The endocannabinoid system, or ECS, is a complex system of cellular signaling present in all vertebrate animals and necessary for our very survival. Discovered in the 1990s while researchers were exploring THC, a well-known cannabinoid present in marijuana, the ECS is now known to be involved in several other physiological systems related to anxiety, sleep, mood, stress, appetite, memory, reproduction, inflammation, pain, thermogenesis, and heart function. Endo, meaning “in” is an important deviation from the word cannabinoid because it implies that these cannabinoids are made within the body and not obtained exogenously from a plant.
Essentially, the ECS keeps everything in balance. If you start to sweat on a hot day, it is the ECS that kicks in monitoring your internal environmental temperature and stimulates the sweating or cooling down process. It is responsible for homeostasis in the body.
The endocannabinoid system, with its complex actions in our nervous system, immune system, and various biological and behavioral systems, is literally a bridge between body and mind. By understanding this system, we can begin to explore how states of consciousness can affect health or disease.
Furthermore, recent research shows that endocannabinoids, phytocannabinoids and the ECS induce widespread or gene specific changes with the possibility of genetic transferability of changes from one generation to the next.
How a person relates to their external environment is determined by the ECS. Administration of endocannabinoids affects a person’s creativity and sharing experiences.
The ECS Tone
The ECS operates in a continuous cascade of enzymatically orchestrated pathways of which the endocannabinoids flow, attach to receptors, are degraded and synthesized as needed. This may all happen congruently in a multi-system fashion. This is called the ECS tone. ECS tone is an indication of the overall state of your ECS. Obesity, for example, represents an elevated hypothalamic endocannabinoid tone. Diabetes is another example of a dysregulated tone. The tone is the overall action generated by the receptors, endocannabinoids, and enzymes all working in sync throughout the body creating a rhythmic flow that leads to balance in the body. A lack of balance often involves a dysfunctional ECS.
How Does the ECS Work?
The ECS system is a vibrant and alive system whether you are aware of its processes or not. Endocannabinoids are produced within the body which is why we have receptors for them located in all our major organ systems. Cannabinoid receptors sit on the outside of cell monitoring for conditions both inside and outside the cellular wall to observe changes in cellular activity. Enzymes then respond to changes in cellular activity by degrading the endocannabinoids no longer needed.
When signals are received at the receptor that an endocannabinoid is needed, it is made immediately and secreted to attach to the cannabinoid receptor where it is then taken up into the cell and tells the cell how to secrete other substances like hormones or neurotransmitters such as serotonin. They affect how other messages are sent, received and processed by other cells.
There are 3 Major Components to the ECS System
- Endocannabinoid receptors
- Endocannabinoids
- Enzymes that help break down endocannabinoids
Taken together, these three components of the ECS regulatory system assure that the body remains in homeostasis with neither deficiency nor excesses of activity.
What are The Two Main Cannabinoid Receptors?
Scientists estimate that the endocannabinoid system evolved over 600 million years ago. Cannabinoid receptors are present throughout the body and are considered to be the most numerous receptor system.
Endocannabinoids are cannabinoids our body makes that bind to these receptors and phytocannabinoids are plant cannabinoids that also bind to these receptors.
The two main cannabinoid receptors most studied are CB1 and CB2. CB1 is the most abundant receptor in the brain while CB2 receptors are found outside of the nervous system such as in immune cells. The receptors act as a doorway for the cannabinoids to enter the cell. Both endocannabinoids and cannabinoids from plants can influence the CB1 and CB2 receptors.
Receptors are like locks and endocannabinoids and cannabinoids are like keys that unlocks the door and allows metabolic processes to occur. Both endocannabinoids bind to these receptors like THC does to CB1 but are produced on demand in nerve cells and travel backwards to inhibit the release of various neurotransmitters. For example, glutamate is one of the stimulatory neurotransmitters but when present in excessive concentrations such as after a stroke or head injury it can cause neuropathic pain. The endocannabinoids are naturally secreted after such an injury and act to inhibit glutamate release thus alleviating neuropathic pain. Enzymes destroy the endocannabinoids when they are no longer needed.
