Caution: understanding the Endocannabinoid System might change your life!

understand endocannabinoid system - nature going smart


  • 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:

1) What is the Endocannabinoid System?

2) What are Cannabinoid Receptors?

3) What’s an endocannabinoid?

4) Synthetic Cannabinoids

5) Support & Copyright 

The endocannabinoid system, named after the plant that led to its discovery, is the most important physiologic system involved in establishing and maintaining human health.
Plant, DNA and life green science

“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

Endocanabinoid system brain - Nature Going Smart

What is the Endocannabinoid System?

The endogenous cannabinoid system, named after the plant that led to its discovery, is perhaps the most important physiologic system involved in establishing and maintaining human health.

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.

Find out better how cannabinoids are effective anti-tumoral agents  and  what therapy could assist you to fight cancer.

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.

Check out why cannabinoids are the best option for chronic pain, neuropathic pain or inflammatory pain.

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.

endocannabinoid system activation signalling

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 (CBNand 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)


Synthetic Cannabinoids

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)

If you are interested to know which Countries approve medical use of these cannabinoids, and what phathologies have been authorized prescription, I suggest you to check here or watch this video.

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.

Spread consciousness and smile more!


Nature Going Smart - SupportDid you like this article on the endocannabinoid system?

This original content has been offered for free without advertisements thanks to our readers’ contributions. You, too, can support us in many ways. Check out how here! Thank you  

Copyright, Nature Going Smart. May not be re-printed without permission.

Viola Brugnatelli

Viola Brugnatelli is a Neuroscientist specialised in Cannabinoid circuitry & GPCRs signalling. Her academy and research training let her gain extensive experience on medical cannabis and terpenes both from preclinical as well as clinical perspective. In her vision, collective human knowledge behold the power for overall improvement of life, thus, it should be accessible and shareable. Viola is Founder of the science online magazine Nature Going Smart, and works as a consultant for companies & individual patients, as a speaker at seminars and workshops and as a lecturer in a CME course on Medical Cannabis in Italy, at the University of Padua.

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20 Responses

  1. Bernadette Bermea says:

    Hello, my name is Bernadett Bermea… I have been educating myself on the benefits of cannabis for a good while now. I have done my share of investigation. But I do need some advice and couseling from an expert. I have a project in mind… but i do need help…Thank you for your time and hope to hear from you soon!

    • Viola Brugnatelli says:

      Hello Bernadette,

      Thank you for writing.
      We are happy to have you here continuing your self-education! if you have any queries, we are happy to help, you can write us at our

      All best!

  2. mark shanklin says:

    I was hoping for more information, how different cannabinoids work on different receptors. Does THC and CBD work on the same receptors ?
    Something I’ve wondered is; organ transplant patients experience memories and/or changes in tastes and other things ( never driven a car with a clutch but now there leg “remembers”), and since receptors are all over the body , is the Endocannabinoid system somehow the explanation for this? That the brain is not the only storage for memories ? Does this make sense?

    • Viola Brugnatelli says:

      Hello Mark, thank you for your feedback.
      THC is a CB1 and CB2 receptor partial agonist, whilst CBD seem to be an inverse agonist of CB2 receptors, and possibly an antagonist at CB1. Both compounds probably work on many more receptor targets, such as GPR55 and GPR18, but also PPARs. Ongoing studies on pharmacology are trying to establish this. If you want to know more on the pharmacology of these compounds, I recommend you read this paper from the very talented Dr Roger Pertwee

      As for your second question, “movement memory” or “procedural, implicit memory” (“knowing how”) is the unconscious memory of skills and how to do things, particularly the use of objects or movements of the body. EC are widespread and also work in this brain area. I personally am unaware of specific publications on the topic of changes post-transplantation. But I do recall a very old study made on worms, (1960 from James V. McConnell) where trained worms fed to untrained worms (naive), could transfer many of their learned skills. Such study has been criticised a lot at the time, probably the interpretation of the author (that was due to RNA) was somehow off, but the experiment was legit, and I personally believe that knowledge & memory is beyond embedding in the brain, but rather encoded in electromagnetism. If so, then surely endocannabinoids play a part, being very important in neural transmission (and final electric stimuli). Hopefully my answer did not confuse you further, many questions remain open…and, well, science is still so behind nature!

  3. Anthony says:

    I am a nurse. I know that cannabis is safer than alcohol.
    Thank you for sharing the helpful overview Dr. Sulak. I want to learn more about the science, but more urgently, I want to end the war on drugs which I call a war on people. Any thoughts? My book is a free PDF Download. Thank you

    • Viola Brugnatelli says:

      Hey Anthony,

      Your blog is full of the right courage- thank you for sharing it with us.

  4. Anonymous says:

    I used cannabis to kill my cancer 🙂

  5. Eleene Hoskins says:

    This kind of good information needs to get out to the general public, elected officials and doctors so they can understand, that this is a good product with no side effects and does a lot of good in a very period of time. Raw Hemp Oil 300MG (CBDa&CBD) saved me from a life of terrible pain and suffering from Fibro, Nephropathy. Big Pharma several of their meds side effects all most killed me on 3 different occasions in the past 10 yrs. I have my life back now.

  6. brenda stacy says:

    thank you for this information i plan to print and give copy to my drs to help them understand. My family dr is wanting to learn more so i am sure this is a good start for her.

  7. Transhuman says:

    Very interesting article.

    I’m into supporting Longevity related causes, but I haven’t really looked into what role this could play in that as of yet.

    I’ll be taking the time to look into your site a lot more for sure.

    If others here are interested in health and longevity, I’d suggest taking a look at too.

  8. Alex says:

    Can I take CBD for a psychic disorder instead of taking pharmaceutical antipsychotics?

  9. Alex says:

    Can I take CBD for a psychotic disorder instead of taking pharmaceutical antipsychotics?

    • Hello Alex,

      CBD is increasingly considered as an anti-psychotic agent. Several human and animal studies have shown that CBD reduces anxiety probably via serotonin receptors.
      Unfortunately we cannot advice you on what’s best to do for your case, but you could talk about it with your current physician before opting for traditional pharmacology.

  10. Dane Silva says:

    Im happy to read that someone else is speculating about G-Protein Coupled Receptors, as well as CB1 and CB2.

  11. Naimah says:

    I love your work! I use CBDs for many reasons and I can not get enough of learning about our endocannabinoid system, and want to eventually teach others of what I understand. May I share your articles as a reference on my page? And may I please quote your work ma’am?

  12. Lion Goodman says:

    We offer a free ebook, – filled with good information about CBD, CBD products, and the science behind it. In September, our major book is coming out from No. Atlantic Books: “CBD: A Patient’s Guide to Medicinal Cannabis – Healing Without the High.” It contains more than 400 scientific and medical citations. Viola – I will be happy to send you an advanced copy for your review. For the public, register to be notified when it’s available at

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