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The Endocannabinoid system: a universe inside us
By Anastasia Myronenko

Anastasiia Myronenko

Anastasiia Myronenko is a Medical Physicist actively practicing in one of the leading cancer centers in Kyiv, Ukraine. She received her master’s degree in Medical Physics at Karazin Kharkiv National University and completed Biological Physics internship at GSI Helmholtz Centre for Heavy Ion Research, Germany. Anastasiia Myronenko specializes in radiation therapy and is a fellow of Ukrainian Association of Medical Physicists.

The Endocannabinoid system: a universe inside us

alphagreen endocannabinoid system

In school, we all have been taught that there are 11 major organ systems in our body. Namely, these are: circulatory, respiratory, urinary, reproductive, integumentary, skeletal, muscular, nervous, endocrine, lymphatic, and digestive.

All of the systems listed above make up the human body and are the essential aspects of our health and wellbeing. Nevertheless, the list of the systems is not complete; indeed, it includes one more: the endocannabinoid system. Most of us probably have never heard of this system, with the exception of those who work with medicinal cannabis or are research scientists.

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As for the rest of us – it is not common to know what the ECS is and why it is so important. As a result, we are going to shed light on this theme and deepen your knowledge about cannabinoids and their influence in our bodies.

The endocannabinoid system, or ECS, was first identified around twenty-five years ago. It has been called the most important physiological system involved in stablising and maintaining human health. The discovery of the endocannabinoid system is considered one of the most significant medical breakthroughs in recent years. Before we delve into the history of the ECS, let’s firstly take a look at three primary components of the endocannabinoid system:

  • Endogenous cannabinoids. “Endogenous” means our body makes these compounds. Endocannabinoids are responsible for the activation of the endocannabinoid system. Well known to many of us, the neurotransmitters serotonin and dopamine are the nervous system’s chemical “messengers”. Similarly to these neurochemicals, endocannabinoids are the “messengers” working for the endocannabinoid system. Endocannabinoids are produced throughout the body. Two key endocannabinoids circulating through the body include:
    • Anandamide;
    • 2-arachidonoylglycerol. 

Similarly to the phytocannabinoids in cannabis, these compounds are built from lipids. Speaking of lipids, it is the lipid-based structure of cannabinoids that is the primary reason why the typical cannabis extract comes in the form of an oil, using a carrier oil as a base, such as coconut oil.

  • “Bad” enzymes. FAAH and MAGL enzymes represent the second component of the endocannabinoid system. These compounds break down the endocannabinoids, resulting in disruptions in the ECS’s work. 
  • The cannabinoid receptors. To continue the analogy that endocannabinoids are like the ECS’s “messengers”; this means cannabinoid receptors are the guards waiting for the messengers on the city wall. Receptors located on cell surfaces wait for the specific neurotransmitter to bind to them. Depending on the type of cell on which the receptor is situated, the final effect will rapidly impact mood, sensation, immunity and even consciousness. There are two types of cannabinoid receptors:
    • CB1 receptors;
    • CB2 receptors.

We will take a more in-depth look at these receptors later; for now we can just mention that CB1 receptors work mostly with our brain, central nervous system, and organs. CB2 receptors, on the other hand, can be found in the peripheral nervous system and immune system. 

To go back to the history of the endocannabinoid system, let’s look now to the year 1964: Raphael Mechoulam, a scientist from Israel, was conducting research on the cannabis plant. His findings changed the course of history for medical cannabis forever, as he was able to do something that nobody had ever done before: he isolated two compounds from the cannabis plant, signalling a new chapter in modern medicine. These two compounds were Cannabidiol and Tetrahydrocannabinol, known today by their abbreviations, CBD and THC, respectively. The discovery of these chemicals paved the way for the discovery of the endocannabinoid system in the decades that followed. 

