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 mood, stress, appetite, memory, reproduction, inflammation, sleep, pain, thermogenesis, heart function, and anxiety. 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, it 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. This puts a sense of permanency to changes that occur because of the ECS. 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 three major components to the ECS system.
Taken together, these three components of the ECS regulatory system ensure that the body remains in homeostasis with neither deficiency nor excess 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 bind to the CB1 and CB2 receptors. Receptors are like locks, and THC is like a key 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 backward 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. A third receptor, TRPV1 or transient receptor potential vanilloid-one, is also considered part of the ECS and targets the body’s two main endocannabinoids but not THC. Growing evidence shows that non-retrograde communication exists within the ECS. Multiple points of interaction have been identified in the ECS involving the TRPV1 receptor. Evidence points to CBD acting via the TRPV1 receptor in mediating some of its effects in potentially alleviating the inflammation of arthritis. 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. 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. Relationship Between THC and CBD Cannabidiol, or CBD, is another cannabinoid under study that does not have the psychoactive effects associated with the plant-based cannabinoid THC. 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 confirmed to date. How Do Endocannabinoids Work?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. Homeostasis. Balance. The role of enzymes Metabolic enzymes that break down the endocannabinoids after they are used are important for maintaining 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 or minutes or be 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 discover diseases that may be classified as endocannabinoid deficiency diseases. Medical science has termed these clinical endocannabinoid deficiency dysregulation diseases, or CECD for short. The available evidence seems to indicate that the ECS systems suffer from a deficiency of anandamide, thus suggesting that treatment of the ECS to upregulate the tone might benefit these disorders. These conditions include:
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 of those who have lost theirs, as in cases of anorexia. How Does CBD Interact With the ECS? CBD is a different story. CBD doesn’t make you “high” and doesn’t carry any negative side effects such as paranoia or delusions. Experts don’t exactly agree on how CBD works 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 doesn’t 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 cannabinoids, unlike THC, where enzymes have no effect. The ECS is the key to maintaining homeostasis in our body. It may one day hold the answers to treatments for 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 it 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 to the 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. Keywords: endocannabinoid system, anandamide, 2-AG, ECS, endocannabinoid deficiency, cannabinoid receptors
0 Comments
Leave a Reply. |
Author
|