Understand Your Medicine: The Endocannabinoid System Part 1

P.A. Murphy
Understand Your Medicine: The Endocannabinoid System

In my last article, I gave a brief glimpse into the history behind medicinal cannabis research and its role in the discovery of the Endocannabinoid System (ECS). This week, I'll be expounding a bit on what's been learned so far about these complex networks and their role in overall health and wellness.

The ECS is made up of three distinct parts: the cannabinoid receptors which are located throughout the body (which are also made on demand as they are needed), the endocannabinoids which are made on demand specifically for those receptors, and the enzymes which break the endocannabinoids down. All three exist and work together in mammalian biology regulating various physiological and cognitive processes to achieve homeostasis (a state of optimal balance). Basically, the ECS is an internal fine tuning mechanism for health and wellness that does some pretty incredible things all on its own, when it's working properly.

The cannabinoid receptors perform different tasks depending upon the type of receptor and their location in the body. Because the receptors can be made on demand as needed, the expression (or quantity) of receptors in any given organ or tissue is unique in every individual. This means each and every person has different concentrations of receptors in different areas throughout their bodies, which is one of the reasons working with cannabis medication can be such a frustratingly slow process. Variations in expressions of cannabinoid receptors between different people causes variations in experiences with cannabis, even when consuming the exact same types of cannabis. And, since the expression of receptors can change in an individual, experiences can (and often do) deviate with those changes.

The most abundant cannabinoid receptors in the human body, the CB1 receptors, are prolific throughout the brain and central nervous system, but are also found in the digestive tract, liver, lungs, kidneys, pituitary and thyroid glands. These receptors regulate memory, mood, motor control, neurological functions, and perceptions of pain. Both the endocannabinoid anandamide (AEA) and the phytocannabinoid tetrahydrocannabinol (THC) have the greatest affinity for, and a molecular shape perfectly designed to fit, CB1 receptors. AEA, also known as the "bliss" molecule, doesn't have the psychoactive "high" of THC, but it is responsible for battling anxiety and depression, creating new nerve cells, helping to forget unnecessary details and/or traumatic events, improving feelings of happiness, and rewarding us for a job well done. Its effects are usually short lived because of the fatty acid amide hydrolase (FAAH) enzyme which breaks AEA down fairly quickly into ethanolamine and arachidonic acid. Unlike AEA, the FAAH enzyme doesn't work so well at breaking down THC, so the "high" of THC last a great deal longer than the "bliss" of AEA.

Though the CB2 receptors have a much lower expression throughout the human body than the CB1 receptors, that doesn't mean they have a less important role in the ECS. CB2 receptors are primarily found in the peripheral organs, in particular tissues associated with bone marrow, the gastrointestinal tract,the immune system, spleen, tonsils, and thymus glands and also in much lower amounts in the central nervous system. These receptors are primarily responsible for regulating cytokine (a category of small proteins important in cell signalling) release in the immune system, but are also involved in regulating the pain relieving effects on the peripheral nervous system, and play a large part in preventing unnecessary immune action upon the natural flora of the gut. The endocannabinoid responsible for activating the CB2 receptor, 2-arachidonoylglycerol (2-AG), also triggers a biological response from the CB1 receptors, but at a much lower rate than it does for the CB2 receptors (whereas the "bliss" molecule AEA only activates the CB1 receptors). 2-AG is involved in the management of appetite regulation, immune system functions, and pain responses. FAAH doesn't effect 2-AG like AEA, so it has its own unique breakdown enzyme, monoacylglycerol lipase (MAGL).

While CB1 receptors and CB2 receptors are the most widely known and acknowledged cannabinoid receptors, several other receptors, ranging from other G protein-coupled receptors (GPCRs) to transient receptor potential (TRP) channels, and peroxisome proliferator activated receptors (PPAR's), have been reported to interact with cannabinoids. Research into all the mechanisms involved in the endocannabinoid system as well as their effects is ongoing. As with most continuing studies, at some point there will be even more information to add.

That's where I'm going to cut myself off this week. I'm still working on trying to condense my Alphabet Soup of Phytocannabinoids into a single article, but it's looking like that's going to be one of those pipe dreams. So there will probably be at least two more cannabinoid articles coming your way over the next couple of weeks. Until next time, keep warm and, as always, keep it Okie Tokie my friends.

-P.A. Murphy

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