The Endocannabinoid System: Here’s How it Keeps You Healthy and Happy
In order to consume medical cannabis in a responsible and efficient manner, you should completely understand what exactly goes on in our body when we introduce to it the active molecules from the cannabis plant.
The way these cannabis-derived compounds interact with our organism is really astonishing.
The endocannabinoid system consists of cellular receptors that are found in very large amounts all throughout the body, and the endocannabinoids—our internal chemical compounds that entice these endocannabinoid receptors.
Because this is such a complicated topic, wrapping your head around everything requires some patience and dedication.
However, fathoming the endocannabinoid system is really rewarding and extremely beneficial to anyone looking to consume cannabis for healing purposes.
It should be taken into consideration that the science of cannabis still has a long way to go, and because of this there are some blanks waiting to be filled.
The almost century-long worldwide illegality of this plant should be held accountable for this limited body of research, and the reasons that led to the banning of cannabis are also quite sketchy.
Nonetheless, the available collection of scientific works confirms that consuming cannabis-derived cannabinoids compels our body to produce more (endo)cannabinoid receptors, but also to create additional quantities of our internal endocannabinoids.
Both endocannabinoids from our body, and the cannabinoids from the cannabis plant activate cell-receptors that causes that individual cell to react in a certain way, and this reaction is dependent on the type of cell that was activated through these receptors, but also on the condition our body is struggling with at that time.
This may sound like science fiction, but we’re slowly going to go through the science behind the endocannabinoids system, making all this much more understandable.
Let’s check out the most notable aspects of this topic, which we’ll cover in great depth, one at a time.
- What exactly is the endocannabinoid system, what is its purpose, and when was it discovered?
- Main types of cellular receptors within the endocannabinoid system
- Main types of endocannabinoids / how they influence the endocannabinoid system
- Endocannabinoid system deficiency
Role of the endocannabinoid system
First, the endocannabinoid system (also known as the ECS) is a vast “network” which is comprised out of:
- Cellular cannabinoid receptors. These receptors are located on the membranes of many different cells that are found across our body.
- Endocannabinoids, the active signaling molecules produced by our body. They are structurally very similar to active compounds found in cannabis. These internal cannabinoids (just like the ones from cannabis) activate the cannabinoid receptors, and by doing this trigger a specific response from a cell.
- Different enzymes that are responsible for the creation (synthesis) and later the degradation of these compounds.
What’s truly amazing about the endocannabinoid system is that the cells which express these specialized (endo)cannabinoid receptors are located in all of the most important parts of our body, including:
- The central nervous system (brain, spinal cord)
- All vital organs
- The reproductive organs
- Various glands
- The immune system
- Gastrointestinal tract
- Connective tissues
So, we have this extremely widespread network of cell-receptors that react to endocannabinoids and cannabinoids, but what the function of this system?
The sole purpose of the ECS is to maintain balance within an organism.
This is achieved by performing different tasks within an individual cell, because depending on what type of cell it is (nerve cells, immune cells, skin cells, muscle cells, secretory cells and so forth), the precise mechanism of action of that specific cell will be different.
The way a specific cell reacts when a endocannabinoid (or a cannabinoid) activates its receptor is also dependent on the type of condition that an organism is afflicted with.
This entails that the ECS is very adaptive and can trigger an extremely wide range of biological responses inside of a single cell, depending on what exactly is wrong at that given time.
In an ideal situation, where all the systems of the body including the circulatory, digestive, endocrine, integumentary / exocrine, lymphatic / immune, muscular, nervous, urinary / excretory, reproductive, respiratory and skeletal system function optimally, this perfect functioning of an organism is called the homeostasis, which can be also understood as a dynamic state of equilibrium.
The endocannabinoid system is a primary “instrument” in charge of maintaining homeostasis, and this is why the cells of all these different systems and tissues have (endo)cannabinoid receptors.
In a nutshell, the endocannabinoid system oversees maintaining health on a cellular level in every of system of the body, vigilantly reacting and adapting to the continuous changes our body encounters.
