Endocannabinoid System - Endourage

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Endocannabinoid System

Your endocannabinoid system (ECS) is a group of specialized fatty acid-based lipid signaling chemicals, their receptors, and the metabolic enzymes that produce and break them down. It was named after the plant that led to its discovery, cannabis, and although detected in the early 1980s, its existence wasn’t confirmed until 1992 by a group of Israeli researchers. It was later discovered that all vertebrates have an endocannabinoid system, and it’s believed to have first appeared in animals 525 million years ago during the Cambrian explosion when life first began to drastically diversify. Nearly every creature on the planet, excluding insects, arachnids, molluscs, jellyfish, sponges, worms, corals, flatworms and crustaceans, has an endocannabinoid system.

Purpose of your ECS

Your ECS’ main purpose is to regulate vital functions in the body, including sleep, pain sensitivity, mood regulation, inflammation, appetite, body heat, muscle tone and movement, extinction of traumatic memory, protection of nerves and brain tissue, bone growth, tumor regulation, mediation of communication between cells, eye pressure, seizure activity and stress regulation. It does this by naturally creating and binding special chemicals called endocannabinoids, such as anandamide (AEA) and 2-arachidonoylglycerol (2AG), to cannabinoid receptors found throughout the body. These receptors consist of 472 amino acids strung together in a chain that squiggle back and forth across cell membranes in an alpha helix. Rats’ CB receptors are made up of 473 amino acids, and are 99% identical to humans, which is why preclinical rodent trials have much more value in the field of cannabinoid testing. CB1 receptors are predominantly found on brain and glial cells in the prefrontal cortex, cerebral cortex, hippocampus, amygdala, basal ganglia and cerebellum, as well as throughout the central nervous system in the dorsal primary afferent spinal cord regions and spinal interneurons, and mature slowly as one ages, reaching maximum levels during adolescence. CB2 receptors are found mostly in the body’s immune system, gastrointestinal system, nervous system, tonsils, spleen and on white blood cells. Though these are the main locations, they can also be found in smaller amounts throughout the body, including the bones, reproductive organs, heart, liver, adipose tissue, and even certain regions of the brain as well, including the prefrontal cortex, hippocampus and hypothalamus, but are not involved in the psychotropic effects of cannabinoid-based substances. CB1 and CB2 receptors share 40 – 50% amino acid sequence homology, and are themselves a distinct class within the G protein-coupled receptor family.

An example of a natural influx of endocannabinoids in your body is the “runner’s high,” which is the result of an increase of anandamide after a vigorous workout, and has been compared to a mild cannabis high. Anandamide is also produced en masse when oxytocin levels in the body rise, such as when someone is experiencing love. Additionally, it was discovered in 1996 that even chocolate contains concentrated anandamide, which can help explain why so many enjoy it.

Phytocannabinoids

Phytocannabinoids are a group of chemicals produced by the cannabis plant that, sheerly through coincidence, are capable of binding to the same cannabinoid receptors found in our bodies, hence their name. While tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two most common phytocannabinoids, cannabis has at least 113 different kinds, all with their own effects and properties. Terpenes and terpenoids, a separate category of chemicals, are aromatic oils produced by flowering plants and are primarily responsible for distinct flavors and smells, but can also have their own minor effects. Terpenes themselves are not unique to cannabis and can be found in numerous other plants, such as hops, conifers, pine trees, oranges, pepper, lemongrass, etc. This is why marijuana strains can be so different from one another. The effects each strain produces, such as sleepiness from one and the munchies from another, are essentially a sum of these phytocannabinoids and terpenes.

When cannabis is consumed, the phytocannabinoids are transported through the bloodstream to the liver. Here, the cytochrome P450 system and its metabolic enzymes CYP1A2, CYP2C9, CYP2C19 and CYP3A4 break the phytocannabinoids down into further metabolites; THC, for example, eventually becomes 11-hydroxy-THC (11-OH-THC), which is further metabolized into 11-nor-9-carboxy-THC (THC-COOH). It should be noted that consumption of phytocannabinoids like THC and CBD directly inhibits the P450 system, so taking these alongside other drugs that rely on the same system, such as benzodiazepines, may have adverse effects. The bioavailability of phytocannabinoids such as THC have a variance between 10 – 35% when inhaled, a very high number, meaning two users can take an equal dose, and one of them could possibly experience a 3 times higher THC concentration. As a person consumes more cannabis, their bioavailability increases, allowing up to 50 – 70% more THC to enter circulation and be properly processed. The bioavailability of phytocannabinoids when ingested is between 4 – 12%, as something called the first-pass effect heavily diminishes the THC that is metabolized. The stomach absorbs more than 90% of the ingested THC and passes it on, but most of it is eliminated by the liver before it gets into circulation. This variance means that, given an equal dose, two people ingesting cannabis can experience the peak concentrations up to 6 hours apart.

Once the phytocannabinoids have been broken down into metabolites, they bind to the main endocannabinoid receptors CB1 and CB2, found throughout the body. Additionally, some phytocannabinoids like CBD can bind to numerous other types of receptors, such as the A2A, VR1, GPR55 and 5-HT1a receptors. A2A is the adenosine receptor associated with anti-anxiety, the regulation of blood flow and blood oxygen levels, and down-regulates the release of neurotransmitters like dopamine and glutamate. VR1 is the vanilloid receptor associated with pain perception, inflammation and body temperature, and may be a main reason CBD acts as a neuropathic pain treatment. GPR55 is the receptor associated with cancer, and when it is active, cancer proliferation is promoted. CBD appears to inhibit this receptor. 5-HT1a is the serotonin receptor commonly bound to by drugs like Lexapro, Prozac and Wellbutrin, influencing addiction, appetite, sleep, pain, nausea, vomiting, anxiety and depression. 

Different phytocannabinoids can have different effects depending on which receptors they bind to. For example, THC strongly binds to CB1 receptors found in the brain, which is why you receive a euphoric high. CBD, on the other hand, doesn’t bind strongly to CB1 receptors at all, hence its non-psychotropic properties. One of the few places CB receptors are not found is the brain stem, which is why it is realistically impossible to die from an overdose on cannabis.

Conclusion

If for whatever reason, be it a genetic deficiency or some sort of medical issue, your ECS is out of balance and is not producing adequate amounts of natural endocannabinoids, such as anandamide (AEA), consuming marijuana allows its phytocannabinoids to fill in the gaps. Since they affect the ECS in a very similar way to endocannabinoids, and since the ECS is responsible for so many vital functions in the body, phytocannabinoids are capable of helping a wide array of symptoms. This is the entire basis behind cannabis as a medicine.

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