After the “anabiosis” period, which lasted until late 1980, research of these exciting and promising areas became pretty robust, and the first cannabinoid receptor was found in the brain. The receptor was called CB1 and was mainly found on the sensory nerve fibres of the brain, the central nervous system, organs and glands. After that, in 1993, the second cannabinoid receptor called CB2 was found in the peripheral nervous system and the immune system. Does this mean that we were born with receptors sensitive only to chemicals found in a particular plant? It’s hard to believe, but yes! In 1992, Raphael Mechoulam, together with his research group, discovered the first endocannabinoid. The group decided to call it Anandamide, which in ancient Sanskrit means ‘bliss.’ It was found that Anandamide affects the CB1 receptor. Later, in 1995, Dr Mechoulam and his group of researchers discovered the second endocannabinoid, which was called 2-AG (or 2-arachidonoylglycerol). The main difference between the latter compound and Anandamide was that 2-AG had an affinity with both CB1 and CB2 receptors.

Research of the endocannabinoid system is still ongoing. Today, in the current period of the medicinal cannabis boom, it is essential to understand how it interacts with our bodies on a cellular level. It will allow you to garner the maximum effectiveness of CBD and help to avoid possible unexpected side effects from cannabis-infused medications. 

The mechanism of the ECS: All we need is … homeostasis?

alphagreen endocannabinoid system

To understand the whole picture of how the endocannabinoid system works, let’s take a closer look at each of the key players in this game. We have already mentioned above that there are three main components of the ECS:

  • Endocannabinoids;
  • cannabinoid receptors;
  • enzymes.

Endocannabinoids are produced throughout our body. Two key endocannabinoids are Anandamide and 2-arachidonoylglycerol. We now know that Anandamide was discovered as recently as 1992 by Raphael Mechoulam and his research group. The Anandamide molecule operates throughout our endocannabinoid system. It is involved in the regulation of such processes as memory, appetite, and pregnancy. Anandamide has also been identified as the source of the “runner’s high”, or the feeling of pleasure that we experience during or after intense exercise.

The second endocannabinoid 2-Arachidonoylglycerol or 2-AG doesn’t have such a glamorous name as its famous partner Anandamide, yet this does not mean it is any less critical. It was found that 2-AG has a direct impact on our emotional state. It is also responsible for maintaining cardiovascular health and protection from seizures.

Cannabinoid receptors are divided into two broad groups – CB1 and CB2 receptors. These receptors are located on the surfaces of the cells, and, depending on cell types, are sensitive to different types of endocannabinoids. We have the cannabinoid receptors throughout our bodies, and all of them are responsible for a wide variety of cell types and responses. 

The first group of cannabinoid receptors is called CB1 receptors. Receptors of this type are essential for the healthy functioning of our brain and are one of the most common receptors in our entire nervous system. CB1 receptors are distributed in different parts of the brain and depending on what region they are located, can moderate our mood, motor function, memory, and pain perception. Let’s check the “map” of the CB1 receptors’ distribution and their functions.

  • Cerebral cortex. Functions: decision making, cognition, emotional behaviour.
  • Caudate nucleus. Functions: learning and memory systems.
  • Putamen. Functions: regulation of movements, various types of learning.
  • Globus pallidus. Functions: control of voluntary movements.
  • Amygdala. Functions: responsible for stress and anxiety, emotions, pain and fear.
  • Hypothalamus. Functions: body temperature, feeding, neuroendocrine function.
  • Hippocampus. Functions: memory and learning.
  • Substantia nigra. Functions: regulation of addiction and movement.
  • Cerebellum. Functions: motor control and coordination.
  • Dorsal vagal complex. Functions: emesis. 
alphagreen endocannabinoid system

This type of cannabinoid receptor is also responsible for the psychoactive properties of cannabis when THC binds to them. 

CB1 types of cannabinoid receptors are most common in the central nervous system, although these receptors can also be found throughout the body but in significantly lower densities. CB1 receptors located in other parts of the body also play a vital role in pregnancy, digestion, cardiovascular health, and hormone production. 

