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The Endocannabinoid System and CBD

Posted by Dr. Leslie Mudd, PharmD on Jul 14th 2020

The Endocannabinoid System and CBD

The Endogenous Cannabinoid System, or the Endocannabinoid System is one of the most amazing systems in the human body. Since the endocannabinoid system (ECS) was discovered so recently, almost 30 years ago, we don’t have much data about how it works. But, we do know that cannabidiol (CBD) from cannabis interacts with the ECS in amazing ways that can play a role in many benefits for human health. By reading this article, you will learn about CBD and the ECS, and how to choose the best CBD oil to get benefits to your ECS.

What is CBD?

CBD is short for “cannabidiol.” It is one of at least 150 different known cannabinoids present in Cannabis sativa. Each cannabinoid plays a role in communicating with the endocannabinoid system (ECS). "Hemp" is different from "marijuana". Federally legal hemp is defined as cannabis which contains no more than 0.3% tetrahydrocannabinol (THC) by dry weight. Marijuana with high levels of THC content are federally prohibited, and only permitted in states with specific state laws allowing medical or recreational marijuana use. When we talk about CBD and CBD products, we are usually referring to federally legal hemp-derived CBD containing less than 0.3% THC.

CBD is a great option for those who want to experience the benefits of cannabis without the psychoactive effects of marijuana. CBD does not get you high like THC does. And CBD tends to have few if any side effects. If any side effects occur from CBD, it's either from taking too much of it, a cannabis allergy, or from drug interactions. CBD is generally regarded to be a safe supplement due to the low risk of negative side effects.

How is CBD Oil Made?

CBD oil is made by extracting cannabinoid components from hemp plants, often using a solvent based extraction process. Then the extract is blended with a carrier oil like MCT coconut oil. CBD can be used in many forms and applications like oils, capsules, topicals, and edibles.

CBD legalization has taken the American health industry by force. Nearly every natural health food store has a CBD case near their wellness products, and CBD shops have sprung up everywhere. You can even find CBD oil at gas stations! (We don't recommend gas station CBD though, it's usually low quality.) So how exactly does CBD help people manage their aches & pains and help them navigate stress? That answer may lie in studies pertaining to the endocannabinoid system.

What is the Endocannabinoid System?

The human endocannabinoid system (ECS) networks a series of receptors located throughout the body in order to maintain homeostasis and immune system modulation.1 The term "homeostasis" refers to the maintenance of keeping your body's internal environment stable despite what is going on externally. The way the body maintains its internal body temperature is a great example of how homeostasis works. If you are too hot, the body responds by sweating. If you are too cold, the body generates heat by shivering. The body reacts to an imbalance by taking action to bring the internal environment back to balance.

We are still learning all of the ways that the ECS helps the body maintain homeostasis. Since cannabinoid receptors are found throughout the body and its other systems, it seems that there are many body functions that could potentially be effected by the ECS. But researchers are focusing on how this special receptor system may help with inflammation control and stress response.

The ECS works by binding with cannabinoids, both endogenous (produced by the body) and exogenous (produced outside the body). Cannabinoids produced by the body are called endogenous cannabinoids, or “endocannabinoids”, ones produced by plants are called “phytocannabinoids.”

The ECS has been described as “an ancient lipid signaling network which in mammals modulate neuronal functions [and] inflammatory processes… The cannabinoid 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 endocannabinoid system to understand how CBD works in our bodies.

Cannabis and the Endocannabinoid System

The word “cannabinoid” comes from the Cannabis sativa 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 cannabinoid receptors (we will detail them below). Cannabinoids bind to these CB receptors to help the body bring systems back into balance. This system of 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. They discovered that the ECS is integral to all sorts of homeostatic functions, such as the modulation of pain signals.

Our research into endocannabinoids is still incomplete. We don’t know if we have identified all the cannabinoids produced inside the body. 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 dried marijuana plant flowers) is unconventional in a clinical setting. This has also proved a hurdle in research.

But there’s more to cannabis 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 cannabidiol (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 endocannabinoid system 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 endocannabinoid system. 4

How Does the Endocannabinoid System Work?

Scientists are still trying to understand the wide ranging effects of the ECS. Its cannabinoid receptors are found along the central nervous system. CB receptors are also found in high concentrations in brain cells, the immune system, and in the digestive system. They are found in lesser concentrations all throughout the other areas of 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 receptors. CB1 receptors appear concentrated in the central nervous system, while CB2 receptors can be found in peripheral nervous system throughout the body. These cannabinoid 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 CB1 receptors doesn’t appear in the entire brain, only in certain parts. For instance, CB1 can be found in the hippocampus and associational cortical regions, the cerebellum, and the basal ganglia. But CB1 receptors are not found in the brain stem, medulla, or thalamus- areas of the brain that control your heart rate and breathing. This may be the reason why there is no risk of fatal CBD overdose.

