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Cannabinoids and the eCS
What it is, what it isn't

About the Endocannabinoid System (eCS)

What is the eCS?

The eCS (endocannabinoid system) is unlike other body systems; it isn’t made up of specific organs. The eCS is present in the cells of all the organs of every other body system. The three parts of the eCS are found on nearly all the cells of the body. The separate eCS parts are so small can only be seen with a powerful microscope. The 3 parts are: 1) endocannabinoid neurotransmitters (AEA, 2-AG, PEA, OEA and others); 2) enzymes that build and break down the after the signal is sent) endocannabinoids (e.g., FAAH, MAGL) 3) the cannabinoid receptors (CB1, CB2, CB3, GPR119 ).

Using signals, the parts of the eCS work together regulating the body’s dynamic balance or ‘homeostasis;. The properly functioning eCS insures all the jobs your body must perform are being done. Among its many important functions, the eCS maintains balance of the body’s immune response. This function reduces chronic inflammation and resulting tissue damage leading to less age-related discomfort. However, stresses of life and aging wear down the eCS, causing loss of quality or tone.

When the eCS doesn’t have a strong tone, it is less able to maintain balance. Inefficient homeostasis can result in development of conditions such as overactive immune response. When eCS tone is low, Inflammation cannot be maintained in a balanced immune response. This condition can lead to chronic inflammation causing damage to the body. Chronic inflammation leads to tissue damage and pain. Low eCS tone over the lifespan yields age-related discomfort in people and companion animals. Supplementation with cannabinoids such as PEA restores a strong eCS tone. A strong or robust eCS tone restores the eCS’s ability to maintain homeostasis. Over the lifespan, reduced chronic inflammation means reduced age-related discomfort.


Below are four links to help explain this. Please be aware that you will be leaving the PMI website if you select any of these links. You are, of course, welcome to return at any time.
1. Signaling at the Synapse – This explains how the signaling works at the lowest level of a cell.
2. Inflammation & Tissue Injury – This explains how the immune system is signaled to attack invading bacteria, viruses abrasions and cuts to tissues, etc. It is the job of the immune system to send its warrior cells to the place of ‘injury threat’. This process is called the inflammatory response. It should last only as long as the threat exists. The eCS will signal the immune system to stop its attack when appropriate. When the eCS is not fully functioning, the inflammatory response may last longer than necessary. This may result in chronic inflammation leading to chronic tissue damage and therefore chronic pain.
3. Stimulating the eCS – This presentation shows how how different parts of the brain and body include the eCS and how it functions in different parts of the organism.
4. The eCS in the Skin – The skin is our main defense against the outside world that is filled with constant dangers to our wellbeing. Because of its major importance to our survival, the skin has its own eCS as well as its own immune system.


Again, the eCS regulates homeostasis, the process keeping all biochemical reactions in balance. This extensive body/brain wide eCS requires robust performance or tone to maintain efficient homeostasis. When homeostasis is disrupted, negative health conditions result. Chronic inflammation, a far from homeostasis condition, occurs when eCS functioning or eCS tone is not robust. Low eCS tone is responsible for chronic conditions such as arthritic pain and other age related discomforts. A robust ‘eCS tone’ is required for lifespan animal and human wellness.

The endoCannabinoid System (eCS) is a relatively recent medical discovery with proven implications for lifespan wellness. Early evolutionarily emergence and preservation of the eCS in all mammals indicates its biological importance. Endocannabinoids (eCBs) are natural neurotransmitters regulating virtually all biological signaling in the mammalian body. eCBs signal receptors to increase or decrease activity in order to maintain homeostasis or balance. The eCS is the master regulator of homeostasis that keeps everything in balance. eCBs signal the immune system to fight problems and when to restore the resting state. The eCS signals the immune system to fight infection and to stop when it’s gone. Natural ‘endo’ (PEA) and plant based ‘phyto’  Cannabinoids, through the eCS, regulate physiological processes. These processes include biochemical reactions controlling temperature, mood, appetite and the immune system. They also influence fertility, pregnancy, immune system activity (inflammation), appetite, pain-sensation, mood, memory, etc.