The second group of cannabinoid receptors is called CB2 receptors. Receptors of this type are most often found on the cells of our immune system. CB2 receptors help to moderate inflammation and the response of our immune system to pathogens. Cannabis products aimed at combating conditions of an overactive immune system (such as arthritis, asthma, digestive issues (for example, inflammatory bowel disease), allergies, and autoimmune disorders), work directly with CB2 types of receptors. 

Besides the two types of cannabinoid receptors that Mother Nature has endowed us with, we also have two types of enzymes that break down the Anandamide and 2-AG. This process means our endocannabinoid system does not work as well as it should. These enzymes thereby play a negative role in our internal homeostasis. The two enzymes are called FAAH (Fatty Acid Amide Hydrolase) and MAGL (Monoacylglycerol Lipase), and it could be said that they really work against us. In fact, they impede our bodies from maintaining homeostasis and block its ability to reduce pain and inflammation. These two enzymes are usually produced in our body, but are over-produced when we are not as healthy as we should be. For example, in some instances of medication use; poor eating habits; lack of exercising; poor sleeping patterns and being overweight, our body feels additional stress and allows for a greater number of these enzymes to be produced. The enzymes “eat” away at our endocannabinoids – and when the ECS fails, our health fails too. The failure of our ECS can result in conditions such as depression, anxiety, pain, inflammation, digestive issues and more.

Enzymes in our endocannabinoid system are responsible for controlling when and where endocannabinoids are produced, and how quickly they get sequestered or broken down. These molecules work as an administrative system. FAAH and MAGL enzymes are always making sure the endocannabinoids are sent when and only when they are desired. Endocannabinoids in our body are synthesised from fats, and our body has a number of different enzymes working together to transform these fatty substances into Anandamide and 2-AG. When the body gets the signal to produce endocannabinoids, enzymes are put to work. It is also worth mentioning that by increasing the dietary intake of omega-3s and other essential fatty acids, this may boost the body’s production of endocannabinoids, as fatty acids work as specific “building blocks” for them.

Our endocannabinoid system is one of the central homeostatic systems in our body. It could be said that the ECS does everything possible to keep our internal balance and make us function at a more optimal level. When we feel anxiety, the ECS works to calm us down. When we feel sad or suffer from chronic depression, the endocannabinoid system works to lift us up. All the actions of this mechanism of neurotransmitters and receptors inside us are aimed at keeping our bodies functioning as optimally as possible. 

The process of reaching internal balance, step by step, goes like this:

  • First of all, nutritional and dietary factors are required as vital building blocks for the ECS to function normally.
  • An optimally functioning endocannabinoid system creates endocannabinoids based on the demands and needs of the body.
  • When created, endocannabinoids engage ECS receptor-sites in a lock-in-key fashion.
  • When engaged, neurotransmitters may be released, sending messages to cells, tissues, organs, and other systems in our body that are critical for our health.
  • Our body may maintain a constant balance of the endocannabinoid system by enzymatically degrading endocannabinoids when necessary. 
  • A perfectly functioning endocannabinoid system ensures harmony and balance in cells, tissues and organs, providing us with a state of equilibrium known as homeostasis.  
alphagreen endocannabinoid system

Cannabinoids and the ECS: Well-coordinated work is the key to success

After several decades of research on marijuana’s effects, scientists made several important discoveries. Besides identifying the active marijuana ingredient, they also discovered where and how it works inside us. Today, the endocannabinoid system and the active component of the cannabis plant – delta-9-tetrahydrocannabinol (THC) represent a unique communication system in our brain and body. Results of such an interaction affect many vital functions; including our feelings, moves and reactions.

We established earlier that the natural chemicals produced by our body interact within the endocannabinoid system and bind with receptors to regulate the essential body functions and processes. So, what are the roles of cannabinoids like THC and CBD in this process, then? Why are we so affected by these cannabinoids? 

