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Understanding your Endocannabinoid System – How Active Cannabinoids Interact with your Endocannabinoid System

The study of the endocannabinoid system (also referred to as ECS or endogenous cannabinoid system), has been gaining momentum ever since the first cannabinoid receptor was discovered in the 1980s. In a nutshell, the endocannabinoid system consists of cannabinoid receptors sharing a collective function: to regulate human health and promote homeostasis throughout the human body.

But why understanding your endocannabinoid system even matters

Understanding your ECS is a crucial part of attaining an in-depth comprehension of the incredible ways marijuana consumption affects your mental and physical state. By apprehending how active cannabinoids interact with your endocannabinoid system, you can learn how to reap the full array of benefits of the green medication, no matter if it comes to recreational or medical marijuana use.

We invite you to join us on a journey that will forever change your relationship with cannabis in a beautiful, meaningful, and profound manner.

ECS (Endogenous Cannabinoid System): Discovery, Functions, & More!

Before scientists were able to identify and introduce the endogenous cannabinoid system to the public, it was solely through animal studies that the experts were granted the opportunity to first discover the existence of cannabinoid receptors that make up the ECS.

It was in the mid-1980s at Allyn Howlett’s laboratory (St. Louis University)that the first cannabinoid receptor was discovered, thanks to the finding that cannabinoids possess the ability to inhibit adenylate cyclase acting through Gi/o proteins.

Later on, in 1988, Allyn Howlett’s laboratory collaborated with Bill Devane, making a second groundbreaking finding. The team of researchers found out that there are, indeed, specific receptors which interact exclusively with receptors present in tetrahydrocannabinol (THC).

Most importantly, the team of researchers discovered that these unique receptors are found in high concentration in particular parts of the brain. The parts of the brain where these receptors were highly concentrated are responsible for an array of crucial physiological and mental processes, such as high cognition, memory, motor coordination, and emotions.

While 1988 marked the discovery of only a single group of cannabinoid receptors, just five years later, in 1993, scientists identified the existence of the second group of cannabinoid receptors. These cannabinoid receptors were not concentrated in the brain, though. Instead, they were found to be distributed throughout the peripheral tissues of the body, as well as the immune system.

When it comes to the reaction to THC exhibited by the first and the second group of cannabinoid receptors, researchers concluded that it is pretty much the same.

Regardless of the indisputable significance of the groundbreaking findings of cannabinoid receptors in the 1980s, it wasn’t before 1995 when researchers could finally conclude that these amazing receptors (nowadays known as CB1 and CB2 receptors), were not found only in rats but in thousands of species, including but not limited to humans.

Ever since the 1995s, the science behind cannabis, active cannabinoids and the endogenous cannabinoid system has gone a very, very long way.

Nowadays, if you Google the scientific journal articles that contain the word “cannabis,” search engines will reveal more than 10 000 results. In fact, if you search for the word “cannabinoid,” the results will rapidly increase, letting you browse through way over 20 000 articles on an average.

If we calculate the speed of scientific publications related to cannabis and cannabinoids, we can quickly sum up that over the last 20 years, at least two scientific publications on the topic have been steadily released every single day.

What these numbers illustrate is that the science behind cannabis has finally managed to grab the attention of professional researchers and cannabis consumers alike, and this is for some solid reasons.

Understanding the endocannabinoid system is bound to write new pages in the history of mankind.

We have reached a stage in our collective development as human species when we can fully investigate, realize, and apply the attained knowledge regarding cannabis use and the ways cannabinoids interact with our endogenous cannabinoid system to help us maintain a healthy, happy life on both mental and physical level.

The major function of your endocannabinoid system is the maintenance of a “relatively stable equilibrium” through physiological processes accomplished between otherwise independent elements in your body; a process known as homeostasis.

https://www.youtube.com/watchv=Iz0Q9nTZCw4

Video by: Amoeba Sisters – Homeostasis and Negative/Positive Feedback
Source: youtube.com

But apart from promoting homeostasis, the way different cannabinoids interact with the endocannabinoid system can help to target and address particular issues and/or disorders, related to pain, inflammation, stress, memory, as well as the immune, cardiovascular, and muscular system.

