene selectively binds to the CB2 receptor at tiny concentrations. This means that the cannabis plant produces at least two different chemicals — β-Caryophyllene and CBD — that are able to target CB2 receptors in different ways. 17

Interactions between phytocannabinoids and terpenes could produce a synergistic effect when treating pain and inflammation. This synergy increases the chances that even more research and development will continue on this plant.

What the Research Says on the ECS

Cannabis research is booming. Many large academic institutions are getting involved, including UCLA, UC Davis, University of Mississippi, and University of Illinois, just to name a few. This research is looking into every facet of the ECS, such as the effects of endogenous cannabinoids on the ECS. And the effects of phytochemical on the ECS, including THC, CBD, minor cannabinoids, and terpenes.

There is mounting evidence that all known cannabinoids can exert influence on a variety of receptors types, including opioid, 5HT3, and N-methyl-d-aspartate receptors. This suggests a role for cannabinoids in homeostatic pain modulation, and perhaps their use as effective wellness products. 18

The effectiveness of CBD in communicating with the ECS can depend on the method of administration. The administration method dictates how much CBD is absorbed into the system, also known as its bioavailability. The most bioavailable method of consuming CBD is by inhaling smoke. That is followed by sublingual tinctures. The least bioavailable method is taking a CBD capsule. When consumed this way, CBD is metabolized rapidly in the liver, undergoing extensive hepatic first-pass metabolism. 19

What Conclusions Can We Draw?

We can conclude that CBD plays a role in homeostatic modulation of nociceptive pain. And we can conclude that phytocannabinoids potentially offer some degree of relief in various pain states.20

We can also conclude that phytocannabinoids have much promise in treating various conditions. They could prove especially useful as a therapeutic adjunct in treating peripheral and central neuropathic pain. They could also help with inflammation-mediated chronic pain and blood pressure management.

However, the fact that cannabis is usually smoked as a method of administration remains a barrier to research. Another hurdle is the psychoactivity of THC. These concerns pose significant setbacks to better understanding the cannabis plant in a clinical setting.

Ideally, we could develop a non-intoxicating formulation that is administered orally and not by smoking. Luckily, full spectrum CBD oil seems to fit those requirements perfectly.

What are the Best CBD Products for Your ECS?

The FDA continues to delay regulations on CBD products. Therefore, CBD consumers must be very skeptical about the types of CBD products they buy. Many news outlets reported recently that many CBD products fail simple tests. Such as not having as much CBD as advertised, or having no CBD at all.

We can solve this problem by choosing CBD products that are certified organic by the USDA. This certification process assures consumers that products bearing the USDA organic seal are free of any contaminants. And, it also ensures truth in advertising.

Every product with a USDA organic seal must be certified by a third party. They can audit the supply chain of every ingredient to ensure compliance to the high standards of the USDA’s National Organics Program. Only USDA certified organic CBD products are guaranteed to be properly labeled. They are also guaranteed to be free of contamination.

Another way to be certain that you are choosing a safe, high quality CBD product is to look for Certificates of Analysis, or COA’s. Trustworthy companies will have a third-party laboratory test their products for pesticides. They will also test for residual solvents, microbials, potency, and more.

Cornbread Hemp is unique because they have QR codes on all of their products. Scanning the code with a smartphone takes the consumer directly to the product’s third-party lab reports. Cornbread’s CBD oils also have the USDA certified organic seal, proving their safety right away.


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