It is worth knowing what happens in our brains when we merely want to scratch our nose, or do anything at all. The cells in our brain are called neurons. These cells communicate with each other and with the rest of our body by sending chemical signals. Thanks to these signals, we can speak, move, think, and do everything that makes us human. All these processes take place due to the communication between neurons. Signal transmission between two neurons occurs when chemicals called neurotransmitters are released from a transmitting neuron (a presynaptic cell); travel across a small gap between two neurons (a synapse) and attach to specific receptors located on a receiving neuron (a postsynaptic cell). It stimulates the postsynaptic neuron into action, triggering a set of events that allows the signal to be passed along. This is the usual scheme of synaptic transmission, which is responsible for the transmission of information by a nerve impulse. 

The main difficulty is that cannabinoids work differently from all other neurotransmitters, and their mechanism of interaction works “backwards”. The endocannabinoid system communicates its signals in a unique way. When the postsynaptic neuron is activated, cannabinoids which represent chemical “messengers” of the endocannabinoid system are made “on-demand” from fat cells that are already present in the neuron. After that, cannabinoids are released from the surface of the postsynaptic neuron and travel in a backward direction to the presynaptic neuron, where they attach to cannabinoid receptors located on the neuron surface. Thus, in case of cannabinoids, the postsynaptic neuron serves as a transmitter, while the presynaptic neuron fulfils the role of a receiver. In short, everything happens in the opposite way to the standard synaptic transmission. 

“Why is this difference so important?” you ask. Well, as cannabinoids act on presynaptic cells, they can control the processes happening after these cells are activated. In fact, cannabinoids work according to the “dimmer switch” principle for presynaptic neurons. Such peculiarity allows cannabinoids limiting the amount of releasing the neurotransmitter, which in turn affects how signals are sent, received and processed by the cell. 

How does THC interact with the ECS and affect our behaviour? To understand the mechanism of interaction between cannabinoids and the endocannabinoid system, you should distinguish between cannabinoids produced by your ECS and “external” cannabinoids. Today, there are many compounds defined as cannabinoids, the number of which is permanently increasing. Two categories separate these chemicals:

alphagreen endocannabinoid system
  • Endogenous. Everything with an “endo” prefix means originating inside the body. Thus, cannabinoids that represent the endogenous type are produced naturally by the body. These chemicals interact with cannabinoid receptors to regulate such basic functions as appetite, mood, sleep, pain and others. 
  • Exogenous. This group of cannabinoids include compounds that come from outside the body. Two of the most common exogenous cannabinoids found in the cannabis plant are CBD (cannabidiol) and THC (tetrahydrocannabinol). When consumed, these compounds interact with our endocannabinoid system to produce both psychological and physical effects inside our body.

In contrast to endocannabinoids, exogenous cannabinoids that you take in from consuming cannabis-infused products stay in our body for far longer periods. Intake of these compounds has the effect of activating the endocannabinoid system to a greater extent. It allows the ECS to work at a more productive rate than usual. 

So, what happens when you take THC? When a person smokes, or ingests marijuana in another way, THC “overwhelms” the endocannabinoid system by quickly attaching to cannabinoid receptors in the brain and body. Such binding interferes with the ability of natural endocannabinoids to do their usual job of fine-tuning communication between neurons and can throw the entire system off balance. Cannabinoid receptors are located in many parts of the body and brain, and this explains why THC’s effects are so wide-ranging. 

Research shows that the THC cannabinoid binds to both CB1 and CB2 receptors and has the effect of activating them in the same way as endocannabinoids would. The ability of THC to bind with both types of receptors is the secret to its power. Many people think that most of the THC effects are merely psychological, though this compound does far more than simply get us high. THC has been proven to help with diseases and conditions like asthma, nausea, chronic pain, appetite regulation, and glaucoma. In addition to this, research studying the possibility of using THC against cancer is ongoing, with promising results thus far. However, along with beneficial effects, in some cases, THC may also cause paranoia and anxiety, so it is highly recommended to consult with the cannabis specialist prior to starting to use this cannabinoid. THC also has a symbiotic effect when consumed with CBD.

Nevertheless, the THC high is a well-known effect. Why do we feel it? When this cannabinoid enters our body, it affects parts of our brain which are responsible for when we feel good, hence THC provides us with this unique bliss. Everything sounds much simpler now that we have sorted through the niceties of the mechanism of the endocannabinoid system.

