According to a survey carried out by Medical Cannabis Evaluation in 2013, only 13% of medical schools in the United States teach the endocannabinoid system (ECS) as part of their curriculum. Why have medical institutions taken so little interest in such a vital system? The simple answer is ignorance. Decades of cannabis prohibition did a lot to hinder research on medicinal cannabis. Thankfully, we are now here and are getting acquainted with the important functions that are linked to the ECS.
The Long Trek to Freedom: Discovery of the Endocannabinoid System
The journey commenced in the middle of the 20th century and was a joint effort by a group of scientists. In the 1960s, Robert Mechoulam, an Israeli scientist, was keen on finding the healing compounds in the cannabis plant. Cannabis has been used as a medicinal compound for thousands of years, but the healing components of the plant had not been identified or investigated. In 1964, Dr. Mechoulam was successful in isolating delta-9-tetrahydrocannabinol (THC) as the first phytocannabinoid. He continued his research, and a few years later he was able to isolate the second cannabinoid, which was named cannabidiol (CBD). In 1986, Mechoulam published the book “Cannabinoids as Therapeutic Agents.” Here he outlined the therapeutic benefits of the cannabis plant, but at this point, it still was not clear how this plant was able to interact with the human body to perform healing.
Around 1988, Allyn Howlett and William Devane, through a US government-funded study, discovered endocannabinoid receptors in the mammalian brain. These receptors happened to be more abundant than any neurotransmitter in the brain.
Two years later, another team of scientists led by Lisa A. Matsuda isolated the DNA sequence of the first cannabinoid receptor, CB1, in a rat’s brain. Note that the ’90s was referred to as “the decade of the brain” because of the numerous advances in neuroscience that happened in this decade. The CB1 receptor was found to be concentrated in regions that control memory, motor coordination, appetite, thinking, emotions, and movement.
The CB2 receptor was identified soon after; it was found predominantly in the immune system and peripheral nervous system. This includes the gut, spleen, liver, lymph glands, endocrine glands, and reproductive organs.
In 1992, a team led by Israeli professor Dr. Mechoulam identified an endogenous molecule that interacts with the CB1 receptor. They named this endocannabinoid “anandamide,” which means bliss. In 1995, the second endocannabinoid was isolated and called – 2-arachidonoylglycerol, or “2-AG”; this molecule binds to both the CB1 and CB2 receptors. A third receptor has been identified and named GPR55; it has been associated with anti-cancer effects. The endocannabinoid system has been found in all mammals, reptiles and other animals apart from insects.
In summary, Robert Mechoulam wraps this journey up in such a beautiful way:
“By using a plant that has been around for thousands of years, we discovered a new physiological system of immense importance. We wouldn’t have been able to get there if we had not looked at the plant.”
Metabolic Enzymes Play a Significant Role
Apart from the endocannabinoids and their receptors, the other components that make up the ECS are metabolic enzymes. These enzymes play a key role in degrading endocannabinoids and removing them from the system once they have completed their functions. This ensures that anandamide and 2-AG do not accumulate in the system. It is hypothesized that should anandamide accumulate in the brain, it could cause euphoria in the same way that THC does. You can imagine “getting high” on your own “internal THC.” That’s why metabolic enzymes are crucial.
An enzyme called FAAH is responsible for breaking down anandamide, while another called MAGL is responsible for breaking down 2-AG. These three components make up the ECS, whose primary role is to maintain physiological balance in the body.
Endocannabinoids work in a backward fashion called retrograde signaling. This means that impulses are transmitted in the opposite direction. While other neurotransmitters are released from the presynaptic cell to postsynaptic cell, endocannabinoids are released from the postsynaptic cell and end up on receptors in the presynaptic cell. By acting this way, endocannabinoids are able to control the release of other neurotransmitters from postsynaptic cells. They work as a “dimmer switch” to control how and when other neurotransmitters are released.
The Endocannabinoid System and Homeostasis
Britannica defines homeostasis as “any self-regulating process by which biological systems tend to maintain stability while adjusting to conditions that are optimal for survival.”
Homeostasis helps the body to keep the body’s vital processes within certain parameters. This includes processes such as temperature control, hormonal regulation, hunger and appetite stimulation, and other important processes. When the body lacks homeostasis, diseases ensue. Restoring homeostasis helps in curing disease and treating symptoms of the disease. The ECS comes into play to help in supporting and restoring homeostasis. Some important functions regulated by the ECS are:
- Motor control
Now that there are fewer restrictions on cannabis research, we hope that the ECS will be demystified the more. This may mean more funding for cannabis research, larger clinical trials, and more evidence-based guidelines in the use of cannabis as a potential treatment for various diseases.
- Mediawix (2013): A Survey of American Medical School’s Acceptance of the Science of the ECS. Retrieved from http://media.wix.com/ugd/b72a4e_e88348b93436e74dea366be39a6b47e2.pdf
- Beyond THC: The Discovery of the Endocannabinoid System. Retrieved from https://www.beyondthc.com/wp-content/uploads/2012/07/eCBSystemLee.pdf
- Drug Library. org: Marijuana – The First Twelve Thousand Years. Retrieved from http://www.druglibrary.org/schaffer/hemp/history/first12000/1.htm
- NCBI (2013): Modulating the endocannabinoid system in human health and disease–successes and failures. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23551849/
- NCBI (2018): Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/