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Category: About CBD, Cannabinoids, CBD Benefits, Health

What is the endocannabinoid system and what's its role?

Endocannabinoid System

Written by our editorial team

Last updated 6/03/2021

The first known records of medicinal cannabis use date back to 3,000 BC, when the Chinese used the cannabis plant to relieve cramps and pain. Despite its medicinal benefits, which were also reported in 1,000 BC India, it took the plant nearly five thousand years to finally make its way from Asia to Europe and America in the 19th century.[18]

And while the primary driver of cannabis adoption in the West might have been its psychoactive effects, the medicinal benefits also played a major role in its immediate widespread popularity. This was until 1937, when the Marijuana Tax Act banned the possession and transfer of marijuana across the USA based on concerns about the dangers related to its abuse.[1]

But studies on the medicinal effects of cannabis continued and, eventually, a few major discoveries were made. The identification of the first cannabinoid receptor in the late 1980s[15] and the identification of the first endocannabinoid in the early 1990s[8] lead to a major scientific breakthrough with the discovery of the so-called endocannabinoid system.

This introductory blog post sheds light on the endocannabinoid system, its components, its importance for the human body and its interactions with the naturally occurring cannabinoids found in Cannabis sativa and Cannabis indica.


[3-minute read]

The endocannabinoid system is a system composed of:

  • Cannabinoid receptors detecting molecules outside the cell and activating cellular responses,
  • Endocannabinoids that activate cannabinoids receptors and carry signals between nervous cells,
  • Metabolic enzymes that aid in the synthesis and degradation of endocannabinoids,
  • And all neurons, pathways and other cells where cannabinoids receptors, endocannabinoids and metabolic enzymes co-occur.

The endocannabinoid system aids in homeostasis, which is an ongoing process in which the body maintains the ideal balance between all body systems.

  • It ensures the normal functioning of the nervous system, cardiovascular system, gastrointestinal system, reproductive system, immune system and metabolic processes.

Cannabinoids found in Cannabis sativa and Cannabis Indica can activate cannabinoid receptors for a variety of beneficial effects:

  • Managing stress and anxiety,
  • Relieving chronic pain,
  • Decreasing appetite to aid in weight loss.

1. Building blocks of the endocannabinoid system

The endocannabinoid system is a biological system of receptors and neurotransmitters, which facilitates cell signalling. It is not found only in humans, but in all vertebrates.[17] There are many questions about the endocannabinoid system that remain unanswered to this day, but we do that it is made up of three key components (see Figure 1 below):

#1 Cannabinoid receptors, which are receptors found in the central and peripheral nervous systems, immune system and gastrointestinal system. They are essentially proteins that function as receptors embedded on the membranes of cells. Their function is to detect molecules outside the cell and activate certain cellular responses. So far, we have identified two types of cannabinoid receptors, but studies have proposed that there might be other, yet unidentified cannabinoid receptors.[11]

The two kinds of receptors we know are CB1 and CB2. CB1 is widely expressed in the brain and in the peripheral nervous system.[3] CB2 can also be found throughout the nervous system but is more prevalent in the gastrointestinal system and the immune system, where it can be found on immune cells such as B-cells and T-cells.[6]

#2 Endogenous cannabinoids, or endocannabinoids for short, are compounds that activate cannabinoid receptors and carry signals between nerve cells. What is interesting about endocannabinoids is that they are similar to the cannabinoids found in the cannabis plant, but they are produced in different peripheral tissues of the body, for instance in the walls of vessels[9] or in bones[10].

The first endocannabinoid was identified by Raphael Mechoulam, W. A. Devane and Lumír Hanuš in 1992.[8] Since then, several other endocannabinoids have been identified, but the two that we have been studied most extensively are AEA and 2-AG.

#3 Metabolic enzymes are special proteins that act as catalysts in the synthesis and degradation of endocannabinoids. One metabolic enzyme involved in the endocannabinoid system is FAAH, which aids in the synthesis of fatty acid amides, such as endocannabinoids AEA and 2-AG.

Figure 1: Simplified scheme of the endocannabinoid system

Cannabinoid receptors

But the endocannabinoid system also comprises other components aside from cannabinoid receptors, metabolic enzymes and endocannabinoids. To be completely accurate, the entire endocannabinoid system is composed of these three components in addition to the neurons, neural pathways and all other cells in the body where these three components co-occur.

2. Endocannabinoid system – the orchestrator of the human body

Our bodies have to maintain a constant balance between all body systems in order to function properly. They have to react to internal and external changes by adjusting the body levels of acid, blood pressure, blood sugar, electrolytes, energy, hormones, oxygen, proteins and temperature accordingly. This striving of our bodies to maintain an ideal balance is known as homeostasis.[14]

As we have already learned, cannabinoid receptors CB1 and CB2 are found throughout the human body (see Figure 2). And this is for a good reason. The endocannabinoid system aids in homeostasis to ensure the normal functioning of the nervous system, cardiovascular system[4], gastrointestinal system, reproductive system[12], immune system and metabolic processes[7]. Much like an orchestra needs a maestro, our bodies need the endocannabinoid system. Without it, the show is over.