Unfortunately, the ECS does not function properly in everyone, and this malfunction is associated with the body’s inability to heal itself optimally.
Even though the precise causes of ECS malfunction remain elusive, it is hypothesized that numerous different factors including genetics, diet, lack of exercise, various pollutants and stress are all responsible for an insufficiently effective endocannabinoid system.
An inactive ECS can also be responsible for “helping” some conditions and diseases to occur, but we’ll get to all of that later.
Endocannabinoid system discovery
Uncovering how the cannabinoids from cannabis, and our own internal endocannabinoids stimulate the cellular receptors across our body was not a simple task.
Over the course of history, numerous cultures have been using cannabis for medicinal reasons.
During the 19th century cannabis-derived products were also used for health-related purposes across Europe and the US because of the pioneer work of a doctor from Ireland named William O’Shaughnessy and a French scientist Jacques-Joseph Moreau.
As the science of chemistry wasn’t fully developed, they only understood that cannabis brings relief for numerous conditions, without comprehending how the healing actually occurs.
Let’s briefly check out the precise timeline of scientific discoveries in the field of cannabis:
- 1895, the first cannabis-based compound named cannabinol (CBN) was isolated
- 1930, the precise chemical structure of cannabinol (CBN) was mapped
- 1940, the second cannabis-based compound cannabidiol (CBD) was isolated
- 1963, the precise chemical structure of cannabidiol (CBD) was mapped
- 1964, the psychoactive tetrahydrocannabinol (THC) was isolated
- 1988, the cannabinoid receptors were first located
- 1990, a cannabinoid receptor was first cloned
- 1993, internal endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) were first identified
As you can see, discoveries that happened in the last three decades include the identification of both the cannabinoid receptors and the endocannabinoids, and these discoveries are absolutely crucial for understanding how the endocannabinoid system functions, but also how the cannabinoids from the cannabis plant affect and influence this system.
Through all these years numerous scientists gave their contributions to help uncover the secrets of cannabis and the ECS, but the person who improved the science behind cannabis the most is Dr. Raphael Mechoulam, a famed Israeli organic chemist and a professor of medicinal chemistry in Jerusalem.
He was involved in mapping the structure of CBD in 1963, and one year later he and his team identified and isolated THC. During the 90’s he also participated in the discovery of the body’s own endocannabinoids anandamide and 2-AG.
You can learn more about his magnificent work in our article on THC.
The ECS was actually discovered by accident sort to speak.
In the 1980’s researchers were trying to uncover how cannabis (more precisely THC) induces the psychoactive “high”, and found that certain cells in our body have specific cellular receptors, in which THC fitted perfectly.
Researchers theorized that our body must produce its own endogenous compounds that are structurally similar to THC, and after several years of research (more precisely in 1993), anandamide and 2-AG were first identified.
By discovering the (endo)cannabinoid receptors and internal endocannabinoids, scientists have confirmed the existence of a previously unknown physiological system.
We now know that the ECS has an incredibly beneficial influence on practically every other system in our body, and functions as a tool for healing, but also for maintaining optimal health.
Before we start covering the main receptor types of the endocannabinoid system, here are a few interesting facts about the ECS in general:
- Besides humans, every other vertebrate species (animals with a spine) possess an endocannabinoid system.
- The most primitive animal that expresses an ECS is the sea-squirt (also called tunicate), which has evolved around 600 million years ago.
- In humans, the endocannabinoid system is fully operational before we leave our mother’s uterus. (1)
Receptors of the endocannabinoid system
These cellular receptors are responsible for our body’s reaction to endocannabinoids, but also the cannabinoids from pot.
There are main two distinct types of cannabinoid receptors, and they can be considered as “locks” that are present on the membranes of different types of cells in our body.
The endocannabinoid and cannabinoid compounds act as “keys” which trigger a specific response from these cell, upon entering the “lock” of the receptors.
CB1’s are the most abundant cannabinoid receptors in the body, and are mostly located in the central nervous system (CNS), more precisely the brain and the spinal cord.
