CBD & the Endocannabinoid System:

The Groundbreaking Team for Optimal Well-Being

Unless you’ve been lost in the Himalayas, chances are you’ve heard claims of CBD as the cure for almost anything.

Cannabidiol—aka CBD—has become the latest darling in the wellness scene.

More and more people are reporting benefits after taking any form of this seemingly miracle supplement. From regulating stress and mood to managing pain and fighting inflammation or insomnia, the list of benefits just goes on.

Have you wondered why CBD has the potential to be such a great source of healing? Well, the answer is the endocannabinoid system (ECS).

Let me break this down for you.

Table of Contents

What Is the Endocannabinoid System?

The endocannabinoid system (ECS) is a complex network of neurotransmitters, receptors, and enzymes placed throughout the  body that’s involved in nearly every aspect of human health.

The system is activated by cannabis compounds and, surprisingly, it’s present not only in the human body—but widespread through the animal kingdom, including mammals, birds, amphibians, fish, and even the hydra.

Although data tell us that the ECS is pretty old and evolved over 500 million years ago, chances are you never heard of it in school. Many people including your doctor may be clueless about it because it remained unknown until the 1990s.

So, unless you’re trying to understand how cannabis works in your body, you’re unlikely to hear about this powerful network.

In the beginning, experts thought the ECS was present only in the brain, but later, they found that its receptors are fully integrated into the body.

They’re present almost everywhere, from your brain to your skin, immune cells, bone tissue, fat tissue, liver, pancreas, skeletal muscle, heart, blood vessels, kidneys, and gastrointestinal tract.

In the brain, the system helps you modulate pain, memory, movement, emotion, sleep, appetite, emesis (the act of vomiting), and seizure threshold.

Outside of the brain, it regulates gut motility, metabolism, the immune system, and the reproductive system.

The Endocannabinoid System: A Breakthrough Discovery

The story begins with a plant called cannabis. Cannabis produces CBD, THC, and about other 100 chemicals known as “cannabinoids.”

Cannabinoids have the ability to activate your endocannabinoid system.

Although cannabis is one of the first plants to have been used as a medicine for mankind, breakthrough findings of how it interacts with our bodies are much more recent and date back to the last century.

The main drawback of cannabis as medicine has been its mind-altering effect. However, as the recreational use of cannabis dramatically started to increase, the psychoactive effects of this plant draw the attention of scientists.

One of them—Dr. Raphael Mechoulam—started his long-lasting relationship with cannabis, when he was a medical student in Israel. Then, cannabis was still illegal there.

Basically, he had to “break the law” to get access to the plant and start his research. No wonder he’s known as the “godfather of cannabis medicine.”

In 1963, Dr. Mechoulam and his team isolated and synthetized a non-intoxicating compound—CBD—and later in 1964, they did the same with THC, the infamous chemical that gets you high. This confirmed that not all cannabis compounds are psychoactive and that the wide range of chemicals present in this greenery are full of unique health benefits.

His investigations and posterior findings—like the first cannabinoid receptor in 1988 by doctors Allyn Howlett and William Devane—led to the major breakthrough in medical science in recent years, the endocannabinoid system, and it was aptly named in honor of this fascinating plant.

Here’s how this remarkable system works.

The Nuances of the Endocannabinoid System

Even though there’s still a lot we don’t know about the endocannabinoid system, the scientific community is studying it more and more these days.

It has become an important target in pharmacology to find new therapeutic drugs. However, hard evidence is still needed to fully understand its functioning.

Scientists know by now that this system is responsible for two vital functions.

First and foremost the ECS is a master regulator of your biology and overall well-being. It modulates pleasure, energy, pain responses and even promotes sound sleep patterns.

The second function is to keep in check the entire systems and organs present in your body to arrange the myriad functions necessary to survive and maintain your health.

When injury and disease occurs, the ECS restores balance within your body by promoting “homeostasis.”

The endocannabinoid system is a biological regulator of all the other systems in the human body.