The Invaluable Role of Cannabinoids

Quintessentially, cannabinoids are compounds that interact with the body’s endocannabinoid system. The endocannabinoid system consists of a whole network of receptors that interact specifically with cannabinoids, thus, maintaining vital functions throughout the body.

Indeed, cannabinoids do promote homeostasis. Most noteworthy, cannabinoids promote homeostasis at every level of biological life, as deep as the subcellular level.
To illustrate the magnificent action of cannabinoids, let’s look into a process known as autophagy.
Autogaphyrefers to the process when a cell isolates a part of its content n order for that part to be recycled and self-digested. The process of autophagy is arbitrated by the cannabinoid system.

Autophagy is an extremely important process as it has a deadly effect on hostile tumor cells. However, simultaneously, autophagy allows normal cells to function properly by helping them maintain the much-needed balance between synthesis and recycling of cellular products.


Autophagy literally causes tumor cells to consume themselves; a process that can be pictured as a cellular suicide.

Taking this spectacular example in mind, one can understand the profound effects of cannabinoids that start at a cellular level but thanks to the promoted homeostasis, their beneficial action extends at the level of the entire organism.

Both endocannabinoids and cannabinoids can be found at the crossing point of various crucial systems in the body; systems that are in charge of coordination and communication between the different types of cells.
Let’s take, for instance, the site of an injury.

In the case of an injury, cannabinoids can decrease the release of both sensitizers and activators from the tissue that has been injured. Thus, cannabinoids stabilize the nerve cells in order to prevent excessive firing.

Moreover, as cannabinoids stabilize the nerve cells, the nearby immune cells are also calmed down, resulting in the prevention of pro-inflammatory substances being released by the nearby immune cells.
With this particular example, we can clearly see how complex is the interaction between the endocannabinoid system and active cannabinoids, involving not a single one but three different cells types and three different mechanisms for the sole purpose of alleviating the pain caused by injury, as well as minimizing the associated damage.

You can picture the endocannabinoid system like a bridge that interconnects the body and the mind.

The ECS maintains complex actions related to all of the organs found in the body, the immune system, and, nonetheless, the nervous system.
In fact, experts believe that understanding the endocannabinoid system and the way cannabinoids interact with this system is the beginning of a whole new era in attaining an in-depth, holistic health approach.

The ECS is a wonderful example of a mechanism that can explain that neither health nor disease is merely triggered and/or maintained on a physiological level. Instead, health or disease are promoted by states of consciousness, or in other words, promoted on a mental level, too.

Moreover, the invaluable role of cannabinoids extends beyond the cellular and the organism level. As it turns out, cannabinoids also influence our relationship with the surrounding environment.

By interacting with your endocannabinoid system, active cannabinoids do alter your behavior, and that’s not in the often aggressive way consumers tend to experience the after-effects of alcohol consumption.

In fact, according to an explicit study comparing the aggressive behavior during cannabis and alcohol exposure, cannabis intoxication was proven to decrease subjective aggression.

Cannabinoids administration is related to boosting creativity, the sense of collective belonging and sharing, as well as humor and sociability. Even in the cases when cannabinoids’ administration leads to states of introspection, this type of introspection can be extremely beneficial in coping with stress and depression, among other possible mental issues.

Last but not least, we need to take into consideration the fact that nowadays, we live in a fast-paced, quickly changing environment. Because of this, the ability of cannabinoids to mediate neurogenesis and their intriguing role in neuronal plasticity can significantly help us in moving away from outdated, old patterns and/or beliefs that negatively impact our personal development as human beings on the fragile journey we call life.

https://www.youtube.com/watchv=LNHBMFCzznE

Video by: TEDx Talks – After watching this, your brain will not be the same | Lara Boyd | TEDxVancouver
Source: youtube.com

In other words, cannabinoids do influence our ability to keep an open mind, ready to move away from limiting patterns, regardless of whether these limiting patterns are due to social conditioning, trauma from past situations or merely our state of mind.

Cannabinoid Receptors and Active Cannabinoids

The way active cannabinoids interact with the cannabinoid receptors of your endocannabinoid system is simply whimsical.

According to scientists, the endocannabinoid system has evolved back to as far as 600 million years ago in primitive animals. In fact, it is thanks to the function of the endocannabinoid system how various primitive animal species such as all vertebrate, tiny nematodes, and sea squirts, among others, managed to adapt to the changes in the environment.