Figure 2: Locations of cannabinoid receptors CB1 and CB2

Locations of Cannabinoid Receptors

3. Do cannabinoids found in plants interact with the endocannabinoid system?

Let us take a step back. We said that endocannabinoids trigger cannabinoid receptors, and we also said that endocannabinoids are similar to cannabinoids found in the cannabis plant. This begs a valid question. Can cannabinoids in cannabis also trigger the cannabinoid receptors in our bodies? The answer is yes. And what is more, these cannabinoids provide a treatment option a variety of conditions and disorders:

1) Stress and anxiety

Are you feeling stressed or anxious? Then you are not alone. In fact, nearly three quarters of people in the developed world are stressed beyond the ability to cope.[13] And while there are pharmaceutical options available for treating such disorders, they are often accompanied by a long list of negative adverse effects.

According to the National Institute on Drug Abuse, CBD has been shown to treat different anxiety disorders, reducing both the behavioral signs of anxiety as well as the associated physiological symptoms, such as increased heart rate.[15] What is more, CBD has also been proven to successfully treat insomnia in nearly two thirds of study participants.[20]

2) Chronic pain

Aside from stress and anxiety management, CBD is also useful in patients suffering from conditions associated with chronic pain, such as arthritis or headaches, since animal studies have linked CBD to analgesic and anti-inflammatory properties. And while clinical studies have yet to confirm its effectiveness in humans, the Arthritis Foundation claims some individuals with arthritis have reported noticeable pain relief.[5]

3) Obesity and diabetes

Aside from CBD, another highly promising cannabinoid is THCV. An analogue of THC but without its psychoactive effects, THCV is especially interesting due to its appetite suppressing characteristics. In animal studies, THC has been shown to reduce appetite, increase satiety and up-regulate metabolism. This makes THCV a promising natural substance for weight-loss management and diabetes treatment.[2]

These are just two of the cannabinoids that exhibit beneficial synergies with the endocannabinoid system. Since there are numerous other plant-found cannabinoids out there, we are just scratching the surface with their medicinal use cases.

If you are interested in other beneficial effects of cannabinoids on the human body, stay tuned for our upcoming blog posts. In our next post, we will dive deeper into the effects of THCV, which presents a valid weight-loss method without any observed negative adverse effects.

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

Bibliography and sources

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  3. Abood, M. et al. (22 August 2018). “CB1 Receptor”. IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 9 November 2018.
  4. Alfulaij, N. et al. Cannabinoids, the Heart of the Matter”. Journal of the American Heart Association 2018 Jul 13;7(14):e009099. [doi:10.1161/JAHA.118.009099]
  5. Arthritis Foundation. “CBD for Arthritis Pain: What You Should Know”. Accessed on 12 February 2021. [URL:]
  6. Basu, Sreemanti et al. “Cannabinoid receptor 2 is critical for the homing and retention of marginal zone B lineage cells and for efficient T-independent immune responses.” Journal of immunology (Baltimore, Md.: 1950) vol. 187,11 (2011): 5720-32. [doi:10.4049/jimmunol.1102195]
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  8. Devane, W. et al. (18 December 1992). “Isolation and structure of a brain constituent that binds to the cannabinoid receptor”. Science. 258 (5090): 1946–1949. [doi:10.1126/science.1470919]
  9. Hillard, Cecilia J. “Endocannabinoids and vascular function”. Journal of Pharmacology and Experimental Therapeutics 294(1):27-32. Accessed on 8 February 2021. [URL:]
  10. Idris AI, Ralston SH. Cannabinoids and bone: friend or foe? Calcif Tissue Int. 2010 Oct;87(4):285-97. [doi: 10.1007/s00223-010-9378-8]
  11. Járai, Z et al. (November 1999). “Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors”. Proceedings of the National Academy of Sciences of the United States of America. 96(24): 14136–41. [doi:10.1073/pnas.96.24.14136]
  12. Maroon, J.; Bost, J. “Review of the neurological benefits of phytocannabinoids.” Surgical neurology international vol. 9 91. 26 Apr. 2018. [doi:10.4103/sni.sni_45_18]
  13. Mental Health Foundation (May 2018). Stress: Are we coping? London: Mental Health Foundation. Accessed 12 Febuary 2021. [URL:]
  14. National Cancer Institute. Homeostasis. Accessed 8 February 2021. [URL:]
  15. National Institute of Drug Abuse. “Marijuana Research Report How does marijuana produce its effects?” Accessed 9 January 2021. [URL:]
  16. National Institute on Drug Abuse (June 2015). The Biology and Potential Therapeutic Effects of Cannabidiol. Accessed on 12 February 2021. [URL:]
  17. Oltrabella, Francesca et al. “Role of the endocannabinoid system in vertebrates: Emphasis on the zebrafish model.” Development, growth & differentiation vol. 59,4 (2017): 194-210. [doi:10.1111/dgd.12351]
  18. Pacher, P. et al. “The endocannabinoid system as an emerging target of pharmacotherapy.” Pharmacological reviews vol. 58,3 (2006): 389-462. [doi:10.1124/pr.58.3.2]
  19. Pertwee, Roger G. “Cannabinoid pharmacology: the first 66 years.” British journal of pharmacology vol. 147 Suppl 1, Suppl 1 (2006): S163-71. [doi:10.1038/sj.bjp.0706406]
  20. Shannon, Scott et al. “Cannabidiol in Anxiety and Sleep: A Large Case Series.” The Permanente journal vol. 23 (2019): 18-041. [doi:10.7812/TPP/18-041]
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