Homeostasis & Our Quest for Wellness

Achieving wellness is a commonsense goal for anyone. Many of us are searching for balance: balance in mind and body, balance in our relationships, balance in our work, and balance in our health.

We want to feel better, and that’s why we flock to wellness practices like juice cleanses, yoga, trendy diets, meditation, self-care, nootropics—you name it.

We have an innate desire for balance, and that’s what homeostasis is all about.

homeostasis and our quest for wellness

The term “homeostasis” was first defined by the French physiologist, Claude Bernard, as the body’s ability to maintain and regulate its internal balance in an external environment that constantly changes. In short, homeostasis is that state of perfect equilibrium necessary for optimal health.

Homeostasis is successful when every part of your body is working together and they’re neither too active nor inactive. All the systems of the human body work as a team, and your well-being depends on the well-being of all these systems interacting in synergy.

Thus, if your body temperature rises, the process of homeostasis activates a mechanism—vasodilation—to deal with the issue, brain and skin work together to get you back to your average normal temperature as quickly as possible.

But if something interferes with this mechanism, like the distress caused by overwork, for instance, homeostasis might be disrupted. Your body loses its ability to self-regulate and self-repair, experiencing unpleasant symptoms such as a blood pressure rise or a headache. Continuous homeostasis disruptions lead to disease.


A healthy endocannabinoid system promotes homeostasis which ensures a healthy mind, a pleasant emotional state, and a top-notch physical life.

Three major players comprise the ECS, they work together to help you achieve homeostasis.

Let’s meet the players:

Cannabinoid Receptors (CBR)

They’re responsible for the way your body reacts to CBD, THC, and other cannabinoids.

Akin to radio antennas, the CB receptors receive chemical messages from cannabinoids and a rich repertoire of cell responses is activated.

The impact of these responses depends on where the receptor is located.

To date, we’re familiar with 2 subtypes of receptors found in the endocannabinoid system; CB1 and CB2 receptors. Each one responds differently to different cannabinoids.

It’s because the cannabinoid receptors are so broadly spread throughout the body that the EC system is able to play such a big role in promoting balance to all the eleven systems in our bodies.

There are additional cannabinoid receptors that include nuclear receptors: PPARs and TRPV1. But studies about their functions are incomplete and research is ongoing.

What do these receptors do?


They modulate the release and function of various neurotransmitters, including GABA, glutamate, dopamine, serotonin, and anandamide.
CB1 plays a key role in regulating neurotransmitters in a manner that maintains homeostasis by preventing excessive neuronal activity in the central nervous system.

By activating this receptor, scientists have found benefits for ailments like eating disorders, movement disorders, memory deficits, psychosis, and various addictions.

Nevertheless, its activation doesn’t come without risks, CB1 is a psychoactive receptor.

When THC triggers these receptors in your brain, the reward pathway is activated, and you get feelings of euphoria and intoxication. In other words, you get high.

Now there’s a catch, THC only has unpleasant effects when it binds to CB1 receptors in the brain. Outside the central nervous system, it imparts non-psychoactive but therapeutic anti-inflammatory effects.

Evidence shows that THC may also be an effective treatment for multiple maladies, including the side effects of chemotherapy.

Ever heard that the gut is our second brain? Well, there’s plenty of CB1 receptors in the gut that team up with the ones in the brain to modulate various aspects of metabolism such as food intake and energy expenditure.

When THC activates the CB1 receptors in the brain’s region that regulates hunger and satiety, you will get “the munchies” meaning appetite will be induced. On the other hand, when the receptors are blocked in this area of the brain, appetite will be reduced.

You may wonder if what you need to stop your ravenous sweet tooth is to block this receptor in your brain.

Not so fast…

Researchers found that blocking CB1 receptors in the brain is not safe. It has shown severe side effects such as anxiety, depression, sleep disorders, mood swings, headaches, nausea, vomiting, seizures, increased blood pressure, and enhanced risk of suicide.