As for CBD, today, cannabis experts still aren’t entirely sure how this cannabinoid interacts with the endocannabinoid system. The one thing that is known for sure is that it doesn’t bind to CB1 and CB2 receptors the way THC does. Some scientists claim that CBD works by preventing endocannabinoids from being broken down by inhibiting the FAAH enzyme. It prevents and slows down the breakdown of Anandamide which is one of the most important endocannabinoids in our body. The result of such inhibition is a build-up of Anandamide in our brain. Equally, other specialists state that this cannabinoid binds to a receptor that hasn’t been discovered yet. The details of CBD interaction with the ECS are still under debate, and it will most probably take time to come to a unanimous conclusion. Nevertheless, it was proven that CBD doesn’t cause any psychological effect and can help with a wide range of conditions, including nausea, psychosis, anxiety, inflammation, rheumatoid arthritis, PTSD, cardiovascular disease, diabetes, schizophrenia, epilepsy, neuropathic pain and muscle spasms. In addition to this, CBD potentially can be used for inhibiting tumour growth. 

What can we do to support our endocannabinoid system?

Our endocannabinoid system works with our central nervous system in order to modulate and maintain homeostasis in the body. When our body is healthy, and the ECS is operating optimally, its overall activity is usually low. However, during an immune response or increased activity of the central nervous system caused by psychological dysfunction or stress, the activity of our endocannabinoid system may change. Is it possible to upregulate the ECS and regain internal balance, then? 

alphagreen endocannabinoid system

A range of research has revealed that several classes of drugs can upregulate the endocannabinoid system. These medications include:

  • analgesics (opioids, non-steroidal anti-inflammatory drugs, glucocorticoids);
  • antipsychotics;
  • antidepressants;
  • anticonvulsants;
  • anxiolytics.

In addition to these medicines, other therapies are also used to boost the endocannabinoid system. Among them are complementary and alternative medicine (CAM) therapies, dietary supplements, acupuncture and herbal medicines. Nowadays, there are no controlled clinical trials that would prove the link between these therapies and the endocannabinoid system. However, it is suggested that the ECS is impacted by a wide range of medical interventions, including both conventional and alternative therapies. The increasing anecdotal evidence confirms this theory and triggers new studies investigating the possibility of substituting traditional medications with alternative therapies. 

As we know, the endocannabinoid system consists of the cannabinoid receptors, associated ligands, and metabolic enzymes. Cannabinoids like THC, CBD, and CBN fit into these receptors like a key in a lock and can impact a range of physiological processes affecting our memory, appetite, anti-inflammatory effects, pain modulation and other responses of our immune system. As mentioned, the primary task of the endocannabinoid system is to modulate the homeostasis in our body. The receptors of the ECS are mostly expressed in cells of our central nervous system and immune system, although they are also present in skeletal tissue, muscle cells, liver and fat. Cannabinoids act as neuromodulators for different processes, including pain sensation, appetite, and motor learning. The role of the endocannabinoid system in maintaining equilibrium within our bodies consists of five “golden rules”:

  • relax;
  • eat;
  • sleep;
  • forget;
  • protect. 

The endocannabinoid system modulates all the processes starting from embryological development, to neuroprotection and neural plasticity. The ECS is also involved in cellular processes such as apoptosis, carcinogenesis, the regulation of feeding, hunger, satiety, metabolism and pain, as well as our emotional memory. The system supports our immune system and promotes a healthy inflammatory response. 

All the disorders associated with the endocannabinoid system represent the Clinical Endocannabinoid Deficiency Syndrome (CEDS). The main reason for the onset of CEDS lies in the body’s inability to produce or utilise endocannabinoids. “CEDS” describes a certain dysfunction in the endocannabinoid system, which contributes to a general breakdown in the ability of our body to maintain internal stability, or homeostasis. Such a disruption can lead to a variety of illnesses, such as:

  • migraines;
  • fibromyalgia;
  • irritable bowel syndrome;
  • bipolar disorder;
  • schizophrenia.