The science behind the intricate ways active cannabinoids work on cannabinoid receptors is currently under rapid development. As of 2019, the most studied (although not entirely studied!) cannabinoids are THC and CBD. Fortunately, research (yet not sufficient enough) has been done on other cannabinoids, such as CBC, CBN, and CBG.

But the truth is, there are over 113 active cannabinoids present in cannabis plants that have been isolated by scientists up-to-date! With this in mind, it is more than crystal clear that we are still at the very brink of gaining a much more in-depth understanding of the unique role of the different cannabinoids on the endocannabinoid system.

Most importantly, there are many large gaps to be filled regarding active cannabinoids. These gaps include but are not limited to understanding the complex interactions between the different cannabinoids (the complexity of the interaction between various cannabinoids’ has been introduced with the term “entourage effect,” also referred to as “ensemble effect”).

Also, scientists need to find out more about the interaction between various cannabinoids, different cell types and different systems in the body.

Not the least, external factors such as your current mental, physical, and emotional state do further lead to different interactions between your body and active cannabinoids.

However, the puzzle regarding active cannabinoids and their action on cannabinoid receptors is actually not a paradoxical riddle but a beautiful challenge that allows scientists to think about health and physiology in new, never-seen-before ways; as if making the tiny pieces of a puzzle fit into “the big picture.”

But what have we learned about cannabinoid receptors so far

Cannabinoid receptors are literally embedded in cell membranes. These receptors are present throughout the human body. Experts believe that cannabinoid receptors are actually the most numerous types of receptors, as opposed to the receptors in just about any other receptor system.
The stimulation of cannabinoid receptors leads to a wide variety of physiologic processes to start taking place.
Up to the present day, researchers have been able to identify two cannabinoid receptors.

CB1
receptors are predominantly found in the nervous system, glands, organs, connective tissues, and gonads.

CB2 receptors
are predominantly found in the immune system and the immune system-associated structures. While many tissues do contain both CB1 and CB2 receptors, each is linked to a different action.

While still only an assumption, some researchers believe that there might be a third cannabinoid receptor system that is still waiting to be discovered.

Endogenous Cannabinoids (Endocannabinoids) VS Phytocannabinoids VS Synthetic Cannabinoids

Apart from being able to interact with the active cannabinoids present in cannabis, the human body does produce and interact with its natural cannabinoids, too. This type of cannabinoids is known as endogenous cannabinoids.

Quintessentially, endogenous cannabinoids are neurotransmitters that are being produced within your body. Endogenous cannabinoids bind to cannabinoid receptors located in the brain and immune system, much like active cannabinoids found in cannabis do.

Some of the endogenous cannabinoids (also known as endocannabinoids) produced within your body include virodhamine (OAE), anandamide, 2-arachidonoylglycerol (2-AG), and n-arachidonoyl dopamine (NADA).

Interestingly, endocannabinoids perform much differently than other well-known neurotransmitters such as serotonin, dopamine, and norepinephrine.

Let’s look at the way dopamine performs.

For a start, dopamine needs to be synthesized in advance. Next, it is stored in the vesicle. Subsequently, dopamine requires to be stimulated. In response to stimuli, dopamine is then released from the presynaptic cell. After crossing synapse, dopamine lands on the postsynaptic cell, thus, causing activation.

However, endocannabinoids are not synthesized in advance. Being key components of cellular membranes, your body produces endocannabinoids “on demand.” Also, endocannabinoids are hydrophobic, meaning that they cannot travel far in the body as other neurotransmitters can. Instead, the effects of endocannabinoids are localized.
What’s more, endogenous cannabinoids move or travel in the exact opposite direction to other neurotransmitters. Thus, endocannabinoids need to first leave the postsynaptic cell in order to end at the presynaptic cell. The presynaptic cell has high concentrations of axons. It is axons that are responsible for the release of “traditional” neurotransmitters such as dopamine and anandamide, among others.

In a nutshell, endocannabinoids are synthesized on-demand, they have a local effect and a pretty short life as they are quickly degraded by the enzymes monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH). Endocannabinoids are naturally produced within your body.

On the other hand, the active cannabinoids found in cannabis plants are phytocannabinoids.

Phytocannabinoids
are plant substances. These plant substances are similar to endocannabinoids as both stimulate cannabinoid receptors.

