The endocannabinoid system (ECS) is a biological system with ancient beginnings whose elements work throughout the body and brain to balance health and disease. Everything and everyone on Earth that has a backbone — vertebrates, in other words — has such a system.
The endocannabinoid system is related to cannabis because the ECS is the only reason cannabis works in the body and brain. But that’s not all it does. The endocannabinoid system works through three elements — enzymes, endocannabinoids, and receptors — all endogenous, meaning made in the body.
In the early 1990s, researchers found that a plant cannabinoid — the psychoactive cannabinoid THC, identified in 1964 — was binding to something in animals’ brains.
Knowing that molecules only work in the body if they can interact with or bind to a receptor, the researchers started looking for one, and eventually found two main receptors. And the researchers knew that if the brain had receptors that could bind a plant cannabinoid, there must also be endogenous (made in the body) THC-like molecules already in the body, and useful for things other than getting high on THC in cannabis.
Over time, scientists found the body’s own endocannabinoids. There are two main endocannabinoids, and for now we’ll just call them anandamide and 2-AG. Anandamide and 2-AG bind to the CB1 and CB2 receptors and in doing so they pass information through the cells that helps the body and brain coordinate their many biological functions.
Like the endocannabinoids, cannabinoids from cannabis bind strongly or weakly to the receptors, and this activation sends a specific message on to other cells, creating a cascade of messages that cause changes in the body and brain.
The third element of the endocannabinoid system are four main enzymes inside the cells that synthesize anandamide and 2-AG when they the body needs them and break down, or disassemble, the endocannabinoids after anandamide and 2-AG have had their effects.
We’ll examine the endocannabinoid system in more detail in HEALING WITH CANNABIS, where you’ll be surprised to learn that the endocannabinoid system works differently than almost any other biological system, and why evolution has conserved elements of the system across 1 billion or 2 billion years.
Dr. Maurice Elphick, a biologist and professor of physiology and neuroscience in the School of Biological and Chemical Sciences at Queen Mary University-London, says the ECS enzymes, at least a primordial version of them, first appeared in the earliest forms of life on Earth, possibly bacteria.
The enzymes, he said during a 2017 interview, go “way, way back, long before anything that we would describe as a cannabinoid receptor existed on Earth.” Elphick is an expert on the evolution of the ECS.
Time, as it does, passed.
Then, sometime after about 590 million years ago, all vertebrates, and even a couple of animals without backbones, arose on Earth with all you need for a complete endocannabinoid system: four main enzymes, two main endocannabinoids (anandamide and 2-AG) and two main receptors (CB1 and CB2). This was way before cannabis even existed, so cannabis isn’t the reason that the ECS evolved.
Flowering plants arose beginning at least 100 million years ago, and cannabis itself arose no earlier than 34 million years ago (McPartland JM, Nicholson J. Using parasite databases to identify potential nontarget hosts of biological control organisms. New Zealand J Botany. 2003;41(4):699-706.). Then about 5,000 years ago, cannabis showed up in the Chinese pharmacopeia as a treatment for a bunch of illnesses, and it spread around the world from there.
Lots more time passed, and scientists didn’t figure out that THC was the active (psychoactive) constituent of cannabis until 1964. The CB1 receptor was discovered around 1990 and CB2 in 1993. In 1992 the first endocannabinoid, anandamide, was discovered, and in 1995 they found the second one, 2-AG. And the four main enzymes were discovered in 1993, 2002, 2003 and 2004 (references for this paragraph are available in the book).
Even with all the essential elements identified, it took several years before the big picture started taking shape, which you can read about in HEALING WITH CANNABIS. And even though almost no one has heard much about the endocannabinoid system, it’s critical to health and disease in the body and brain.
The endocannabinoid system, neurologist and cannabinoid researcher Dr. Ethan Russo writes in a 2015 white paper (Russo EB, white paper, Jan 2015, Introduction to the Endocannabinoid System, corrected version. PDF), “is an essential regulatory mechanism in the body’s biochemistry and physiology, the basic machinery of everyday life.”