The endocannabinoid system (ECS) has an extremely important survival role in our body. It has a critical ability to maintain the body’s homeostasis, including our brain, endocrine and immune system among others. ECS is a unique system in many ways. It is the primary body regulator and has a wide range of effects due to abundance of cannabinoid receptors located everywhere, from immune cells to neurons. Cannabis can play a special part in this as its natural cannabinoids are very similar to our body’s endocannabinoids and bind exceptionally to our body processes. Another advantage is that cannabinoids are quickly synthesized and decomposed as well, and larger amounts do not stay in the body for long. This presents a great potential for cannabinoid therapies, as a safer alternative to opioids and benzodiazepines.
Many have heard of some systems in our body such as sympathetic nervous system responsible for “fight” or “run” function. However, less people are familiar with the endocannabinoid system, which is critical for almost every part of our being in every moment.
Important Role
Endocannabinoid system is widespread neuromodular system that plays an important role in development of the central nervous system, synaptic plasticity, and response to endogenous (internal) and outside factors. It’s a complicated system that was discovered by researchers in the 90s while researching a well-known cannabinoid THC. ECS mitigates and controls many of our most critical body functions such as learning and memory, emotion processing, sleep, temperature regulation, pain mitigation, inflammatory and immune response, and appetite. Currently, ECS is in the center of attention of international research and drug development.
Endocannabinoid system includes a wide chemical signals and cell receptors network, which are densely located in the brain and body. It is comprised of cannabinoid receptors, endocannabinoids, and enzymes, responsible for synthesis and decomposition of endocannabinoids. External cannabinoids (example, tetrahydrocannabinol or THC) have a biological effect while interacting with cannabinoid receptors. The most studied and well-known endocannabinoids are 2-AG and Anandamide.
Experts are still trying to fully comprehend the ECS. Until today, they can confirm it plays a major role in regulation of many functions and processes including:
Endocannabinoid system is present and active in our body even if we do not consume cannabis and is very accurate. For example, if our body temperature changes outside of normal, ECS regulates it without changing other processes. When it helps the body get back in optimal state, enzymes decompose the cannabinoids / endocannabinoids and prevent potential over involvement.
To fully understand how ECS works we will segment it and explain how it works, why it is important and how it interacts with cannabis.
CANNABINOID RECEPTORS
We can find cannabinoid receptors throughout our bodies. Cannabinoids and endocannabinoids bind to them and signalize ECS to act. There are many more cannabinoid receptors in the brain compared to other types of receptors. They act as traffic police and control the levels and activity of most of the other neurotransmitters. They regulate activity with immediate response, increasing or decreasing the activity of a system that needs to be adjusted. This can be hunger, temperature, focus, and many others.
There are 2 main identified cannabinoid receptors:
- CB1 receptor, which is densely present in the brain and central nervous system (hippocampus, amygdala, hypothalamus…)
- CB2 receptor, which is mostly located in the peripheral nervous system, especially in the immune cells.
Endocannabinoids and cannabinoids can bind to both receptors. Effects depend on where the receptor is located, and which cannabinoid or endocannabinoid binds to them. For example, cannabinoids can target CB1 receptor in the spinal nerve to mitigate pain. Others can bind to CB2 receptor in the immune cells and communicate there is inflammation in the body, which is a common sign of autoimmune conditions.
In endocannabinoid effects CB1 and CB2 cannabinoid receptors are the main mediators. Both receptors are connected to G-protein.
ENDOCANNABINOIDS
Endocannabinoid or endogenous (internal) cannabinoids are molecules produced by our body, which are similar to cannabinoids. They are completely naturally produced in our body and are lipid-based neurotransmitters that stimulate cannabinoid receptors. Experts have been able to identify two main endocannabinoids:
- Anandamide (AEA) and
- 2-arachidonoylglycerol (2-AG)
Anandamide got its name after Sanskrit word “ananda”, which means bliss. Both endocannabinoids help with optimizing internal functions. Body produces them when required and due to this it is very hard to define the typical level. The body produces them automatically. They are present in different organs and tissues such as muscles, brain, and cells. Endocannabinoids are activated when binding to cannabinoid receptor. The receptors are also located across the body.
ENZYMES
Enzymes are responsible for decomposition of endocannabinoids after they finish their function. Two main enzymes are responsible for this process.
- Fatty acid amide hydrolase (FAAH), which decomposes AEA and
- Monoacylglycerol acid lipase (MAGL), which usually decomposes 2-AG.
CANNABIS AND THE ENDOCANNABINOID SYSTEM
Due to cannabis cannabinoids similarity to endocannabinoids, it is strongly connected with the endocannabinoid system. Due to this fact, various combinations of cannabinoids can profoundly help to balance our body.
THC and ECS Interaction
Tetrahydrocannabinol (THC) is one of the main cannabinoids found in cannabis. When it enters the body, it binds to receptors similar to endocannabinoids. In part it is very influential as it can bind to both types of receptors. This allows it to produce various effects on the body and mind (some are more welcomed than others). For example, THC can help us with pain mitigation and appetite stimulation. On the other hand, in some cases it can cause paranoia and anxiety (usually at higher dosages).