For example, THC, CBD, and CBN, to name a few, do all belong to the category of phytocannabinoids.

Up-to-date, most phytocannabinoids have been isolated from cannabis sativa. However, it is good to keep in mind that there are other medicinal herbs, such as, echinacea purpura, that has been discovered to contain non-psychoactive cannabinoids.

But phytocannabinoids do not merely serve the purpose of binding with cannabinoids receptors in your endogenous cannabinoid system.

Amazingly, cannabis plants also use THC, as well as other phytocannabinoids, for the purpose of promoting plant health and the prevention of disease.
To illustrate this better, cannabinoids are proven to possess antioxidant properties. Thanks to these properties, cannabinoids can protect the leaves and flowers/buds from ultraviolet radiation. This is possible as cannabinoids are able to neutralize the harmful UV rays-generated free radicals, thus, protecting the cells of the plant from damage.

It is no secret that antioxidants found in various plants have long been promoted for their ability to prevent free radical harm, being an all-natural option to synthetic antioxidants.We must not forget that free radicals cause impaired healing, cancer, and aging in humans, therefore, antioxidants are truly invaluable to our well-being.

But are the plants the only living creatures capable of producing cannabinoids, apart from the fact that our bodies do produce certain endocannabinoids, too

Nowadays, laboratories are also able to produce cannabinoids. For instance, the FDA has approved nabilone (Cesamet) and dronabinol (Marinol), both of these drugs containing synthetic THC and available to patients who need to treat wasting syndrome and severe nausea. Nevertheless, some clinical experts have found these FDA approved synthetic cannabinoids-based drugs being helpful for the treatment of migraine and chronic pain, too.

When it comes to animal research, it is also synthetic cannabinoids that are being used by researchers. Keeping in mind that this type of cannabinoids is synthetically produced, some can reach 600 times the maximum potency of THC.

The Takeaway

Above all, phytocannabinoids, endocannabinoids,and synthetic cannabinoids share one single thing in common: these active cannabinoids do act upon your cannabinoid receptors.

However, the action of these types of cannabinoids on your endocannabinoid system does differ a lot.

While we are excited to trace the spectacular advance in the science behind different active cannabinoids, their complex interactions, and the different effects produced on a physical and mental level, we need to note that there is no other plant on planet Earth that is known to produce so many different phytocannabinoids as cannabis.

Most importantly, even though the “entourage effect” remains only a theory up-to-date because much more research is needed on that matter, there is no doubt that the different phytocannabinoids work in synergy, increasing the potential and efficacy of cannabis treatment. The living nature is the greatest scientist, the greatest teacher, and the greatest healer. Or as some experts dare to claim, it seems that our bodies were simply designed to work with the active cannabinoids present in cannabis plants to maintain homeostasis in the most natural way possible.

How THC Interacts with your Cannabinoid Receptors

It is well-known that THC is in charge of triggering the sense of high, or in other words, the intoxicating effects of cannabis consumption. While experiencing the high is not what all marijuana users enjoy, THC has the ability to stimulate and enhance the beneficial, healing effects of other active cannabinoids.
THC and CBD have different molecular structures. With this in mind, THC and CBD do not interact with the CB1 and CB2 receptors in the exact same manner.
Thanks to its molecular structure, THC binds directly with CB1 receptors. Once the bond between THC and CB1 receptors is formed, the brain receives signals resulting in the psychoactive effect of “getting high.”

As discussed above, CB1 receptors are located predominantly in the brain and nervous system but they can be also found in the kidneys, lungs, and liver.

Both natural endocannabinoids, as well as the cannabinoid THC, do majorly bind with CB1 receptors. As a result of THC’s interaction with the cannabinoid receptors that make up the endocannabinoid system, patients can experience efficient relief from nausea, pain, depression, and inflammatory-related issues, among others.

How THCA Interacts with your Cannabinoid Receptors

Surprisingly (or not at all), the most common active cannabinoids found in cannabis, namely THC and CBD, are not the exact compounds present in cannabis plants in raw form.

Instead, THC and CBD are created once THCA (tetrahydrocannabinolic acid) and CBDA (cannabidiolic acid) are converted to THC and CBD after being exposed to heat or ultraviolet light.

