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Our bodies have all kinds of systems to communicate between cells, to regulate cellular and tissue equilibrium, and to respond to stimuli both large and small. Among the many thousands of these systems, there are multiple pain systems and multiple inflammatory systems, etc. One is actually named after the active ingredients of the cannabis plant is called the “Endo’cannabinoid system, and it combines both pain relief and inflammation control. ‘Endo’ meaning internal or within, i.e. endogenous. And the more we learn about it, the more important is seems to become.

Turns out, all mammals have it, all vertebrates have it, nearly all animals have it, all except insects and some of the most primitive animals like sponges and starfish (1-4). Which basically means it is conserved across evolution, which in turn means it must be critically important. In fact, the ECS is critical for embryo development and post-natal development (4,5) and long-term survival.

The point is that the Endocannabinoid System is fundamental to all mammals, and is not just there to get us high. And Cannabis itself is just one of those plants that interacts with our body’s systems. It just so happens to be this particular system has many different and important effects. We are still learning why, and exactly what the ECS does and how it does it. It is anything but simple, but cannabinoids have so much potential it is well worth the effort.

Figure 2. The Endocannabinoid System. The cell membrane associated CB1 and CB2 receptors and their natural Ligands Anandamide and 2-AG ( chemicals that activate them ) and the Cannabis derived ligands, THC, CBD, and 133+ other cannabinoids.

There are two primary cell receptors that are the ignition switches to the Endocannabinoid System, CB1 and CB2 ( short for Cannabinoid Receptor 1 and Cannabinoid Receptor 2. ) They are both found in many of our cell’s membranes to a greater or lesser extent, with CB1 more associated with our brains and Central Nervous System (CNS) and while CB2 is also found in our brains and CNS, it is more associated with our immune and inflammatory systems scattered throughout our bodies. These receptors more specifically belong to a wide-ranging thousand-member family of cell receptors called “G-Protein Coupled Receptors” (GPCR for short) that do all sorts of things. They all are receptors stretching through the cell membrane connected to a ‘G-Protein’ inside the cell, that takes signals from outside the cell and then starts many different reactions inside the cell through changes in that ‘G-Protein’, which then has multiple and sometimes confusing downstream effects inside the cell (hence some of our confusion about the effects of THC and CBD).

We’ve known about Cannabis for thousands of years; we’ve known about the cannabinoids THC and CBD for over 100 years. We’ve only known about the receptors, CB1 and CB2, and their signaling molecules, Anandamide and 2-AG, only for the last 30 years.

CBD was first isolated, synthesized, and patented by a Dr. Roger Adams in the late 1930s. And although THC was known to him and actually synthesized by him in the lab, it was first truly isolated, and its structure determined by Israel’s Dr. Raphael Mechoulam in the 1960s. At first it was thought THC and CBD acted on already known receptors, but that proved to not be true and further research finally determined that it was in fact other unknown receptors that were the targets. It took 30 years to find them, from 1960 until the early 90’s. And then a few more years to find the chemicals that activated them, now known as Anandamide and 2-AG. (it didn’t make sense that our bodies would evolve a receptor that would only work with chemicals from cannabis.)

And we are still finding even more cannabinoid receptors, one now officially called CB3, with several more still being investigated. In total, they represent only a small fraction of a percent of the CB1/CB2 prevalence. And a key fact to keep in mind, even with CB3 and possibly CB4, 5, or even a CB6, most of the effects, 99+ % of all cannabinoid effects, are due to CB1 and CB2.

So, anyone telling you about any other magical cannabinoid effects is just blowing smoke. (this is called foreshadowing which we’ll cover later when I talk about the supposed magic of Terpenes, the entourage effect, and the true magic of maple syrup.)

In summary, the Endocannabinoid System is innate to humans, to mammals, and to all vertebrates. It consists of two endocannabinoid receptors called CB1 and CB2 and two endocannabinoid ligands called Anandamide (the bliss molecule) and 2- AG, which are mimicked by the two main cannabis molecules, THC and CBD which make up 95 % or more of the cannabinoids that occur naturally in the plant, with the other 131 cannabinoids combined making up less than 5%.

Individually or in combination, THC and CBD, affects our pain system and our immune/inflammatory systems. How it does this is exceptionally complex and mostly still a mystery which we’ll get into in a later chapter.

Next up will be how to tell what you are buying.


  1. Review of the Endocannabinoid System
    Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Jun;6(6):607-615. Hui-Chen Lu 1, Ken Mackie 2
  2. The Endocannabinoid System of Animals
    RJ Silver MDPI Sept., 2019
  3. Cannabinoid receptors in invertebratesJ. M. McPARTLAND,* J. AGRAVAL, D. GLEESON,à K. HEASMAN§ & M. GLASS J. EVOL. BIOL. 19 (2006) 366–373a 2005 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY
  4. Cannabinoid receptors are absent in insects
    J McPartland 1, V Di Marzo, L De Petrocellis, A Mercer, M Glass
    Comp Neurol. 2001 Aug 6;436(4):423-9. doi: 10.1002/cne.1078.
  5. The endocannabinoid system during development: emphasis on perinatal events and delayed effects
    Ester Fride 1, Nikolai Gobshtis, Hodaya Dahan, Aron Weller, Andrea Giuffrida, Shimon Ben-Shabat
    Vitam Horm. 2009;81:139-58. doi: 10.1016/S0083-6729(09)81006-6.
  6. Cannabinoid receptor 1/2 double-knockout mice develop epilepsy
    Epilepsia. 2017 Dec;58(12):e162-e166. doi: 10.1111/epi.13930. Epub 2017 Nov 3.
    Shane Rowley 1, Xiaofei Sun 2, Isabel V Lima 1 3, Alexandra Tavenier 2, Antonio Carlos Pinheiro de Oliveira 3, Sudhansu K Dey 2, Steve C Danzer 1 4

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