“The endogenous cannabinoid system – named for the plant that led to its discovery – is one of the most important physiologic systems 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. With its complex actions in our immune system, nervous system, and virtually all the body’s organs, the endocannabinoids are literally a bridge between body and mind. By understanding this system, we begin to see a mechanism that could connect brain activity and states of physical health and disease."
If you have not heard of the endocannabinoid system (ECS), don’t worry, you are not alone! Although discovered some three decades ago, it is only recently that its existence has become more widely known, and there are still many people who are unaware of this discovery. This includes some health professionals, who often refuse to prescribe medical cannabis (even to patients who have a legal right), due to concerns over safety because all they were taught in medical school was that cannabis was dangerous. And yet, scientists report that the importance of this system cannot be over-estimated due to the vital role it plays in our general health and well-being.
Medical training has historically included teaching about illicit drug abuse and how to treat addiction, so cannabis was grouped with narcotics such as heroin, LSD, ecstasy, and other equally dangerous drugs. And despite the discovery of the ECS (1992), and the subsequent publishing of more than 20,000 scientific papers reporting the role of cannabis in health, some three quarters of medical training institutions globally still fail to include teaching about the endocannabinoid system and its essential role in human health (1). And yet, ‘the ECS is the largest system in the human body, in charge of all other systems, and involved in almost all human diseases, disorders, ailments and their systems’ (2). So, while economic gain remains the primary reason for cannabis reform, it would not be happening without the discovery of the endocannabinoid system and the role cannabis plays in activating this system.
It is clear that Professor Mechoulam and his team knew, or strongly suspected, that cannabis was a healing plant by the early 1970s. This was when researchers published the first study showing the incredible effects THC had on cancer (1975). At the same time, a flurry of studies in the 1970s and early 1980s reported that cannabis could be a treatment for the eye disease glaucoma, and there was evidence showing CBD to have anti-psychosis and anxiolytic effects. Furthermore, a small clinical trial in 1980, published research showing a reduction in epileptic seizures in 7 out of 8 patients taking CBD, compare to 1 and 8 taking a placebo (3). As research continued, scientists found that the chemical compounds extracted from cannabis plants (THC and CBD), were able to provide relief to an array of symptoms and health conditions. The question was, how?
The breakthrough came in 1988, which is when researchers discovered that mammalian brains (so humans, animals, and fish), have receptor sites that respond to compounds in the cannabis plant. In this previously unknown molecular system, the researchers found receptors that were more numerous than any other neurotransmitter in the brain, and which appeared to be responsible for regulating a very wide range of biological functions (4). They named the receptors CB1 (cannabinoid 1). Then, on discovering a second receptor in 1990 (CB2), and further endogenous cannabinoids in 1992, they named the unknown molecular system the endocannabinoid system (ECS) after the plant that activated it – cannabis – and began studying its metabolic pathways (5).
The 100-Year Journey to Discovering the Endocannabinoid System
Timeline of the discovery of the endocannabinoid system:
- 1895: CBN is isolated and identified.
- 1930: Scientists figure out the structure of CBN, reporting that the cannabinoid has anti-inflammatory and anti-convulsant properties.
- 1940: Scientists isolate and identify CBD.
- 1963: Scientists identify the chemical structure of CBD
- 1964: Researchers isolate the cannabinoid tetrahydrocannabinol (THC), which they identify as being psychoactive and, as such, the part of the cannabis plants that makes a person ’high.’
- 1988: The first cannabinoid receptor (CB1) is discovered.
- 1990: Scientists report that they had mapped the DNA sequence that encodes the CB1 receptor and were able to clone the receptor. This led to research showing that THC works by activating CB1 receptors in the brain.
- 1990: Scientists find a second cannabinoid receptor (CB2) in the peripheral nervous system and immune system. The discovery of a second receptor leads scientists to find naturally occurring transmitters, which they name endocannabinoids. CB2 is encoded by the gene CNR2, consists of 360 amino acids. The rodent form of CB2 is about 80% identical. CB2 receptors occur mainly on immune cells, but also have been detected in the central nervous system, where they are associated with inflammation, addiction, and synaptic plasticity.