TRP Channels as Cannabinoid Receptors
A third receptor, TRPV1 (transient receptor potential vanilloid-one) is also considered to be part of the ECS and is a target of the body’s two main endocannabinoids, but not of THC. CBD is thought to exert many of its effects through this receptor.
Transient Receptor Proteins (TRP) are a group of membrane proteins involved in the transduction of a lot of chemical and physical stimuli, including temperature, pain, and inflammation. TRPV1 is but one of these channels that function within the ECS. There is also TRPV2, V3, V4 and V5, among others.
Growing evidence is showing that non-retrograde or communication exists within the ECS as well. Multiple points of interaction have been identified in the ECS involving communication with the TRPV1 receptors directly, called non-retrograde communication. Evidence points to CBD acting via the TRPV1 receptor in mediating some of its effects in potentially alleviating the inflammation of arthritis, for example.
What are the Two Major Endocannabinoids?
Unlike THC, endocannabinoids are produced within the body and bind to the CB1 and CB2 receptors. These two endocannabinoids are:
- Anandamide (from Sanskrit meaning “eternal bliss”)
- 2-arachidonoylglycerol (2-AG)
A unique and striking feature of these endocannabinoids is that their precursors are present in fatty membranes. Upon demand, endocannabinoids are liberated in one or two rapid enzymatic steps and released into the extracellular space. This is in direct contrast to typical neurotransmitters like serotonin which are secreted ahead of time.
The routes of synthesis and degradation of anandamide and 2-AG are distinctly different from each other.
Relationship Between THC and Endocannabinoids
These endocannabinoids are not mind-altering, addictive chemicals such as THC is. That is where so much of the public confusion comes in. THC may be similar in structure to anandamide; however, it is not the only plant-based cannabinoid being studied as having effects in the ECS system. CBD is another phytocannabinoid under scrutiny as well as the cannabinoid, CBN and other minor cannabinoids.
Relationship between THC and CBD
Cannabidiol, or CBD, is a cannabinoid under study that does not have the psychoactive effects associated with the plant-based cannabinoid THC despite having the exact same molecular structure. Cannabinoids are compounds found in the Cannabis Sativa plant of which THC and CBD are the most actively studied cannabinoids to date. CBD is the second most abundant cannabinoid after THC in the cannabis plant. In addition, a total of 8 other major ones have been identified with a total of over 100 cannabinoids confirmed to date. Many of these minor cannabinoids exert an effect of their own that synergistically interacts with the other cannabinoids creating an entourage, or synergistic effect.
Why the Endocannabinoid System is Important
The endocannabinoid system has several beneficial effects.
These include:
- Pain Relieving Effects
- Cancer Fighting Properties
- Prevention of Neurodegenerative Diseases
- Promotion of Good Health
The ECS assures that the immune system and the central nervous system are in balance and healthy. Endocannabinoids play a key role in the removal of old memories aiding post traumatic stress survivors as well as conditions related to chronic anxiety.
The ECS aides in the regulation and transfer of energy from foods thus aiding the digestive tract and utilization of foods consumed.
ECS helps boost immune system cells, plays a role in inflammation reduction and in the control of neurological disorders.
How Do Endocannabinoids Work?
Essential fatty acids, chocolate, herbs, spices, and tea can naturally stimulate the ECS. A healthy ratio of omega-3 and omega-6 fatty acids can enhance the activity of the ECS. Endocannabinoids are produced from arachidonic acid, an omega-6 fatty acid.
Endocannabinoid release occurs immediately after bodily biosynthesis with no intermediate storage for “later use” making them ideal homeostatic modulators in real-time. This is seen, for example, in appetite regulation. Endocannabinoids regulate appetite and food intake through stimulation of the CB1 receptors which stimulate the release of hunger/satiety hormones. This all happens relatively rapidly with little thought; it is just an occurrence of “balance” between hunger and satiety. Achieving and maintaining energy balance is the objective in this respect.