Again, the eCS regulates homeostasis, the process keeping all biochemical reactions in balance. For example, chronic inflammation occurs when eCS functioning – or eCS tone – is not robust. A robust ‘eCS tone’ is required for lifespan animal and human wellness.


Cannabinoids are a class of chemical central to protecting both plants and animals, although through different routes. Some cannabinoids are found in virtually all Cannabis plants. These are known as phyto cannabinoids (from plants). Some cannabinoids are special to specific plants such as the two most familiar cannabinoids found in cannabis: Cannabidiol (CBD) and TetraHydroCannabinol (THC).

Different Cannabinoids are natural to mammals. These are known as endoCannabinoids (or inside) the animal. All cannabinoids are able to interact with special mammal receptors known as CB1, CB2 and CB3. Cannabinoids may or may not connect directly with these receptors. Rather they seem to influence these receptors through interactions involving various cannabinoids and other chemicals including terpenes (also from plants) through a process known as the entourage effect. This enables combinations of cannabinoids to perform better than individual cannabinoids by themselves.



Cannabidiol (CBD), a natural plant-based or phyto Cannabinoid molecule produced from the Cannabis plant genus. Cannabis includes both Hemp and Marijuana plants distinguished by the amount of THC they produce. Cannabis plants produce a unique family of terpeno-phenolic compounds called cannabinoids. Of 450 chemical constituents known in the cannabis plant, included about 100+ different cannabinoids. The two cannabinoids usually produced in greatest abundance are cannabidiol (CBD) and/or tetrahydrocannabinol (THC), but only THC is psychoactive. NIH holds a patent on CBD as an anti-oxidant and anti-inflammatory compound. Safe, non-addictive CBD is among 100+ Cannabis-derived cannabinoids…many common to all plants. Other chemical molecules including terpenes and flavonoids are natural components of Cannabis and other plants.     THC (TetraHydroCannabinol) is the only sister cannabinoid to CBD that can make you high. CBD is the natural anti-anxiety antidote to THC and can never make anyone high.


FDA remains the key roadblock to CBD legalization. First, FDA has not scientifically determined the safety of cannabidiol due to previous research prohibitions. That means that FDA is not able to regulate its safety labeling; Commercial CBD vendors aren’t required to meet safety labeling standards that all other produce must. But, in 2018, FDA approved CBD as a drug called Epidiolex for severe pediatric seizures. Any CBD medical or health claims require FDA approved clinical trials for each indication.


CBD Product Safety: Caveat Emptor! “Let The Buyer Beware”……its an unregulated Wild West marketplace!

Regulated product safety labeling of every batch is how FDA regulates the food supply. While legal, CBD product labeling is currently unregulated by the FDA. In fact, there are no FDA labeling requirements for any CBD products. Without FDA regulations, there’s no assurance any CBD product is safe or as advertised. While some suppliers do follow FDA style safety testing for identity, potency and purity. Most do not as various random testing of products has demonstrated. There are many potential health hazards associated with cannabis farming. Only rigorous testing at the point of packaging of every batch can determine product safety.


Cannabinoid receptors are expressed in all mammals – humans and companion animals. Named after plant cannabinoids, the eCS includes specialized cannabinoid receptors (CB1 & CB2) throughout the body. endoCannabinoids (eCBs) are produced on demand from available chemicals naturally found in cell membranes and tissues. eCBs are immediately broken back down by special enzymes present within cells. Both cCB receptors are located throughout all areas of the brain and body. CB1 is predominant in the brain and central nervous system. CB2 is predominant in the immune system and most everywhere else throughout the peripheral body. Neurologist Ethan Russo, MD recognized that ‘homeostasis’ – continuous balancing of all biochemical reactions – is essential to wellness.

Because cannabinoid receptors are located on virtually all cells, Cannabinoids influence many seemingly unrelated disorders.

Natural endo-cannabinoids Anandamide (ANA) & 2-Arachidonoylglycerol (2-AG) were discovered through CBD evaluation. CBD/THC effect the homeostasis process as the body’s own ANA & 2-AG eCB analogs. ANA & 2-AG activate the same CB1/CB2 receptors that CBD and THC do.