In the brain, the largest quantity of the CB1 receptors is present in the:
- Frontal cortex (where thinking happens)
- Hippocampus (in charge of memory)
- Cerebellum (in charge of movement)
- Basal ganglia (associated with voluntary movement, learning, cognition and emotion)
Other than the central nervous system, CB1 receptors are found in the vital and reproductive organs, various glands, gastrointestinal and urinary tract, white blood cells and connective tissues.
CB2 is the second most prominent cannabinoid receptor, and unlike CB1, it is mostly found in the gastrointestinal (GI) tract, where the most of the body’s immune system is located.
Large concentrations of CB2 receptors are also found in the tonsils and the thymus gland, and both sections of the body are also valuable assets of the immune response.
CB2 receptors are (just like CB1) expressed in some neuron cells (like the microglia) in the brain and other parts of the central nervous system, but in much smaller quantities than CB1.
Another captivating attribute of the ECS is that both the cannabinoid receptors and the internal endocannabinoids get synthesized in the body on demand.
This basically means that when our body “senses” that additional receptor / endocannabinoid expression will return our organism into a state of homeostasis (balance), both the receptors and the compounds get synthesized on demand.
Studies have shown that this trait of the ECS occurs in situations like nerve injury, inflammation and tissue damage. (2)
Here are a few more facts about the ECS’ receptors:
- It is speculated that CB1 and CB2 receptors are more numerous than any other receptor system in the human body (including the receptors of neurotransmitters dopamine and serotonin)
- Numerous parts of our body contain both CB1 and CB2 receptors, and they are found on many intersections of our body (the borders of two or more different physiological systems), contributing to the communication and cooperation of differing types of cells
- Besides CB1 and CB2, certain (endo)cannabinoids activate other receptors in the body, including the TRP (transient receptor potential), and PPAR’s (peroxisome proliferator activated receptors)
Very similar to our current understanding of cannabis-derived cannabinoids, contemporary science has currently figured out the precise mechanisms of action of two internal endocannabinoids, anandamide and 2-AG.
Even though we don’t understand everything, the ongoing research has provided us with great insight about the functioning of the ECS, and the extremely diverse roles of these endogenous compounds.
Anandamide (N-arachidonoylethanolamine, or AEA)
Anandamide is the most thoroughly studied endocannabinoid, and was discovered in 1993 by Raphael Mechoulam. The name is derived from the sanskrit word “ananda”, meaning bliss or delight, which is one of the main cerebral effects of anandamide.
The role of this compound is profoundly diverse, helping to regulate numerous processes that include the immune system function, central nervous system function, appetite, pain, memory and much more.
Anandamide is an activator (agonist) of both CB1 and CB2 endocannabinoid receptors, meaning it is created (synthesized) throughout the tissues of our body, which also explains its divergent effect on our organism.
I already mentioned that both endocannabinoids and endocannabinoid receptors get synthesized on demand, meaning our body makes them once it “senses” the need for these compounds.
Exercise boosts anandamide levels
The best example of this phenomena is the “runner’s high”, where long-distance runners experience an intensely visceral euphoric feeling, and this sensation is actually anandamide’s doing.
Scientists have observed that prolonged aerobic exercise (over 30 minutes) increases anandamide levels (3), complimenting to that joyous feeling we experience after hard physical labour.
Marathon and triathlon competitors experience increased levels of anandamide in the greatest possible extent as their aerobic exercise is really intense and very durable at the same time.
Anandamide affects memory and forgetting
What’s also fascinating is the effect anandamide has on memory. Naturally you’d assume that it increases or enhances our memory, but the truth is this compound has a very important role in forgetting.
This might seem somewhat unusual at first but consider how much input we receive from our senses daily. For instance, the amount of faces we see every time we ride the subway.
For our brain to store things worth remembering, unneeded information has to be “deleted”.
Anandamide’s “forgetting” function is also very important for traumatic and extremely stressful events, and people suffering from PTSD have a very hard time disconnecting from the trauma they’ve experienced.