- 1992: The team of researchers working alongside Professor Mechoulam in Israel, report the discovery of the endocannabinoid anandamide. Shortly after, they discover a second major endocannabinoid – arachidonoylglycerol (2-AG), and later discovered the following endocannabinoids: homo-gamma-lineleoul, ethanolamide (DEA), docosatetraenoul, N-arachidonoyldopamin (NADA), and noladin ether (2-AGE).
- 1992: They announce the discovery of a new system in the body, which they named the endocannabinoid system.
Introducing Your Endocannabinoid System
“Receptors don’t exist because there’s a plant out there. Receptors exist because we, through compounds made in our body, activate them. So we went looking for the endogenous compounds that activate the cannabinoid receptors.”
(Professor Mechoulam when speaking at the 13th European Congress on Epileptology, 2018)
NOTE: At the time of writing this (Dec. 2020), a PubMed search for scientific journal articles published in the last 30 years containing the word “cannabis” revealed 19,079 results. Add the word ‘cannabinoid,’ and the results increase to 25, 696, which is the equivalent of 3.11 scientific studies being published every day in the past thirty years.
There are several well-known systems in the human body, such as our circulatory, respiratory, and reproductive systems, and they are all important – vital even. The endocannabinoid system (ECS), however, is “bigger than all the other systems in our bodies and more importantly, it is in charge of all the rest). This is because our ECS, which is a regulatory system, produces its own cannabinoids that are essentially responsible for maintaining balanced well-being and health – known as homeostasis – in our bodies.
The endocannabinoid system is involved in everything: from mood, hunger, inflammation, memory, sleep, reproduction, pain, and hunger is controlled by our endocannabinoid system. Cannabinoid receptors, which are resident in the cell membranes of connective nervous tissues and organs through the body, work with the system for curative effects as well as palliative ones: i.e. treating diseases as well as relieving symptoms. It really is a remarkable system.
Unfortunately, this important scientific discovery has only recently been divulged to the public, so it is for this reason that people are confused about the ‘sudden’ news of cannabis being some sort of miraculous healing plant. If the public had been informed that CB receptors had been found back in 1988 and 1990, and not kept out of the loop for almost 25 years, then we would have followed scientific progress and been aware the healing potential of the cannabis plant. Instead, cannabis was demonised by governments because they had chosen it to play the star – the leading role so to speak – in their so-called ‘War on Drugs.’
In the meantime, the U.S. was hedging its bets by secretly funding cannabis research, which led to it securing a patent, and some of the U.K’s leading politicians played a leading role in establishing and investing in GWP. Informing the public that cannabis was a healer, even a possible cure for cancer, was not, however, part of the U.K. government’s political agenda, and this information was withheld from the public and the war on drugs continued.
The research showing the potential of cannabis as medicine was largely ignored by the medical world during most of the 20th century, but this all changed with the discovery of the endocannabinoid system (CBS). In response, there was a flurry of research as scientists tried to discover more, thus leading to significant progress in the past couple of decades, and what they have found out is very exciting. Why? Because this strange unknown molecular system, our ECS, has turned out to be the biggest and most important system in the human body.
The endocannabinoid system is made up of receptors, metabolic enzymes, and endocannabinoids. It is responsible for homeostasis, which involves regulating the body so that you remain healthy and live comfortably. It controls many different physiological functions, such as eating, sleeping, and even social habits, and it also deals with health issues, e.g. pain, inflammation, body temperature, and skin diseases. The ECS helps the body’s neurons to navigate the neurotransmitters to the right receiver by either decreasing or increasing the level of endocannabinoids it creates so that imbalances are corrected. It is a very complex job and a big one, and there is still a lot that scientists do not know, but they continue to discover more as more and more research takes place across the world.