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 side effects from THC, such as dysphoria and paranoia.

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 homeostatic modulations, immune system function.8 Evidence shows that CB2 receptor activation reduces 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 human 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 recreational cannabis users 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 signaling seems to come from cannabidiol’s agonist activity at CB2 receptors. 13 The more studies done with CBD on cannabinoid receptors, the better our understanding will be of this sensational chemical compound.

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 sensation 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 Endocannabinoid System

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 aches & pains. 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

Research Set-Backs

Research supports the idea that CBD plays a role in homeostatic modulation of the body, and that phytocannabinoids could potentially have significant therapeutic advantages.20

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 hemp 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.

Finding Safe CBD Products

The FDA continues to delay regulations on CBD products. Therefore, 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- yes there is fake CBD out there!

USDA Organic

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.

COA's from a Third Party Lab

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. This prevents companies from altering or tampering with their test results. Thorough labs will also test for residual solvents, microbials, potency, and more.

Source Domestically

Did you know that many major CBD companies source their hemp from overseas? It is more difficult to ensure the quality and safety of hemp that was grown in other countries like Europe and China. Cannabis is a bioaccumulator, meaning that it absorbs all the of toxins from its environment. Great for the soil, not great for your CBD oil. There is greater risk of contamination when sourcing and shipping hemp from overseas.

Domestically sourced hemp is always going to be fresher than the globetrotting material. And there are more regulations on hemp production here in America than there may be elsewhere. Make sure you know the source of the hemp that your CBD oil is made from. The best CBD brands will tell you exactly where they source their hemp from. Look for United States sourcing for fresher, and safer, CBD products.  

Choose Quality

The general rule of thumb when it comes to shopping for CBD, is to look for quality- not value. A high end health food store is more likely to carry products that have been vetted for authenticity and safety by supplement buyers. Whereas a cheaper bottle from a gas station may be less than fully researched, and could even be fake. There is one brand that chooses the best option for every step of the CBD production process, and they are making sure that their customers are getting safe, potent, top of the line CBD products: Cornbread Hemp.

Why Choose Cornbread Hemp

Cornbread Hemp is a family owned company that makes their CBD oil from organic hemp grown in Kentucky. Only the most potent hemp flowers are selected for use in making the extract. Stems and leaves have little CBD content, so they are excluded from Cornbread Hemp's raw material.

Most companies use the supercritical CO2 extraction process to pull a full spectrum of cannabinoids from hemp. While this process produces a relatively safe and clean extract, it is a harsh method that leaves the end product tasting bitter. Cornbread Hemp chooses to use the organic sugarcane ethanol method in small batches for extraction instead. This method is far more gentle, and the end product is smooth tasting with no need for added flavors or sweeteners.

Cornbread Hemp knows that full spectrum CBD is the best for achieving the entourage effect on the endocannabinoid system, so all of Cornbread Hemp CBD products have the full range of cannabinoids present in hemp. This includes the federally legal amount of less than 0.3% THC, so all the compounds can work with each other for maximum benefits.

For their CBD products, Cornbread Hemp chooses to use organic MCT coconut oil as a carrier for their portent flower-only extract. MCT molecules are small enough to absorb easily through cell membranes, making it the perfect vehicle to increase CBD bioavailability.

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 Hemp’s CBD oils also have the USDA certified organic seal, proving their safety right away.

For high-quality organic CBD oil that you can trust, choose Cornbread Hemp.

Final Thoughts on CBD and the ECS

Cannabis has been used medicinally by humans since ancient times, but there has never been the research to back it up as a beneficial plant- until recently. Scientists now know that CBD from cannabis influences a part of our anatomy made up of cannabinoid receptors, and that network is the human endocannabinoid system. These receptors are found throughout the body and can impact it in many meaningful ways when it comes to overall health and wellness.

We hope this blog post provided you with the foundation to understand how CBD affects the endogenous cannabinoid system. And we also hope we showed you how CBD has the potential to positively affect many wellness issues we encounter in our daily lives.

All rights reserved. The statements made regarding these products have not been evaluated by the Food and Drug Administration. The efficacy of these products has not been confirmed by FDA-approved research. These products are not intended to diagnose, treat, cure or prevent any disease. All information presented here is not meant as a substitute for or alternative to information from health care practitioners. Please consult your health care professional about potential interactions or other possible complications before using any product.

Cornbread Hemp works with suppliers who guarantee a less than or equal to 0.3% THC content. With these trace amounts of THC, it is possible that users may fail a drug test. Cornbread Hemp does not take any responsibility in the instance a customer fails a drug test while using these products.



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