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The Role of Enzymes
Metabolic enzymes that break down the endocannabinoids after they are used are important for maintaining the homeostasis. Two primary enzymes have been isolated that are charged with this duty:
- Fatty acid amide hydrolase or FAAH
- Monoacylglycerol acid lipase (MAGL)
FAAH breaks down anandamide and MAGL breaks down 2-AG. These enzymes guarantee that endocannabinoids are used for as long as needed and no longer. This is a distinguishing factor of these enzymes from the actions of hormones or other regulating signals like neurotransmitters which can persist for seconds, minutes or packaged and stored for later use.
These enzymes cannot break down plant-based cannabinoids, a limiting factor in cannabinoid research relative to disease treatment. This means that if an active dose of cannabinoids is found for an illness the exact dosage must be determined because the natural homeostatic mechanisms of the ECS will not be able to regulate cannabinoids administered from the plant.
Endocannabinoid Deficiency
As we learn more about the ECS we are discovering diseases that may be classified as endocannabinoid deficiency diseases. Medical science has termed these clinical endocannabinoid deficiency dysregulation diseases or CECD for short. Available evidence seems to indicate that the ECS system suffers from a deficiency of anandamide, thus giving the idea that treatment of the ECS to upregulate the tone might benefit these disorders.
These conditions include:
- Fibromyalgia
- Migraine
- Irritable bowel syndrome
- Dysmenorrhea
- PTSD
- Bipolar disorder
The conditions listed frequently involve more than one physiological system and effective treatment for them has been difficult to unearth. It is only logical that science would look to multisystem treatment modalities such as cannabis to treat multisystem disorders such as the ones just mentioned.
How Does THC Interact With the ECS?
THC interacts with ECS in the same manner as the endocannabinoids do. It can bind to either CB1 or CB2 receptors and is not subject to enzymatic regulation, thus the problem with addiction and mind alteration. On the other hand, it may help with pain and stimulate the appetite for those who have lost theirs as in cases of anorexia.
How Does CBD Interact With the ECS?
CBD is a different story. CBD does not make you “high” and does not carry any negative side-effects such as paranoia or delusions. Experts don’t exactly agree on how CBD does work or even exactly what it does, but they hypothesize that it prevents endocannabinoids from being broken down through the effects of the enzymes. Scientists do know that CBD does not bind to the CB1 or CB2 receptors in the same manner as THC. Science has proven that CBD prevents the enzyme FAAH from breaking down endocannabinoids, unlike THC where enzymes have no effect.
The ECS is the key to our body maintaining homeostasis. It may one day hold the answers to treatments of diseases that affect multiple organ systems for which we have no treatments. The ECS offers a rich landmine of untapped research and potential therapeutic applications.
Concluding Remarks
We need to further educate others on the important role of the ECS, on cannabinoids and the differences between THC and CBD. Along with more research, we need to keep an open mind as to the application of cannabinoids to therapeutic treatments of multi-system disorders for which we currently have no well-defined treatment protocols.
And, keep in mind that lifestyle activities can alter endocannabinoid tone, and thus, ECS activity. Research has shown that diet, supplements, herbs, weight control, and exercise also modulate the ECS tone. Clinical trials investigating these modalities are sorely lacking and in need of attention.
In conclusion, the ECS may be a newly discovered system, but is old in its presence and seemingly imperative to our existence. Furthermore, the field of pharmacology is now considering all members of the ECS as potential novel therapeutic targets for the modulation of problematic diseases. The discovery of the ECS opened a doorway of discovery of possible novel therapeutic agents that can be utilized in the form of cannabinoids or related chemical structures to modulate health and disease without the adverse side-effects so often associated with the psychoactive cannabinoid, THC.
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