PalmitoylEthanolAmide (PEA) is a natural endocannabinoid profoundly influencing the eCS through the CB2 and CB3 receptors. PEA, not Cannabis-derived, has exceptional wellness properties, is a ‘generally recognized as safe’ nutraceutical.
Special enzymes instantaneously produce short lived endoCannabinoids (ANA, 2AG and PEA) or eCBs, along with their enzymes and receptors, working robustly together, to maintain a robust ‘eCS Tone’. Wellness is the state of being were homeostasis is in good operating condition. When processes are out of balance, when homeostasis is not in good operating condition is when illness occurs.


When eCBs, their enzymes and receptors (eCS) perform robustly they exhibit a robust ‘eCS Tone’.

eCS Tone indicates how effectively homeostasis is maintained. When homeostasis is disrupted for long periods, it is an opportunity for illnesses to develop. Neurologist, Dr. Ethan Russo, MD, found stresses of living and aging lower eCS efficiency or eCS Tone. He identified the condition of Clinical Endocannabinoid Deficiency (CECD) as a cause of migraines, fibromyalgia and Crohn’s’ disease’ among other conditions still being investigated. Russo also discovered that cannabinoid supplementation can return the eCS to its youthful strength. In fact, Cannabinoid supplementation is recommended to maintain a robust eCS Tone throughout the lifespan. A little daily cannabinoid supplementation goes a long way toward maintaining homeostasis, keeping inflammation under control and addressing lifespan wellness including age-related discomfort.


Terpenes protect all plants from natural enemies like viruses, bacteria, bugs, etc. Cannabis includes hundreds of other chemical compounds from terpenes to essential essential oils. Dr Russo reported “terpenes (and cannabinoids) can increase blood flow, cortical activity, and kill respiratory pathogens. Cannabinoid-terpenoid interactions…produce synergy controlling pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, etc.” Consider the range of a key property of some terpenes found in full spectrum CBD oil. Typical are Mercene (antibiotic), Linalool (anti-cancer), Humulene (anti-inflammatory), Pinene (analgesic), lemalool (anti-siezure), etc.


Studies show PEA also has clinical potency in the eCS. Cannabinoids work synergistically with various cannabinoid/terpenoid and other compounds to produce an ‘entourage effect’.

The entourage effect enhances eCS effectiveness in homeostasis regulation and as a powerful anti-inflammatory including the brain while promoting lifespan wellness.


All mammals have an eCS so we can say Cannabinoids help humans as well as pets. Animal caregivers have been using cannabis for their dogs, cats, and horses since before 1996. Observed benefits include anxiety reduction, pain relief, improved mobility in arthritic animals and tumor reduction, among others. Pet Cannabinoid benefits depend on many factors including dosage, animal size, metabolism, condition severity, etc. Benefits relate to breed diversity (genetics), density and distribution of the eCS among species members. Species differences exist in the location of cannabinoid receptors within the eCS.

In the human brain, CB1 is low in areas controlling vital functions such as breathing and heartbeat. This safety profile in humans is why it’s nearly impossible to overdose on THC. Unlike opioids, it explains why overdosing on THC does not result in death. This is not true for canines and why only trace amounts of THC is advised. Cannabinoids interact with mitochondrial membrane receptors inside the cell to influence pro-apoptotic (suicidal) mechanisms in cancer cells. This is one way the immune system controls runaway cancer growth in all mammals. Cannabinoid research into canine cancers is important because 25% of all canine deaths are cancer related ( more in later years of life.) Using Authenticated Pet cannabinoid products, for example products including PalmitoylEthanolAmide (PEA) all insure cannabinoid identity, potency and purity. 


PMI’s recommends that any pet CBD product be Authenticated by a certified independent laboratory and are modeled on FDA safety standards. Until FDA regulates CBD labeling, PMI suggests your pet cannabinoid supplier assures label safety assurance of product identity, potency and purity of every batch. Look for a QR code the provides batch testing for a full spectrum certificate of analysis.


PMI is following development of new all natural approaches to anti-inflammatory compositions that utilize the eCS, i.e., PEA, but that completely avoids any involvement with Cannabis.