Ouch! That’s indeed a long list of risks and probably the reason we still don’t have a safe weight loss pill that actually brings results.

Thus, scientists are wisely focusing now on blocking CB1 receptors outside the brain. In fact, CB1 inhibition in peripheral organs has shown great potential in animal models.

Scientists at the National Institutes of Health (NIH), reported enhanced insulin sensitivity in pancreas and liver cells, and also muscle loss prevention in aged population when blocking the CB1 receptors in the periphery.

Awesome, isn’t it? Now let’s meet the second receptor.


These receptors are like little soldiers that help protect your body from virus and bacteria, but their function in the immune response of the body is still unknown.

They’re also mediators of some of the anti-inflammatory actions of cannabinoids like CBD.

The activation of the CB2 receptors doesn’t have a mind-altering effect, turns out, it could counteract this effect in the CB1 receptors.

By manipulating CB2, scientists have found drugs that may have analgesic and tissue-protective effects, but the mechanism of action is still unclear. What is clear is that these drugs won’t produce a high.

Ongoing cutting-edge research suggests that the interaction between CB2 and CBD shows promising anti-inflammatory properties.

To ensure CB1 and CB2 achieve their important roles in your body proper communication is needed. The messengers that activate this communication are the cannabinoids and your body makes its own natural versions of these compounds.

Let’s meet….

The Endocannabinoids (eCBs)

Endocannabinoids are the cannabis-like molecules that your body produces. They travel from cell to cell, transporting important messages to activate the cannabinoid receptors.

Together receptors and messengers unleash a series of reactions throughout the endocannabinoid system. These reactions establish the communication between the mind and the body, bringing vital functions back to balance.

Like dopamine and serotonin, endocannabinoids can perform as neurotransmitters too, switching your nerves on and off.

The functions associated with eCBs are chill, eat, sleep, forget, and protect.

Endocannabinoids are non-water-soluble due to their fatty-based nature. This particularity makes them hard to transport within the body and this is why your body tends to manufacture them on-site. Specific eCBs are created to target specifically selected areas.

They’re created on-demand, in other words, they’re synthesized only when your body signals that they’re required.

They’re also short-lived, once they have done their job and information is delivered to the proper cell, specific enzymes quickly break them down, so they don’t keep stimulating your ECS indefinitely.

When your body doesn’t produce enough eCBs to interact with the cannabinoid receptors, communication is interrupted and you’re more likely to develop symptoms and conditions, particularly those related to the immune system and inflammation.

Some of the ailments that have been associated with eCBs deficiency are:

  • Depression
  • Anxiety
  • Irritable Bowel Syndrome
  • Attention-Deficit/Hyperactive Disorder (ADHD)
  • Sleep Disorders
  • Fibromyalgia
  • Parkinson’s
  • Multiple Sclerosis
  • Chronic Stress
  • Migraine
  • Obesity

The two major endocannabinoids are anandamide and 2-arachidonoylglycerol.


Anandamide is also known as the “bliss molecule” because of its mood-enhancing effect. Discovered in 1992 by the godfather of cannabis medicine, Dr. Mechoulam.

Your amazing body harnesses its own internal chemistry to produce feel-good chemicals like anandamide. AEA is a stress-responsive endocannabinoid that plays a vital role in the generation of pleasure and motivation in your brain. Craving sweets? Well, anandamide is the culprit.

It turns out that anandamide has a chemical structure similar to THC, and can also stimulate the CB1 receptors, even though not as “strongly” as THC does.

A hint of why cannabis makes us high, but anandamide doesn’t.

Ongoing studies are exploring the role of AEA in human conditions and behaviors like eating, pain relief, sleep patterns, pregnancy, and memory.



This mouthful—that I can barely pronounce—stands for the second endocannabinoid found by Dr. Mechoulam in 1994. It triggers both CB1 and CB2 receptors.

It’s known as the “workhorse endocannabinoid.” Your body releases 2-AG to regulate a variety of neural processes like appetite, immune system functions, and pain management.