To be even more specific, the “mother” of THC, CBD, CBG, and CBC is actually CBGA (cannabigerolic acid). In a nutshell, the function of the CBGA cannabinoid for cannabis plants and the formation of THCA, CBDA, and CBCA is best to be compared to the function of stem cells for the human body.

Most noteworthy, even before getting converted into THC, CBD, etc., the acidic forms of the active cannabinoids do still provide profound effects on cannabinoid receptors, except for, there is no way to experience the sense of high as all cannabinoid acids are non-intoxicating. With this in mind, there are actually plenty of solid reasons why juicing raw cannabis has been gaining momentum. In its raw form, the non-psychoactive THCA, along with other cannabinoid acids, may have a whole multitude of therapeutic applications.
Many experts refer to raw cannabis juicing as one of the most effective ways to take utmost advantage of active cannabinoids while also maximizing the benefits of cannabis-based treatment.
Indeed, in their acidic forms, cannabinoids can be consumed at much higher levels as opposed to consuming cannabis once THCA has been converted to THC.

Moreover, THCA has shown very promising potential in acting as an effective antioxidant, neuroprotectant, antispasmodic, appetite stimulant, anti-inflammatory, anti-emetic, pain relief, and an anti-proliferative agent.

Apart from juicing raw cannabis, THCA can be administrated through various topicals, capsules, and tinctures.
Since THCA is the molecular precursor of THC, it is not known to bind closely with either the CB1 or the CB2 receptors.

However, THCA is believed to interact with another group of receptors – the 5-hydroxytryptamine (5-HT) receptors – acting like a possible agonist that plays a key role in serotonin output.
Furthermore, THCA in conjunction with other acidic cannabinoids is believed to act as an inhibitor to enzymes known as COX-1 and COX-2. Therefore, THCA along with other acidic cannabinoids has shown promising results for coping with both pain and inflammation. On top of that, THCA has shown high potential in boosting levels of the endocannabinoid 2-AG. 2-AG is a well-known modulator of numerous health functions.

How CBD Interacts with your Cannabinoid Receptors

CBD ingestion can be extremely efficient in the reduction of a wide range of symptoms related to various diseases and disorders, such as depression, anxiety, opioid withdrawal, chronic inflammation, epilepsy, multiple sclerosis, diabetes, and rheumatoid arthritis.

CBD’s action on cannabinoid receptors is very complex as CBD acts upon both CB1 and CBD2 receptors. Moreover, CBD does not bind directly to CB1 or CB2 receptors. The way CBD interacts with your cannabinoid receptors is actually indirectly.

The indirect impact of CBD on cannabinoid receptors is possible as CBD activates TRPV1 receptors.
TRPV1 receptors are in charge of vital functions including body temperature regulation, pain perception, and, nonetheless, inflammation. Furthermore, CBD is capable of increasing the levels of anandamide (the neural generator of motivation and pleasure) in the body.

How CBC Interacts with your Cannabinoid Receptors

Cannabichromene (CBC) is an active cannabinoid that does not lead to intoxicating effects. Most importantly, CBC is believed to possess very high therapeutic potential.
Even though more research is needed, CBC is thought to have pain relieving and anti-inflammatory properties. Cannabichromene is also promising in terms of its antifungal and antibacterial properties. CBC may also assist with gastrointestinal/ digestive disorders.

What has put CBC in the spotlights of researchers and scientists is that it might be very valuable for addressing neurodegenerative related disorders. CBC believed to most probably contribute to brain cells’ regeneration, thus, being a highly sought after the agent for the treatment of fibromyalgia, Alzheimer’s, multiple sclerosis, and dementia.
Naturally, most cannabis strains contain low levels of CBC. Despite the low levels of CBC, experts believe that CBC does play a key role in maximizing the effectiveness of the medicinal spectrum of the whole plant when paired with terpenes and different other cannabinoids.

Most experts consider that CBC binds indirectly with the endogenous cannabinoid system’s receptors. While CBC does not bind directly with CB1 or CB2 receptors, it does seem to stimulate some of the body’s endocannabinoids, namely 2-AG and anandamide.

Also, CBC may work as an agonist to the TRPV1 and TRPA1 receptors.

TRPV1 and TRPA1 receptors are closely related to the modulation of neurogenic inflammation, body temperature, and pain sensitivity. To be as concise and precise as possible, CBC is believed to possibly bind with CB1 and CB2 receptors but only minimally, although more research is needed on that matter.

