The Endogenous Cannabinoid System

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The natural cannabinoids of cannabis, in particular THC, act on the human organism in a way that is similar to the endocannabinoids, endogenous substances that carry out a multitude of functions in the human body. These endocannabinoids (from the Greek endo, which means “inner”), or endogenous cannabinoids, are found not only in human beings but also another vertebrates (mammals and birds) and in a great number of primitive animals. THC, like the endocannabinoids, connects to specific sites present on the surface of numerous cells, which then sets in motion its effects. These sites are called cannabinoid receptors. Together, the endocannabinoids, the enzymes, and the cannabinoid receptors form the endogenous cannabinoid systems, which plays an important role in the regulation of appetite and in the perception of sensory information or information relating to pain, as well as movement coordination.

Other natural cannabinoids present various action mechanisms.

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Cannabinoid Receptors

It was demonstrated for the first time in 1987 that most of the effects attributed to the cannabinoids get conducted through their connection to specific receptors. These cannabinoid receptors are mainly located on the membranes of brain cells and in the spinal marrow. They are also present in cells of the heart, the intestines, the lungs, the skin, the urinary tract, the uterus, the testicles, the internal glands, the spleen, and the white blood cells. Depending on where these receptors are located, their activation will induce very different effects–for example, an inhibition of nociceptive pathways, an inhibition of inflammatory processes, a modification in the perception of time, or a feeling of euphoria or other effects in the mind.


The first endocannabinoid was discovered in 1992. It was named anandamide, from the Sanskrit ananada, meaning “supreme happiness,” and amide, designating its chemical structure. Later, other endocannabinoids were discovered, but their names are less poetic and sound more scientific, such as 2-arachidonoylglycerol and noladine ether. Today, we count around two hundred varieties of endogenous substances close to the endocannabinoids, the effects of which have mostly not yet been studied in detail. The endocannabinoids are grouped with other substances that play the role of natural messengers. They transmit information concerning the state of the organism to the brain and other organs, thus provoking reactions at a cellular level. They belong to a group of the main inhibitory neurotransmitters and play a significant role in, for example, acting as a brake on the excessive discharge of glutamate in the brain when it is subjected to a lack of oxygen supply. This is why one of the main functions attributed to the endocannabinoids is that of protecting nerve cells. Other neurotransmitters that act under the influence of the endocannabinoids include GABA, glycine, noradrenaline, serotonin, dopamine, and acetylcholine, as well as the neuropeptides (enkephalin and endorphin).

Often, the medical properties of cannabis can be explained by the interactive effects of these messengers. The inhibition of the release of serotonin relieves nausea and vomiting, and the influence exercised by GABA and acetylcholine is beneficial in countering neuromuscular disorders such as spasms or cramps.

black and white illustration of the chemical makeup of two endocannabinoids

The Evolution of the Endocannabinoid System in Case of Illness

With certain physical disorders, and to compensate for them, the average production of endocannabinoids and the number of receptors become modified. Thus, in the case of pain, the concentration of anandamide increases in certain cerebral regions that are responsible for pain management so as to relieve the pain. In the case of undernourishment, this production increases to more effectively stimulate appetite. Research conducted with animals has shown that the quantity of anandamide in the intestines multiplied if the animals were deprived of nourishment for a certain time and that this level came back to normal once adequate levels of nourishment returned. In addition, it became clear that the production of endocannabinoids in the organism intensified during muscle cramps, evidently to relieve these painful contractions. In the case of pain caused by neuritis or chronic inflammation of the intestines, the number of cannabinoid receptors also increases considerably.

The cannabinoid system adapts, therefore, to situations linked to the appearance of a pathological condition. Such a multiplicity in the number of cannabinoid receptors in certain parts of the body and in the course of certain illnesses can result in an improved effectiveness of the exogenous natural cannabinoids. This is why the natural functions of the endocannabinoid system have been studied so closely for several years now in the hope of finding new medications based on an improved understanding of this complex system.

Other Effects

Certain cannabinoid effects do not result in the activation of the cannabinoid receptors but rather are the product of other mechanisms. For example, cannabinoids, like vitamins C and E, are powerful detectors of free radicals. Free radicals are highly reactive molecules capable of causing cellular lesions.

Similarly, certain products of the biochemical deterioration of THC have very interesting medical properties. Whereas the activities set in motion in the human organism by 11-hydroxy-THC as well as THC are comparable, that of 11-nor-9-carboxy-THC (THC-COOH) is different. THC-COOH has an anti-inflammatory and analgesic action that is comparable to that of acetylsalicylic acid (aspirin): both inhibit the enzyme cyclooxygenase. THC-COOH, however, acts more specifically and does not cause the side effects of aspirin, such as gastric or kidney disorders. In a general way, the products of biochemical deterioration of the cannabinoids contribute strongly to their overall medical properties.

black and white illustration of two versions of the chemical THC

Certain effects of cannabinoid compounds are caused by the effects of cannabinoids other than THC. CBD (cannabidiol), for example–the cannabinoid present in cannabis in the next greatest quantity after THC–presents antiemetic, neuroprotective, anxiolytic, and anti-inflammatory properties. Its mechanism of complex functioning presents an inhibiting effect (antagonic) of the type 1 cannabinoid receptor, a stimulating effect of the type 1 vanilloid receptor, an inhibition of the deterioration of the anandamide endocannabinoid, and an activation of cellular nucleus receptor PPAR-gamma.

Note to reader: This excerpt is intended as an informational guide. The remedies, approaches, and techniques described herein are meant to supplement, and not to be a substitute for, professional medication care or treatment. They should not be used to treat a serious ailment without prior consultation with a qualified health care professional.

white book cover with a cannabis leaf

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Excerpted with permission from Cannabis Healing A Guide to the Therapeutic use of CBD, THC, and Other Cannabinoids by Franjo Grotenhermen, M.D., published by Park Street Press, 2020.