2-AG is abundant in mother’s milk and is purported to be essential in stimulating newborns appetite and also helps to calm and relax the baby.

Something interesting to add here is that 2-AG has been linked with the state of totally relaxed bliss you have after orgasm, hah!

There’s also evidence that it may play a role in the inhibition of cancer cell proliferation.

All right, last but not least:

Regulatory Enzymes

Enzymes are the clean-up service of the system. They’re responsible for synthetizing and destroying endocannabinoids, rendering them inactive.

Once eCBs have been used, they’re broken down and not available to keep stimulating the ECS for longer than intended. There are 2 of them:

  • Fatty Acid Amide Hydrolase (FAAH) is the enzyme that breaks down anandamide in the nervous system.
  • Monoacylglycerol Lipase (MAGL) is a key enzyme that breaks down 2-AG.

Researchers use enzymes inhibitors to manipulate the CB receptors and find new medicines.

Now the juicy stuff …

How CBD Interacts with the Endocannabinoid System

There’s a misconception that CBD blocks the cannabinoid receptors in your brain. This is not accurate, CBD has a very weak affinity for these receptors, so it’s not able to block them.

On the bright side, CBD works backstage to prevent them to get overstimulated particularly the CB1 receptors and enhance the communication between CB2 and the endocannabinoids.

These actions within the body’s endocannabinoid system allow it to function better and more efficiently.

Let’s break this down.

Facts Matter: 15 CBD Myths Debunked


Technically speaking, CBD and THC are both psychoactive molecules because they have the ability to affect your brain, but CBD should be labeled as “non-intoxicating” since it doesn’t get you high.

THC makes us high because it has a strong affinity for the CB1 receptor, which is a psychoactive receptor. But cannabidiol doesn’t interact with the cannabinoid receptors… at least not in the same fashion.

It turns out that CBD tones down the activity of the CB1 receptors by activating other channels—the TRPV channels—which are involved in regulating pain, body temperature, and inflammation.

CBD’s ability to dampen the psychoactive action of CB1 explains one of its more interesting properties….


As we already addressed, cannabidiol prevents the overstimulation of the CB1 receptors, this way it also lowers the ceiling on how high THC can get you. Overstimulated CB1 receptors are associated with psychosis and schizophrenia.

A study conducted by Dr. Daniele Piomelli, professor of pharmacology at the University of California-Irvine, found that CBD was as effective as major tranquilizers prescribed to treat schizophrenia, but without the typical side effects of these anti-psychotic drugs.


CBD and CB2 receptors work beautifully together. Emerging data suggest that CBD enhances the bioavailability of endocannabinoids anandamide and 2-AG, which boosts cannabinoid receptor signaling throughout the body.

Meaning CBD induces the CB2 receptors to use more of these endocannabinoids when they’re present in your bloodstream.

Since the CB2 receptors regulate inflammation and immune cell activity, CBD’s action can help reduce pain, fight inflammation, and improve your body’s ability to fight off infections.

In this light, CBD not only inhibits CB1 receptors, but it also can amplify CB2 at the same time.

This is kind of a big deal because ailments like diabetes, heart disease, obesity, and other diet-related disorders are associated with overactivity of the CB1 receptors plus and inadequate CB2 stimulation. Therefore, cannabidiol is a well-suited alternative to treat these conditions.

But CBD is even more versatile. It not only impacts your cannabinoid receptors. CBD goes the extra mile to act on other receptors within the brain to achieve homeostasis.

Experts believe CBD interacts with the serotonin receptors, pain receptors, gene expression receptors and also with some specific enzymes. These interactions lead to a number of potential benefits, such as:


Inflammation is your natural bodyguard, it protects your body from infections, diseases, and injuries.

But it turns into a silent killer when it becomes chronic. In recent years, science has found a link between chronic inflammation and a range of health conditions like cancer, heart disease, arthritis, Crohn’s Disease, and irritable bowel syndrome IBS.

