THE ENDOCANNABINOID SYSTEM

Did you know that your body is producing its own internalized form of CBD — right now? Further, did you know that this internal compound is part of the largest receptor system in the human body? Sometimes, truth is stranger than fiction…and in this case, both statements are true!

Your body makes endo-cannabinoids at virtually all times, in virtually all parts of the body. And though these substances aren’t completely identical to CBD, they function so similar to it that scientists consider them to be endogenous analogs (aka, internal versions).

These endocannabinoids (eCB) play a major role in the human Endocannabinoid System (or ECS for short). Together with endocannabinoid receptors and endocannabinoid enzymes, eCB’s comprise the largest and most extensive receptor system known to science.

A SYSTEM OF LOCKS AND KEYS

As we said, there are three major components to the endocannabinoid system. Let’s take a closer look!

Endocannabinoids (eCBs). Endocannabinoids are made of fatty acids (that’s part of why omega 3’s are so important) and produced in an on-demand nature. In general, high eCB levels are better than low ones.  The most important endocannabinoids to know about are anandamide and 2-AG. 

Anandamide was the first endocannabinoid to be discovered. Nicknamed after the Sanskrit word for “bliss”, anandamide’s scientific name is arachidonoylethanolamine. For obvious reasons its nickname stuck! Research has uncovered many of anandamide’s health benefits: it has the ability to reduce anxiety and depression, promote flexible thought, and even slow the growth of cancer.

2-AG is the other primary endocannabinoid; this one’s much more active in the brain than anandamide is — up to 1,000 times higher, in fact!  2-AG directly agonizes (or activates) endocannabinoid receptors, which makes it very potent. The endocannabinoid has also demonstrated impressive anti-cancer qualities. Overall, both 2-AG and anandamide work to lower and limit stress

Cannabinoid Receptors. There are two major types of cannabinoid receptors: CB1 and CB2. CB1 operates mostly within the brain, where it’s the most prevalent receptor in its class. CB1 can also be found throughout the CNS (central nervous system), immune system, and GI tract. It’s noticeably absent from the brain stem, though, which is a good thing because many substances that activate this sensitive area can also be overdosed on. But not CBD!

CB2 receptors operate mostly in the body, especially within the peripheral nervous system and the vital organs. Just keep in mind that these distinctions aren’t that exact. In reality, both types of cannabinoid receptors can be found to various degrees everywhere

Think of cannabinoid receptors as locks that hold the keys to balance and health…locks that can only be unlocked by endocannabinoids (the keys).  Depending on the particular cannabinoid/receptor combination, different locks and keys fit together differently. An endocannabinoid may directly activate its receptor, but it could also potentially de-activate it. As always, the human body is amazingly complex, yet also seems to always know what it needs.

Endocannabinoid Enzymes. Once again, there are two types: those that form eCB’s, and those that break them down. A third functional group called FABP’s also helps control endocannabinoid levels.

All of these enzymatic reactions are important, because endocannabinoids levels sometimes need to fluctuate in order to meet the body’s needs. In some cases, though, CBD can actually shut down breakdown enzymes and allow greater endocannabinoid buildup. We’ll look more at this phenomena soon.

THE ENDOCANNABINOID SYSTEM IS HERE FOR A REASON

We humans aren’t the only ones with an endocannabinoid system. All species with a vertebrate also have their own endocannabinoid system, something that hints to the ECS being very, very old. It also points to the system’s importance — it must’ve been evolutionarily conserved for a good reason. 

In a word, that reason is homeostasis. In three words, full-body balance. The endocannabinoid system helps regulate perception, pleasure, pain, sleep, appetite, reproduction, immune function, memory, and much more. As neurologist Dr. Ethan Russo says, “there is hardly any physiological process untouched by the ECS to some degree.”

As amazing as the ECS is, it’s not bulletproof. Like anything else in the body, its reserves can get exhausted by the chronic stress of modern living. When endocannabinoid supply is low, disease tends to result.

This concept, which Dr. Russo coined “clinical endocannabinoid deficiency syndrome” or CECDS, was highly controversial when he first proposed it in 2004. In a pivotal paper on the topic, Dr. Russo claimed that low endocannabinoid levels are at the root of many common diseases, especially those that tend to respond poorly to treatment.

Yet today the theory is gaining credence and popularity in the medical community. After all, those with chronic migraines, fibromyalgia, and IBS almost always report amazing results from CBD. Take these people to the lab, and an analyzation of their eCB levels reveals that things are indeed running low. In summary, CECDS simply makes sense. How else could one compound appear to address so many different disorders and illnesses?