This is why CBD works wonders for anxiety (4) and also PTSD patients.
I previously mentioned that endocannabinoids are created and degraded by certain enzymes in our body.
Cannabidiol (CBD) lessens the production of a specific enzyme that is responsible for degrading (or “recycling”) anandamide.
By diminishing the amounts of the FAAH (fatty acid amide hydrolase) enzyme, anandamide is left to engage the receptors of the endocannabinoid system for extended periods of time, leading to a diminishment of general anxiety, but also the stress caused by PTSD.
Genetic mutations increase anandamide levels
The exact same mechanism of degrading anandamide with FAAH enzyme is also what separates entire happy from unhappy nations (5), which was noticed by examining their “levels of happiness”.
This research gave us an insight that specific genetic mutations are responsible for different levels of FAAH enzyme in the body, and lesser quantities of this enzyme directly correlates with a constantly better mood, and a general sense of wellbeing.
The science team behind this study also noted that a sense of happiness of course isn’t only dependent on this connection, but also depends on a complex mixture of economic and political factors.
Foods that increase anandamide production
Some foods are can boost anandamide levels, and some can slow down the metabolization of FAAH enzyme which degrades it.
Pure chocolate affects anandamide levels in two ways: It increases the number of available endocannabinoid receptors that can be triggered by anandamide, and second is that it diminishes the levels of FAAH enzyme which “destroys” it.
Unlike chocolate which influences the ECS in more subtle ways, black truffles have the anandamide compound in them, and when eaten they directly increase the levels of this endocannabinoid in our body.
What’s also fascinating about these mushrooms is that they don’t have any endocannabinoid receptors whatsoever, and it is theorized that the presence of anandamide acts as a tactic for spreading the spores (their asexual reproductive units), by attracting predators to eat them, and subsequently spreading their spores to nearby surfaces.
This compound is found in many fruits and vegetables like apples, grapes, onions, potatoes, tomatoes and broccoli. Besides being a powerful antioxidant and reducing oxidative stress, kaempferol also inhibits the synthetization of FAAH enzyme, thus prolonging the duration and effect of anandamide.
Omega 3 Fatty Acid
Consuming these polyunsaturated fatty acids found in fish oil, krill oil, hemp and flax seeds has shown to increase the vigilance of the endocannabinoid system (6).
This is the second most prominent endocannabinoid found in our body, but currently it isn’t nearly as researched as anandamide.
What we do know so far is that 2-AG is present in much larger quantities in the central nervous system (brain and spinal cord) than anandamide.
2-AG is also an agonist (triggers a biological response) of both CB1 and CB2 endocannabinoid receptors.
What’s also interesting is that 2-AG is a high efficacy agonist of endocannabinoid receptors, while anandamide is described as a low efficacy agonist for CB1, and a very low efficacy agonist of CB2 receptors (7).
What additionally separates anandamide and 2-AG is that the enzymes which synthesize and degrade these endocannabinoids are completely different – anandamide is degraded by FAAH, and 2-AG is degraded by an enzyme called MAGL (monoacylglycerol lipase).
This entails that they have completely different roles within the ECS, but both are tools for maintaining balance within an organism, which is the primary function of the endocannabinoid system.
Researchers will undoubtedly provide us with additional knowledge about this enigmatic compound soon.
Endocannabinoid system deficiency
Clinical Endocannabinoid Deficiency (8) (or CECD), is a health condition where the body doesn’t produce adequate quantities of endocannabinoids, or it doesn’t produce the needed amount of endocannabinoid receptors.
Another possible cause for CECD can also be that the body produces too many enzymes (FAAH, MAGL), that break down the endocannabinoids before they get the chance to affect the receptors.
As a result of this deficiency, a weakened ECS cannot properly maintain homeostasis (a balance of interconnected systems within an organism).
Clinical Endocannabinoid Deficiency was first described by Dr. Ethan Russo, who’s been on the forefront of modern cannabis research during the last two decades.