How CBG Interacts with your Cannabinoid Receptors

CBG (Cannabigerol) is similar to CBD and CBC as it has no intoxication-inducing properties. Much like CBC, CBG is naturally present in very low levels in most cannabis varieties. However, nowadays there are particular hemp varieties that are intentionally cultivated for the purpose of providing high CBG yield.

On top of that, CBG does play a very special and important role in the biochemistry of cannabis plants.

It is 6-8 weeks into the flowering cycle of cannabis plants when CBG starts acting as a chemical precursor to THC and CBD cannabinoids.

CBG does interact with both the CB1 and CB2 receptors. The particular role of CBG is associated with inhibiting the intoxicating effects of THC.

Nonetheless, CBG is believed to boost anandamide. Anandamide, being a vital endocannabinoid, is related to the regulation of appetite, mood,and sleep, as well as the boost of dopamine levels.
As it is believed to block the uptake of GABA in the brain, experts attribute muscle-relaxing and anti-anxiety properties to CBG. But CBG may even be able to obstruct serotonin receptors, therefore, it is considered to potentially possess antidepressant properties.

Other potential health benefits of CBG’s action on your endocannabinoid system may include antioxidant, antibacterial, antitumor, anti-inflammatory, antifungal, and neuroprotective properties, among others.

How CBN Interacts with your Cannabinoid Receptors

Interestingly, it was CBN and not THC that was the first cannabinoid to be successfully isolated. Thus, experts used to believe it is CBG causing the psychoactive effects of cannabis consumption before THC was discovered later on.
Because of its sedative properties, Cannabinol (CBN) is described as a mildly psychoactive cannabinoid.

It can be summed up that Cannabinol is present in high abundance in cannabis plants, although this depends on whether or not THC has been oxidized to the point of degradation. Simply put, CBN is a byproduct of THC. When oxidized THC degradation takes place, THC actually converts to CBN. Albeit, most cannabis strains do not naturally produce high levels of CBN in the absence of THC degradation.

More importantly, marijuana growers can easily manipulate the levels of CBN present in their harvest.

In fact, if you have ever happened to come across some long-forgotten cannabis leftovers in your green medication jar, you might have noticed that the flavor and smell are missing (terpenes have degraded) and that the uplifting effects associated with consuming this particular strain have been prevailed by detectable sedation after consumption.

It’s good to keep in mind that CBN shares a similar chemical composition to THC.
Experts state that CBN is known to bind primarily with the CB2 receptors. However, CBN is also believed to interact with the CB1 receptors.

What makes CBN potentially effective for alleviating pain and inflammation, regulating bone health, lowering blood pressure, convulsions, and treating various skin conditions is CBN’s agonist action to the TRPV2 receptor. Naturally, the TRPV2 receptor produces a protein that is in charge of regulating several biological systems in the body.

Last but not least, high levels of CBN can provide effective anti-anxiety and insomnia-battling properties. As far as inducing sleep is concerned, CBN is considered to be most effective in combination with other cannabinoids, e.g. CBD and THC.

Understanding your Endogenous Cannabinoid System: Final Thoughts

The endogenous cannabinoid system (also known as endocannabinoids system or ECS), phytocannabinoids, endocannabinoids, cannabinoid receptors – the science behind the way cannabis consumption influences our bodies on both mental and physical level is anything but boring.

Full of paradoxes, riddles-yet-unsolved but also full of bright hopes and potential health benefits that extend way beyond anything that mankind knew so far, the world of cannabis is changing the history of humanity.

Respect the green medication, know what you are consuming, join the unique revolution of spreading the innovative knowledge about human health, well-being, and cannabis. One day, the endocannabinoid system is bound to be studied by students in a biology class just like all the rest of the important systems that make up who we are not merely on a physical but on a mental and emotional level, too.
For understanding your endogenous cannabinoid system, as well as how active cannabinoids interact with your endocannabinoid system, picture the way your feet fit into a pair of shoes. For over a century, it’s as if we’ve been walking barefoot in the world of holistic health, well-being and effective, affordable, natural medication, as our “shoes” (think of active cannabinoids) have been missing out from the big picture due to numerous regulations and restrictions.

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