Preclinical studies hold promise of the anti-inflammatory benefits of CBD. When inflammation is high in your body, your immune system becomes the enemy.

Immune cells and infection-fighting cytokines increase, and your overall health suffers. CBD modulates CB2 receptors which regulate cytokines’ production.

Scientists have also found that CBD stimulates the PPARs channels. They’re a family of receptors that send signals to our DNA to change its genes expression. In short, PPARs can turn your genes on and off.

The effects of CBD particularly on the PPARy receptors has been linked to its anti-inflammatory and neuroprotective actions.


Even though CBD shows a weak affinity for the cannabinoid ligands, studies indicate that it strongly acts on receptors out of the ECS. These include the serotonin 5-HT1A receptor, which can help regulate sleep, mood, anxiety, and pain.



The FDA recently approved the drug, Epidiolex, with CBD as the main ingredient to treat seizures on children suffering from rare forms of epilepsy which couldn’t be successfully treated with traditional anti-seizure medications.

Scientists are currently hunting for a “hidden” brain receptor that may explain the anticonvulsant mechanism of action of CBD.


Research has proven that cannabidiol increases the amount of endocannabinoids in the body. It appears that CBD binds to fatty acid-binding proteins (FABPs) and reduce endocannabinoids metabolism. As a result, more eCBs will be circulating in your bloodstream.

Higher levels of eCBs in the bloodstream result in greater cannabinoid receptors activity, leading to bigger chances of a more efficient ECS that supports and maintain your overall health.

Other studies suggest that CBD interferes with the enzyme FAAH, responsible for breaking down and degrading anandamide.


The list of potential CBD benefits keeps growing as more lab research shows its antioxidant properties. Free radicals are atoms with orphan electrons that look for other atoms to bond to. They’re unstable and when they accumulate too much, they lead to a process called oxidative stress.                   

Oxidative stress is linked to a range of diseases and aging symptoms, such as grey hair and wrinkles. Ugh!

Antioxidants, on the other hand, are chemicals that can slow down the oxidative stress process. They donate electrons to the lonely electrons in free radicals, making them stable and fighting their harmful effects.

Research shows that cannabinoids, especially CBD, are potent antioxidants that can reduce the number of free radicals and enhance cellular health.

Ways to Tune Your Endocannabinoid System

Many reasons that are beyond our control can disrupt the endocannabinoid systems. The human body and how it works is still a wonder.

However, you’re not powerless. Research shows that there are natural ways to restore a healthy balance in your body. One of the first steps you can take is to figure out where the imbalance is coming from.

Some of us might have a deficiency of endocannabinoids production while others may be suffering the overwhelm of an overstimulated system. The balance in our ECS is a result of how we live, how we move, how we eat, and how we think.

Although CBD has shown amazing properties to make your ECS a well-operating system, it’s not the only solution available. There are other natural ways that you would like to try. So, here’s the list.


Not only CBD but other phytocannabinoids like THC, CBN and CBG can help stimulate your ECS to work properly and provide your body with enough cannabinoids to achieve homeostasis.

Each phytocannabinoid interacts with the ECS in a slightly different way. you can find phytocannabinoids in other plants such as maca, ginger, black pepper, nutmeg, truffles, hops, and even in dark chocolate.


There’s no doubt that the gut is our second brain. Emerging research shows that the endocannabinoid system and the gut microbiome are connected. We now know that the gut microbiome impacts mental health because it communicates directly with our brain through the gut-brain axis. 

Studies on mice models that were supplemented with a specific probiotic showed an increase in the expression of CB2 receptors, that may help reduce stress and anxiety.


Endurance exercise has been shown to activate the endocannabinoid system. If you ever experienced the “runners high,” you know that there are natural substances in your body that can boost your mood naturally.

For decades experts believed the euphoric spark you feel after aerobic exercise was powered by endorphins. But new data suggest that it’s the result of endocannabinoids circulating in your bloodstream, specifically anandamide.