Other conditions which may partly be caused by CEDS include:

  • Huntington’s disease;
  • Parkinson’s disease;
  • multiple sclerosis;
  • anorexia;
  • chronic motion sickness.

There are three different ways to address CEDS and avoid the above-mentioned health problems:

  1. By increasing the number of endocannabinoids produced by our body;
  2. By decreasing the rate at which these endocannabinoids are degraded;
  3. By increasing the number of receptors and improving their function. 

To this day, controlled clinical trials involving drugs that treat CEDS have not been held. With such a lack of human trials, we can only rely on preclinical approaches allowing us to review the available research to better understand CEDS and possible ways to influence it. Possible interventions for CEDS include:

  • already approved pharmaceutical drugs; 
  • CAM therapies;
  • unapproved investigational new drugs. 
alphagreen endocannabinoid system

Let’s consider each of these methods in detail:

Pharmaceutical drugs. Approved medications that have shown positive results in interaction with the endocannabinoid system include opiates, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs) and pain relievers such as acetaminophen. Some of the NSAIDs have shown an ability to inhibit a key enzyme which is responsible for breaking down endocannabinoids. They enhance the activity of endogenously produced cannabinoids, as well as the activity of natural and synthetic cannabinoids.

In one of the animal studies, it was demonstrated that a combination of NSAIDs with cannabinoids produces synergistic effects in which a low dose of a cannabinoid became fully activated after the administration of an NSAID pain reliever. When administering both ibuprofen and AEA, researchers achieved synergistic pain-relieving effects which were shown to involve both CB1 and CB2 types of cannabinoid receptors. In addition to this, in one study, a cannabinoid was found to reduce the number of gastric lesions produced by NSAID pain relievers.

One of the approved pharmaceutical drugs was aimed at obesity treatment. It is a proven fact that obese people have an overactive ECS, which may suggest a reduction in the ability to regulate metabolism and hunger. A drug, Rimonabant, was developed to reverse this effect by blocking the CB1 receptor and was given approval as the treatment of obesity. However, eventually, it was taken off the global market due to the serious side effects, including suicides. A new wave of research on CB1 antagonists is underway that can minimise the side effects of depression and anxiety while providing potential efficacy in treating obesity.

Another approved medication that has shown positive results in interaction with the ECS is glucocorticoids. According to some studies, the chronic administration of these drugs enhances the activity of endocannabinoids. It was also suggested that corticosteroids have a cannabimimetic component which could lead to the chronic down-regulation of the ECS. 

Antidepressant drugs such as serotonin-specific reuptake inhibitors (SSRIs), selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors (MAOIs), were believed to provide their effects by increasing the amount of the neurotransmitter serotonin. However, new evidence suggests that these antidepressant drugs may upregulate the CB1 receptor, which might result in improved mood and symptoms. 

More research is needed to investigate the whole spectrum of drugs that may interact with the ECS. Even medications that have been available on the market for many years, including some over-the-counter drugs, may have cannabimimetic activity, so a range of new studies along with the “fresh look” at old drugs are necessary. 

All other methods of improving our endocannabinoid system fall into the wide category of Complementary and Alternative Medicine therapies (CAM).

Polyunsaturated fatty acids (PUFAs) play an essential role in many cellular and multicellular processes as well as appear to help regulate the ECS. Two most common PUFA – alpha-linolenic acid (an omega-3-fatty acid) and linoleic acid (an omega-6-fatty acid) are considered critical as they cannot be produced by our body and must be obtained from foods. The deficiency of these components in our diet may influence the activity of the ECS, leading to increased pain, inflammation and swelling. Taking supplements that contain omega-3 and omega-6 fatty acids will ensure that sufficient levels of these components are present to allow proper ECS signalling. It was also shown that a constant deficit in the amount of PUFAs might cause chronically elevated endocannabinoid levels in the brain, which results in a decrease in the activity of the endocannabinoid system. An interesting fact is that similar results were also noticed in case of excess of these components. You can avoid this dysregulation by consuming enough essential fatty acids, but not in excess amounts. 