High endocannabinoid levels, on the other hand, are almost always representative of good health. When the ECS is running smoothly, it’s able to keep the areas it operates in (aka, the entire body!) balanced. Scientists aptly call the system a homeostatic regulator. A person with good endocannabinoid tone would likely be as healthy as it gets, with no digestive issues, mood disorders, or sleep problems.

But as you know none of us live in a perfect world — and for that reason, we couldn’t be any more thankful for CBD. In this plant compound, nature has provided us the perfect antidote for the stressors of daily life. That’s because CBD holistically boosts endocannabinoid levels and, over time, can restore the body to a place where it can better heal itself.

HOW DOES CBD HELP?

This is where things get complex! CBD appears to strengthen the ECS in three main ways:

It inhibits the enzymes and proteins that normally break endocannabinoids down. Several studies have shown that only a few doses of CBD are enough to slow down the FAAH enzyme, which normally breaks down anandamide. It also seems to prevent related compounds called FABP’s from doing the same thing.

Normally, these same enzymes keep things in perfect balance…but for whatever reason, in times of disease they don’t always seem to be self-correcting. That’s where Cannabidiol comes in. By preventing anandamide’s breakdown, CBD allows levels of this endocannabinoid to slowly build up. That means more happiness, less depression, and more.

It sensitizes endocannabinoid receptors to their signals. Based on what you’ve read so far, you might think that high endocannabinoid levels are always a good thing…but that’s not (always) the case. In some instances, a diet too high in processed fats or inflammatory foods may push endocannabinoid production over the edge.

When this happens, endocannabinoid receptors respond by closing themselves off and shutting down. CBD counteracts this by encouraging receptors to stay open and receive the right messages. In some cases, CBD’s even been shown to help CB1 and CB2 join forces with serotonin receptors, in the process lifting mood and strengthening the nervous system.

It interacts with receptors from related regulatory systems. Though it is a cannabinoid, CBD isn’t confined to the endocannabinoid system alone. It also gently influences receptor binding sites for serotonin (as mentioned above), dopamine and endorphins, GABA, TRP channels, and nuclear receptors.

Why so many systems? Most likely because CBD’s size and shape make it perfect for interacting with many different G-coupled protein receptors (GPCR’s) — not just the endocannabinoid variety. Though that term sounds complex, GPCR’s are just a collection of receptors classified by how they physically send and recieve messages. And CBD is able to send messages to many of them without getting in the way of normal function.

It gently binds with CB2 receptors. CBD only has a low affinity (think magnetism) for CB2, but that doesn’t stop it from taking action in times of need. CBD may bind to CB2 receptors in the digestive lining to help relieve IBS and ‘leaky gut’ or in the liver to increase insulin sensitivity.

Interestingly enough, CB2 receptors have shown an ability to materialize wherever most needed in the body. If one’s health is damaged specifically in one or two areas, you can bet that the endocannabinoid system will sense it…and that CB2 density will be elevated! Thanks to this adaptation it’s relatively easy for cannabinoids like CBD to ‘zoom in’ and target the areas where they’re needed most.

Overall, you can thank the CBD /CB2 receptor combo for much of the compound’s power. Thanks to the endocannabinoid system, CBD is able to reduce inflammation, lower stress, and increase our ability as human beings to adapt and overcome. Not bad for one small plant molecule.

ADDITIONAL STUDIES

A 2009 study discovered that CB2 receptors have the therapeutic potential to address conditions that demonstrate hyper-inflammation, like ALS, AIDS, multiple sclerosis, and Alzheimer’s disease.

A 2014 study discovered that CB2 receptors play a part in modulating dopamine activity in the area of the brain responsible for reward and addition, known as the ventral tegmental.  The study found that by activating CB2 receptors, cocaine-addicted mice administered a decreased amount of cocaine to themselves.  This supports the idea that the activation of CB2 receptors could provide effective therapy against drug and opioid addiction.

A 2016 study showed that CB2 is found primarily in immune tissues and is expressed in most immune cell types.  Several animal models have shown that the removal of CB2 caused an exacerbated inflammatory phenotype.  These models also showed the administration of CB2 agonists to slow the progression of some diseases — in addition to reducing inflammation.  This study concluded that CB2 activation by cannabinoids usually decreases the activation of inflammatory cells.

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