Definitions PEA (N-palmitoylethanolamide): An endogenous fatty acid amide synthesized and metabolized by cells that binds to cell receptors. It influences a multitude of physiological functions and has potent anti-inflammatory and pain-relieving properties. Endocannabinoid System: A lipid communication network that has critical physiological functions and serves a vital purpose for our health and well-being through signaling processes, homeostasis and hormone regulation. Lipids and the ECS In 1929, scientists George Oswald Burr and his wife, Mildred Burr, discovered that omega 6 fatty acids were essential for health. This kicked off science’s interest into lipids, and by the 1960s a new age of lipid
The endocannabinoid system (ECS) is another level of security, a defence system that the body layers onto the existing security organization that is keeping us safe, whilst making sure checks and balances are in place.
The ECS is a vast signalling network that communicates with other well-known systems including the nervous, immune, hormonal or the endocrine, and other networks, but also some that are rather more obscure, like the lymphatic or the enteric nervous system sometimes called the “second brain”.
The ECS’s job is relaying important and timely information between these systems, but it also primes and prepares the body whenever danger arises. When called upon the ECS springs into action and further protects, helps repair, and lessens body blows with deft and skill.
It responds to various insults such as injury, chronic inflammation, all forms of pain, infections (whether bacterial or viral) as well as safeguarding fragile assets, like the mitochondria and nerve cells, which are highly prone to damage. In addition, the ECS keeps alert against other toxic insults, including carcinogens, solvents, UV light, pesticides.
Where is the Endocannabinoid System (ECS)?
The ECS is distributed all over the body. In its original definition, consisted of two cannabinoid receptors, CB1 and CB2, two signalling messengers (called endocannabinoids or EC’s) made by the body, called anandamide (AEA), and 2-acyl glycerol (2-AG), as well as the enzymes responsible for their synthesis (NAPE-PLD and NAT), and their breakdown (FAAH and NAAA). The receptors are differentially distributed with CB1 being primarily located in the brain, and the CB2 receptors located in close proximity of the immune system. However, as the scientists later discovered there is a significant overlap with the CB1 receptor found outside the brain, and the CB2 receptors also found within the brain.
In time, researchers discovered many other “players” that were part of the ECS, especially other receptors including GPR55, GPR119 and the ion channel receptor TRPV1 through which pain is mediated. It was also found that the receptor PPAR-alpha, which is located in the nucleus of the cells, and takes part in regulating genes associated with pain and inflammation, was also part of the ECS.
In addition, other EC’s were discovered like PEA, OEA and SEA. Eventually, scientists expanded these new discoveries to a more encompassing definition termed endocannabinoidome which correctly captures the current state of research affairs.
What Activates the Endocannabinoid System (ECS)?
When harmful triggers like inflammation and injury act on the body, the ECS activates production of EC’s like AEA, 2-AG and PEA from the membranes of cells in the vicinity of the injury. EC’s are produced on demand whenever the body requires their services. The advantage is that EC’s can be produced quickly, locally and efficiently. However, exogenous molecules that are not produced by the body can also stimulate the cannabinoid receptors CB1 and CB2. The most famous are the major actives from the hemp and marijuana varieties of the cannabis plant.
THC and CBD are the most popular but there are hundred or so other cannabinoids capable of acting on the Endocannabinoid System (ECS). THC, typically preferentially activates CB1 receptors mainly located in the brain, and thus produces the psychotropic “high”, while CBD only acts on CB2 receptors which are mainly located outside the brain. However, there are other plant species that also produce cannabis-like effects or cannabimimetic effects and some of these are the alkyl amides from the Echinacea species, beta caryophyllene from clove, oregano, black pepper and other terpene fractions like limonene, linalool, pinene, myarcene and many others. All these activate the ECS to varying degrees.
What is the Entourage Effect?
The “entourage effect” is the enhancement of a biological effect by another molecule through various mechanisms. For example, it is commonly known that pure THC or CBD are not as effective as the whole plant extract that contains CBD, THC and the many other components mentioned earlier. These other components, such as terpenes, assist in the action of THC or CBD.
The mechanism of the entourage effect is really several mechanisms that either prevent the breakdown of the ECs, improve the binding on the receptor, activate other receptors, or open up other channels that ultimately cause a greater effect of the major molecule (e.g., THC or CBD).
What are the Advantages of ECs Over Phytocannabinoids?
ECs have significant advantages over exogenous or foreign cannabinoids like the phytocannabinoids. For one, ECs are locally produced. They are molecules the body recognizes and is familiar with. The amount the body produces is exactly to the demand and the dose is well known. Further, these molecules act fast because they are locally produced. And, once they have performed their service, they are quickly broken down by the body. Phytocannabinoids, on the other hand, are not native to the body and their action requires some time for action. Moreover, their doses are not well known. For example, CBD is gaining popularity, but the effective dose varies greatly between individuals; anywhere from 20 mg to 1200 mg or more. This makes determining the right dose a challenge. In addition, the effect of CBD varies greatly in people. Finally, phytocannabinoids can and do produce adverse effects and can linger in the body and in some cases, such as THC, there is a chance of dependency. We are learning more and more about the ECS, this versatile built-in defence system that exists in all species. Our bodies rely a great deal upon this vast and remarkable network to protect and heal us from many dangers.