However, if running is not your thing, worry not, the benefit is not only limited to cardio bunnies because other physical activities can also support the ECS.

Exercise, in general, helps to maintain a healthy weight and manage stress levels, both of which should help keep the endocannabinoid system in balance. A brisk 30 minutes’ walk can make you burn 150 calories and help you feel calmed and relaxed.


Omegas are essential fats required for health. They play a vital role in the normal functioning of your brain, cardiovascular health, nervous system, and well-being in general. Without them, your body can’t function properly and that’s why they are termed as essential.

Essential fatty acids such as omega 6 and 3 are required to produce endocannabinoids in your body.

However, your body doesn’t produce them, you have to get essential fatty acids from food. Sadly, our western diets that have an excess of omega 6, lack badly the optimal levels of omega 3 required.

This imbalance down-regulate the production of eCBS and therefore throws off the well-functioning of your endocannabinoid system.

There’s a connection between low omega-3 fatty acid intake and poor endocannabinoid function that leads to depressed mood, hostility, and impulsive behavior.

Poor memory and cognitive decline with aging are also associated with low levels of omega-3 fatty acids.

There’s a variety of foods rich in omega 3, that you can add to your diet to support a well-balanced ECS, such as:

  • Fish and seafood like salmon, tuna, herring, and sardines.
  • Nuts and seeds like flaxseed, chia and hemp seeds, and walnuts.
  • You may also benefit from taking omega-3 supplements, like fish or krill oil.


Dark chocolate is a rich source of antioxidants, minerals, and more than 300 compounds.

Surprisingly, chocolate contains a number of psychoactive ingredients, including anandamide, the feel-good endocannabinoid which may be the reason why chocolate is so craveable.

It also contains phenylethylamine, a neuromodulator that is believed to be important for regulating mood.

To top it off, dark chocolate also has compounds that slow down the degradation of anandamide, and by now, you already know that the more anandamide in your body, the more chances to have a well-balanced ECS.

Final Thoughts

The endocannabinoid system is a breakthrough discovery for medical science, but the understanding of how it works within the body is at its infancy. This system was discovered only 30 years ago, and scientists are still figuring out its nuances.

Even though CBD is the in-thing right now, there’s clearly a knowledge gap on how to supplement with this plant-based cannabinoid to enhance your well-being.

So, getting all the information you can, being aware of the pros and cons, and choosing a high-quality product to boost your body’s performance is mandatory in your quest for wellness.

The jury is out. I presented you some of the CBD’s potential benefits that are backed up by science. However, all these scientific papers are still not in the stage to support generalized conclusions. CBD research has a long way to go.

I’ve been using CBD for the last 3 years and I believe it has positively enhanced my overall quality of life, but don’t take my word on it, try it for yourself that’s the only way to know what CBD can do for your health.

Always go for lab-tested, organic non-GMO products. Remember that CBD is not a one-size-fits-all solution. Expect trial and error when trying it for the first time.

It’s always a good idea to speak to your doctor before supplementing with CBD, as it may interact with other drugs. Rest assured, I wish you success in your journey.

To your well-being.

Quick Wrap-Up

  • Just like you, your body is in a constant quest for balance. The most important tool your body has to achieve this balance is your endocannabinoid system.
  • This system doesn’t only respond to the endocannabinoids that your body produce. It also responds to external cannabinoids like CBD and THC.
  • Your ECS can be thrown out of balance very easily. Stress, diet, and lifestyle may be taking a toll on it. CBD promotes well-being by boosting the production of endocannabinoids in your body.
  • It also interacts in different ways with the cannabinoid receptors as well as with other receptors in the body which explains the wide range of diverse ailments that cannabidiol may treat.
  • Adding CBD, exercise, omega-3 fatty acids, dark chocolate, and probiotics to your daily regimen may support and restore your ECS.

Are you considering including CBD in your daily wellness routine, or are you already feeling its benefits? Your experiences matter! Feel free to share them below. Have questions? Ask away!