CBD and ECS Interaction
The second main cannabinoid in cannabis is cannabidiol (CBD). Contrary to THC, CBD does not have psychoactive effects and usually no side effects. CBD does not bind to receptors in a way that THC does. Many experts believe that it prevents decomposition of endocannabinoids and with it enables a greater effect. Others believe we are still to discover a new receptor to which it binds.
When using cannabis, the best results are usually achieved by using full spectrum products that offer the “entourage” effect. You can read more about it here. There are multiple types of products which are also used in different ways. For internal conditions CBD oil or resin is used most often. For treating skin conditions, the most common options are CBD creams or similar. The end result is very much dependent on the products quality.
ENDOCANNABINOID SYSTEM FUNCTIONS AND HOMEOSTASIS
Endocannabinoid system is complex and new research on its potential functions are emerging one after another. Current research connects the endocannabinoid system with the following brain and body functions:
- Appetite and digestion,
- metabolism,
- chronic pain,
- inflammation and other immune responses,
- mood,
- learning and memory,
- motor function control,
- sleep,
- cardiovascular function,
- muscle formation,
- bone transformation and growth,
- liver function,
- reproductive system function,
- stress,
- skin and nerve function.
All of the mentioned body functions contribute to homeostasis, which refer to stability of our internal environment. For example, if external factors such as pain due to injury or fever shake our homeostasis, ECS is activated and helps our body return to the optimal state. Nowadays, experts also believe this is the core function of ECS.
How to Maintain Homeostasis?
Among all the complex cells signaling, genetic mutations, and external threats, how do we maintain our homeostasis? The answer is the endocannabinoid system. It is present in most of our body and keeps the body in homeostatic condition. It achieves this state with a negative backward loop, which functions with the activation of post-synaptic neurons that synthesize and release the endocannabinoids and target different cannabinoid receptors. While other cells have signal modifiers that can enhance or redirect signals, the neuron overwrites all these cells. For example, toe fracture would result in cellular death. Lymph response would increase the blood flow and migration of the white blood cells to the critical area. ECS would then recognize the excessive lymph signals and when it decides there is no more need for increased inflammation, cannabinoid receptors in the surrounding immune cells and tissue would start to bind with cannabinoids and slowly reducing the inflammatory response.
Similar process goes on with pain signals in our brain. Binding and stimulation of CB1 receptors will increase the gamma-aminobutyric acid neurotransmitters (GABA) and consequently decrease the pain signals through the brain. Because cannabinoids affect the presynaptic cells, they can control what happens when the cells are activated. In general, cannabinoids work as a “dimming switch” for presynaptic neurons. They limit the quantity of released neurotransmitters (expl. dopamine), which affects the way of sending, receiving, and processing cell messages.
ENDOCANNABINOID DEFICIENCY
Some experts firmly believe in the theory known as Clinical Endocannabinoid Deficiency (CECD). This theory suggests that low endocannabinoid levels in our body or non-optimal ECS can cause certain medical conditions to develop in our body.
In a 2016 article, an analysis of more than 10 years of research on this topic was conducted. It suggests that it could explain why some people develop migraines, fibromyalgia, irritable bowel syndrome, and others. None of these conditions has a clear sign of origin. Furthermore, conditions like these are commonly resistant to therapy and occur simultaneously. If CECD theory is involved in these conditions, focusing on ECS or endocannabinoid production might be the missing link to treating them. However, more research is required in this area before clear solutions can be proposed.
THE ROLE OF ENDOCANNABINOID SYSTEM IN LEARNING AND MEMORY
Due to many research we know for a fact that ECS has a critical role when it comes to learning and memory. The most obvious sign is that one of the main side effects of using high dosage recreational cannabis (higher THC levels) can be a temporary short term memory disorder. When the effects are no longer present, the memory comes back. Furthermore, complex studies on human response to THC and the ability of short-term memory have been conducted. Samples gathered with fMRI have also been observed.
Scientist and author of a popular book “The Botany of Desire”, Michael Pollan claims, that cannabis is one of the plants people cultivated and developed with for thousands of years. Partly it is due to the fact that forgetting has an important role for our brain not to be overwhelmed by the abundance of sensorics data. Pollan claims that if we would not forget, we could no function and cannabis help us with this. The role of ECS with forgetting also opens up opportunities of treating PTSD. It’s a condition where we cannot remove intrusive, unpleasant memories from our mind. They can cause a syndrome with problematic and dangerous symptoms connected with pathological memory.
RESEARCH AND NEW WAYS OF USE
It is a fact that endocannabinoid system is one of the most important discoveries in the field of human body. However, we require many more years of research to fully comprehend the full potential of so complex, diverse, and extensive system. With the decrease of legislative barriers in some countries started conducting various research of ECS and how cannabis affects it. In the past people knew the amazing effect of cannabis on the human body. Today we have an opportunity to understand the science behind these effects. Why and how do these effects that we can sense happen? For better and healthier future, we hope that knowledge will expand, and cannabis will reach its well-deserved place in our society.
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G. D. C.
02. 11. 2021
