Caution: understanding the Endocannabinoid System might change your life!
- The endocannabinoid system is the most important physiologic system involved in establishing and maintaining human health
- Sea squirts, tiny nematodes, and all vertebrate species share the endocannabinoid system as an essential part of life and adaptation to environmental changes
- Currently, there are two recognised cannabinoid receptors: CB1, predominantly present in the nervous system, connective tissues, gonads, glands, and organs; and CB2, predominantly found in the immune system and its associated structures
- Endocannabinoids are the substances our bodies naturally make to stimulate these receptors
- Phytocannabinoids are plant substances that stimulate cannabinoid receptors
Contents of this article:
“As a physician, I am naturally wary of any medicine that purports to cure‐all.
Panaceas, snake‐oil remedies, and expensive fads often come and go, with big claims but little scientific or clinical evidence to support their efficacy.
As I explore the therapeutic potential of cannabis, however, I find no lack of evidence.
In fact, I find an explosion of scientific research on the therapeutic potential of cannabis, more evidence than one can find on some
of the most widely used therapies of conventional medicine. “
Dustin Sulak, DO
Maine Integrative Healthcare
What is the Endocannabinoid System?
Endocannabinoids and their receptors are found throughout the body: in the brain, organs, connective tissues, glands, and immune cells.
In each tissue, the cannabinoid system performs different tasks, but the goal is always the same: homeostasis, the maintenance of a stable internal environment despite fluctuations in the external environment.
Cannabinoids promote homeostasis at every level of biological life, from the sub‐cellular, to the organism, and perhaps to the community and beyond.
Hereʹs one example: autophagy, a process in which a cell sequesters part of its contents to be self‐digested and recycled, is mediated by the cannabinoid system.
While this process keeps normal cells alive, allowing them to maintain a balance between the synthesis, degradation, and subsequent recycling of cellular products, it has a deadly effect on malignant tumor cells, causing them to consume themselves in a programmed cellular suicide.
The death of cancer cells, of course, promotes homeostasis and survival at the level of the entire organism.
Endocannabinoids are also neuromodulators, allowing communication and coordination between different cell types.
At the site of an injury, for example, cannabinoids can be found
- decreasing the release of activators and sensitizers from the injured tissue
- stabilizing the nerve cell to prevent excessive firing
- calming nearby immune cells to prevent release of pro‐inflammatory substances
Three different mechanisms of action on three different cell types for a single purpose: minimize the pain and damage caused by the injury.
What are Cannabinoid Receptors?
Sea squirts, tiny nematodes, and all vertebrate species share the endocannabinoid system as an essential part of life and adaptation to environmental changes.
By comparing the genetics of cannabinoid receptors in different species, scientists estimate that the endocannabinoid system evolved in primitive animals over 600 million years ago.
While it may seem we know a lot about cannabinoids, the estimated twenty thousand scientific articles have just begun to shed light on the subject.
Large gaps likely exist in our current understanding, and the complexity of interactions between various cannabinoids, cell types, systems and individual organisms can still offer novel ways to look at physiology and health.
The following brief overview summarizes what we do know, ( without getting over specific with terminology and mechanisms otherwise pedantic for general public)
Cannabinoid receptors are present throughout the body, embedded in cell membranes, and are believed to be more numerous than any other receptor system.
When cannabinoid receptors are stimulated, a variety of physiologic processes ensue.
Currently, there are two recognised cannabinoid receptors: CB1, predominantly present in the nervous system, (is the most abundant G-protein coupled receptor of the CNS) connective tissues, gonads, glands, and organs; and CB2, predominantly found in the immune system and its associated structures.
Many tissues contain both CB1 and CB2 receptors, each linked to a different action.
There are many researchers (like myself and many others investigating novel receptors), speculating on a larger number of cannabinoid receptors, such as GPR55, that are also sensitive to lipid cannabinoids.
What is important to understand for the purpose of this article, is that endocannabinoids are the substances our bodies naturally make to stimulate these receptors, and that these are fundamental for life.
Life is not possible in those of us who do not have cannabinoid receptors: in fact, depleting the gene encoding receptor sequence (in order to obtain a cannabinoid knockout KO -/-), prevents embryo development and survival to birth.
Learn more about cannabinoid receptors other than CB1 & CB2 in this excerpt:
What’s an endocannabinoid?
The two most well understood endocannabinoid molecules are called anandamide (from Sanskrit, bliss) and 2‐arachidonoylglycerol (2‐AG).
They are synthesized on‐demand from cell membrane arachidonic acid derivatives, have a local effect and short half‐life before being degraded by the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).
Chemically, endocannabinoids are eicosanoids (oxidised fatty acids) and for this reason during the International Cannabinoid Research Society symposium of 2014 at Baveno, Italy, it has been proposed to change the nomenclature of “endocannabinoids” to “eicosanoids” in order to prevent stigma for therapies that target the cannabinoid system, but clearly lack of the cannabis component. (This change has never taken place yet).
Phytocannabinoids are plant substances that stimulate cannabinoid receptors.
Most phytocannabinoids have been isolated from Cannabis sativa, but other medical herbs, such as Echinacea purpura, have been found to contain non‐psychoactive cannabinoids as well.
Delta‐9‐tetrahydrocannabinol, or THC, is the most psychoactive and certainly the most famous of these substances, but other cannabinoids such as cannabidiol (CBD) and cannabinol (CBN) and cannabinoid acids (THCA), are gaining the interest of researchers due to a variety of healing properties (that are further discussed here).
Interestingly, the Cannabis plant uses cannabinoids to promote its own health and prevent disease.
Cannabinoids have antioxidant properties that protect the leaves and flowering structures from ultraviolet radiation ‐ cannabinoids neutralize the harmful free radicals generated by UV rays, protecting the cells.
In humans, free radicals cause aging, cancer, and impaired healing, which can lead to a variety of pathologies, from neurodegenerative to immune disorders. Antioxidants found in plants have long been promoted as natural supplements to prevent free radical harm.
(Here you will find many antioxidant-rich recipes to include in your diet)
Cannabinoids have also been synthesised, and whilst some remain mainly in the research domain (Usually those with long codes-like letters and numbers), several synthetic analogs of THC or THC+CBD combination are both prescribed for oral or sublingual intake. (We have a guide on these kind of products)
CBD or Raw CBD (+CBDa) is available in many Countries as food supplement due lack of restrictive prescriptions on non-psychoactive compound. (However, we recommend you to check certification of providers (as we outlined in this article: “The importance of Cannabinoid Analysis”, and if you are unsure get in touch with our team for consulting)
In order to understand whether whole plant or single compound may be better for you, please read here.
This introduction to the Endocannabinoid System has been written thanks to the brilliant yearly review of recent scientific literature of “Emerging clinical applications of cannabis and cannabinoids” , by Paul Armentino, Deputy Diector of NORML (Check and support their work if you read from the States!) , they have a gift for concise and educational summary and I felt it was the best approach (compared to the peer-reviewed publication model I often adopt), in order to introduce the basics of the Endocannabinoid System.
All the information is indeed coming from an extensive work of review on the 15,899 articles on PubMed related to cannabinoids NORML does yearly, as well as a very interesting speech by Dr William Courtney during the ICRS 2014 annual symposium (check out his and his wife’s pioneering work with edible raw cannabis here) and my own understanding from previous years of studies and work on the topic.
If you want to delve in the topic, stay tuned for 2017 new articles either by signing in through the newsletter (I promise that you only receive a lovely once a month email, so no cluttering your inbox) or following us through the Facebook page or YouTube.
I am happy to read your comments and suggestions for new insights, so just leave them below.
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