Another supplement that has been shown to beneficially interact with the ECS is a vitamin E derivative called α-tocopheryl phosphate (α-TP). α-TP doesn’t bind directly to cannabinoid receptors. Instead of this, it has been shown to modulate synaptic transmission suggesting an indirect role in the modulation of the endocannabinoid system. Foods rich in vitamin E include avocado, nuts, vegetable oils, seeds, fish and some dark leafy greens. 

Probiotics are also beneficial to the ECS and to human health in general. These symbiotic microorganisms are produced during fermentation and can be found in fermented foods like yoghurt. Probiotics were shown to increase the expression of the CB2 receptor in the cells that line our gut, which has been associated with having less pain. Probiotics also modulate CB1 receptor expression reducing it. This decrease was also associated with a decrease in the amount of fatty tissue.

Another class of compounds with reported endocannabinoid system activity is called flavonoids. In large part, flavonoids are the chemicals which give things flavour. Plants rich in flavonoids include red clover, soybeans, and camellia Sinensis. These compounds are beneficial for our ECS as they have been shown to inhibit the enzyme that breaks down cannabinoids.

It is not only pharmaceutical drugs and dietary supplements that can be used to affect the ECS. Mind-body practices are another way to influence the condition of the endocannabinoid system and keep internal balance. The link between mind-body practices and the ECS is explained by the hypothalamic-pituitary-adrenocortical (HPA) axis. Chronic stress usually increases cortisol levels at the same time, reducing 2-AG levels. An interesting fact is that in the case of repeated stress, 2-AG levels increase or decrease depending on the nature of the stress and whether it is persistent or intermittent. This ability of our brain allows people working in high-stress jobs to adapt and manage their cortisol levels despite high levels of stress. It is also a reason why some people seem to be more naturally “stress-resistant” than others. 

Alternative practices like acupuncture have also demonstrated beneficial effects on our endocannabinoid system. Acupuncture is aimed at upregulating the expression of cannabinoid receptors and works by increasing the levels of endocannabinoids in the skin. At the same time, it was shown that similar procedures like massages and body manipulation could increase endocannabinoid levels while decreasing the overall activity of the ECS.

Exercise is also an integral part of our wellbeing and ECS homeostasis. Currently, there is a lot of data demonstrating that exercises induce analgesia and sedation. However, despite years of research and studies attempting to show a neurochemical basis for these phenomena, the mechanism of these changes remains a mystery. To date, the one thing that is known for sure is that exercise of moderate-intensity activates the ECS, triggering a mechanism of exercise-induced analgesia. 

alphagreen endocannabinoid system

Bottom line

The endocannabinoid system is a universe inside us. It is both explored and under-explored at the same time. Various studies have unveiled the mystery surrounding the benefits of cannabinoids on our health. However, hundreds of questions about the ECS remain unanswered, as well as all the ways cannabinoids and other drugs interact with it and affect it. A lot of work is waiting to be done in order to thoroughly understand all the ECS’s features and peculiarities.

The endocannabinoid system plays an essential role in keeping our internal processes stable, and its importance shouldn’t be understated. With such rapid development of medical cannabis, knowledge of its interaction with our ECS on a cellular level can significantly increase the effectiveness of the cannabinoids and reduce their potential adverse side effects. In addition to this, a better understanding of the endocannabinoid system and its interaction with cannabinoids could eventually hold the key to treatment of various diseases and conditions, as well as reduce the adverse effects from other medications.

Anastasiia Myronenko

Verified by a Healthcare Professional

Anastasiia Myronenko

Anastasiia Myronenko is a Medical Physicist actively practicing in one of the leading cancer centers in Kyiv, Ukraine. She received her master’s degree in Medical Physics at Karazin Kharkiv National University and completed Biological Physics internship at GSI Helmholtz Centre for Heavy Ion Research, Germany. Anastasiia Myronenko specializes in radiation therapy and is a fellow of Ukrainian Association of Medical Physicists.

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