According to his research, clinical ECS deficiency can have a negative influence on many conditions and diseases, including:
- Irritable Bowel Syndrome (IBS)
- Post-traumatic Stress Disorder (PTSD)
- Multiple Sclerosis
- Parkinson’s Disease
- Chronic Pain
- Muscle Spasms
- Mood Imbalances and Irritability
All of this may seem a bit far-fetched to someone who isn’t acquainted with the incredibly diverse role the ECS plays in our body.
But if official scientific research concluded that a malfunctioning endocannabinoid system is connected to so many physiological issues, this directly coincides with why cannabis is a valid and successful treatment method for so many conditions, disorders and diseases, such as:
- Post-traumatic Stress Disorder (PTSD)
- Amyotrophic Lateral Sclerosis (ALS)
- Parkinson’s Disease (PD)
- Crohn’s Disease
Even though the number of scientific studies that deal with medical cannabis, endocannabinoid system and cannabinoids from cannabis is now counts over 24.000 different articles, many people are still very skeptical about the healing properties of this plant.
Considering the decades-long global illegality of cannabis, this doesn’t really come as a surprise.
Taking your health into your own hands is something I consider a personal responsibility, especially when the medicine in question is something completely natural and has existed on this planet long before humans.
Another reason that demands for self-education about cannabis and health is that very few doctors know anything about the ECS, and the effects of endocannabinoids and cannabinoids.
This survey from 2013 was conducted by the Medical Cannabis Evaluation. It questioned medical schools in the US if the endocannabinoid system is a part of their curriculum.
The survey found that only 13% of schools were teaching future doctors about the ECS.
I hope that this percentage increased since 2013, but I’m certain that the increment is miniscule.
This implies that the chances of your personal doctor knowing anything about the ECS (and how it can be positively influenced by cannabis) are very slim.
What’s also very important to understand is that by consuming cannabinoids from cannabis (which are health-beneficial by themselves), we also increase the quantity of both cannabinoid receptors, and our internal endocannabinoids.
Small and carefully thought-out doses “force” our body to produce more of its endogenous cannabinoids like anandamide and 2-AG, and at the same time increase the concentration of cannabinoid receptors CB1 and CB2 (9).
This is very valuable to people whose endocannabinoid system is not functioning properly, but more importantly it demonstrates that cannabinoids from cannabis aren’t just a simple cure—they are also a tool that helps our body increase the production of its own internal health regulators.
A greater number of receptors means that lesser quantities of cannabinoids are needed to produce a desired effect, and a carefully planned intake of cannabinoids also increases the amount of available endocannabinoids.
Check out our all-inclusive dosage guidebook to learn more about how to correctly and accurately dose cannabis. For the purpose of this guide we’ve collaborated with Dr. Dustin Sulak who is one of the top-tier cannabis physicians in the US and has extensive experience with treating patients with medical cannabis.
What’s also very important to mention when consuming cannabinoid-based derivatives for medicinal purposes, it is of utmost importance to consume products that aren’t isolated compounds, but instead have a full-spectrum of cannabinoids in them, just like the real plant.
Besides THC and CBD, each strain of cannabis has a vast number of accompanying compounds that (even if they are found only in trace amounts) add to the synergistic effect of cannabis as a whole, in what’s dubbed the entourage effect.
Synthetic cannabinoids or isolated THC/CBD medications don’t have any minor cannabinoids or terpenes in them, and because of this they lack the cooperative effect leading to a much weaker therapeutic impact.
To conclude, the state of our endocannabinoid system is very important as its purpose is to help regulate the proper functioning of all other physiological system of our body.
The cellular receptors of the ECS can be positively influenced by cannabinoids from cannabis, causing incredibly diverse effects which are completely dependent on the medical issue in question, but the end goal is always the same:
Homeostasis, a state of equilibrium of an entire organism.
Cannabis is such a powerful medicine for an incredibly large number of conditions because it directly influences an ancient and all-encompassing system in our body.
Further educating yourself on this complex and fascinating topic can bring you nothing but good.
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- Shenglong Zou and Ujendra Kumar; Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System; 2018
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