The Endocannabinoid System (ECS)

The Endocannabinoid System (ECS)

Chapter 1

The relatively recent discovery of the endocannabinoid system1 (ECS) has been a driving force for scientific research into the potential therapeutic effects of CBD on the body. Before the  ECS was discovered in the 90s, not much was known about how the cannabis plant and all its derivatives affect the human body. The ESC is a network of cannabinoid receptors both in the brain and in peripheral tissues. There is still much that unknown about the ECS, however, evidence suggests that having a strong understanding of the endocannabinoid system may lead to preventing, managing, or even treating certain chronic conditions2

The endocannabinoid system is made of endocannabinoids and cannabinoid receptors. 

Endocannabinoids are endogenous ligands that activate the cannabinoid receptors. A ligand is a protein that binds (attached) to a receptor. This is a specific fit - a good analogy will be a key (ligand) and a lock (receptor). Endogenous ligands are ligands that are produced in the body. 

So how does all this relate back to cannabis? Well, that’s where Phytocannabinoids come in. Phytocannabinoids are the major active compounds found in the cannabis plant, including the famous THC and CBD and also less known cannabinoids including CBN, CBDa, CBG, and CBC. “Phyto-” denotes coming from a plant, as these are cannabinoids extracted from the cannabis plant, but they have a molecular similarity to the endocannabinoids that are naturally produced in our body. It is this molecular similarity that allows the phytocannabinoids to affect the endocannabinoid system in our body.


What Does the Endocannabinoid System Do, Exactly?

The ECS is a signaling system, and as such helps the body remain balanced and to operate  effectively3

The ECS is involved in the healthy function of major systems such as the brain, liver, reproductive system, cardiovascular system, and more, and has been linked to both physical and mental conditions4 5 :

  • Learning, memory & cognition 
  • Anxiety and depression 
  • Sleep
  • Appetite
  • Addiction
  • Liver function
  • Fertility 
  • Metabolism 
  • Energy balance

Among others. 


How Does CBD Affect the Endocannabinoid System? 

CBD stands for Cannabidiol and it is one of the major active cannabinoids in the cannabis plant along with the more well-known compound, THC. As you now understand, plant cannabinoids can trigger the same receptors as the body’s own natural endocannabinoids. 

The body has two major cannabinoid receptors, CB1 and CB2 and are activated by THC, which causes the famous ‘high’. CBD has negligible affinity to the CB1 and CB2, however “recent studies have suggested that it is an allosteric modulator and an indirect antagonist of CBRs with the ability to potentiate the effect of THC”6 7

The two main endocannabinoids, made naturally by the body, are anandamide and 2-arachidonoylglycerol (2-AG). Anandamide is often called the “feel good” molecule or the “bliss molecule” and it plays a role in appetite regulation and the generation of pleasure and motivation. Anandamide mainly targets the CB1 receptors, mainly found in the brain and nervous system, while 2-AG activates both CB1 and CB2. THC, similar to Anandamide, has a very high binding affinity for CB1 receptors, higher than with the CB2 receptor.  CBD, on the other hand, does not interact with the CB1 and CB2 receptors directly, but has benefit of limiting the effects of THC on the CB1 receptor, thus reducing any unwanted effects that may result from THC such as paranoia, anxiety, impaired movement, impaired memory, altered sense of time or even, when taken in high doses, delusions, hallucinations or psychosis8.

Although CBD does not directly activate the cannabinoid receptors, it is an integral and important part of the ECS. By moderately inhibits the degradation of the endocannabinoid anandamide9 and thus positively affect both physical and mental well being.  Through its relationship with the ECS, “CBD has demonstrated anxiolytic, antidepressant, neuroprotective antiinflammatory, and immunomodulatory benefits10.

In conclusion, the ECS is an important biochemical signaling system that helps shape our understanding of how cannabinoids affect the human body and our health. Although CBD does not directly activate the cannabinoid receptors, it is still engaging with the ECS receptors and endocannabinoids and it is that interaction that is behind CBD’s potential health benefits11


  1.  Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346:561–564.
  2. The Endocannabinoid System and Chronic Disease A. Yoder, in Physical Activity and the Aging Brain, 2017
  3. Zou S, Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018;19(3):833. Published 2018 Mar 13. doi:10.3390/ijms19030833
  4. As above
  5. Lu HC, Mackie K. An Introduction to the Endogenous Cannabinoid System. Biol Psychiatry. 2016;79(7):516–525. doi:10.1016/j.biopsych.2015.07.028
  6. Zou S, Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018;19(3):833. Published 2018 Mar 13. doi:10.3390/ijms19030833
  7. Laprairie R.B., Bagher A.M., Kelly M.E., Denovan-Wright E.M. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br. J. Pharmacol. 2015;172:4790–4805. doi: 10.1111/bph.13250
  8. Russo EB, Guy GW. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses. 2006;66:234–246
  9. Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2(3):e94. Published 2012 Mar 20. doi:10.1038/tp.2012.15
  10. Joseph Maroon, Jeff Bost. Review of the neurological benefits of phytocannabinoids. 26-Apr-2018;9:91
  11. Maroon J, Bost J. Review of the neurological benefits of phytocannabinoids. Surg Neurol Int. 2018;9:91. Published 2018 Apr 26. doi:10.4103/sni.sni_45_18 

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