The story of the Endocannabinoid System: The byproduct of discovering THC and CBD
If the average person were given a quiz to name one of the systems of the human body, the responses would range from some of the more well-known systems such as the nervous system, respiratory system, or digestive system, for example. What many do not know is that there is an additional system called the endocannabinoid system. If “endocannabinoid” sounds a little like “cannabis” to you, it’s because they are closely related. The endocannabinoid system was discovered in Israel by Dr. Raphael Mechoulam and his research team in 1992 after discovering the only active chemical in cannabis, which is delta-9-tetrahydrocannabinol (THC) in 1964.
Isolating THC + CBD
Dr. Raphael Mechoulam, also known as the “Grandfather of Cannabis Research”, is a renowned chemist and life-long researcher of the cannabis plant. In the early 1960s, Dr. Mechoulam knew that cannabis had been used for thousands of years, but the active compound that caused the physcoactive effects was never isolated in pure form.¹ This gap in universal understanding led Dr. Mechoulam down a rabbit hole that he continues to dig into to this day — understanding cannabis and its effects on the human body.
Using modern methods of the time, Dr. Mechoulam and his research team were able to isolate several compounds within cannabis. The compounds are called cannabinoids. They tested the novel cannabinoids on monkeys and then humans to find that only one cannabinoid had any effects on both groups of subjects. That compound was THC.¹ After this trailblazing discovery, Dr. Mechoulam and his team continued to test different cannabinoids for medicinal purposes. As their research continued, they further determined that there are over 100 different kinds of cannabinoids within cannabis, so they continued to isolate and test them. This process revealed that one of those cannabinoids, cannabidiol (CBD), stopped epileptic people from having seizures with zero psychoactive or undesired effects.¹ They continued to learn more about THC and CBD, which resulted in them publishing this research. The scientific research they completed was ahead of its time because it garnered no attention in the scientific community. Working in a small research lab in Israel, Dr. Mechoulam purposefully chose to work on cannabis because it was a research pathway (at the time) that was not being followed by major groups within the scientific community.¹ If they did not follow this strategy, larger research laboratories with sizeable budgets would be able to complete research at a faster pace than his intimate team in Israel. Due to this unique strategy, the lack of recognition from these remarkable research discoveries did not deter Dr. Mechoulam or his team. Instead, they posed another important research question — what is the scientific process of cannabinoids inside the human body? How do these cannabinoid compounds give mammals the desired effect? The answer to that question is located in the endocannabinoid system.
Discovering the Endocannabinoid System
Humans have cells in every part of our bodies and those cells are made up of different types of proteins. Located on the outside of cells, are receptor proteins. These receptor proteins recognize drugs and transmit the desired effect from outside the cell to the inside. During the mid 1980s, a group in the United States discovered the cannabinoid receptor number one (CB1 receptor), which was the first clue to uncovering the mechanism behind cannabis within the human body.¹ Then, cannabinoid receptor number two (CB2 receptor) was found, which led scientists to believe that our bodies and cannabinoids have something in common, they just did not know what that something was. Why do humans have receptors in our bodies for a smoked plant? With assistance from some of the top cannabinoid experts, Dr. Mechoulam and his research team made a discovery that would silently change the perspective of human anatomy. These receptors (CB1 + CB2) are located in our cells because humans produce compounds that mimic cannabinoids found in cannabis.¹ These compounds are called endocannabinoids which slightly differ from cannabinoids because endocannabinoids are endogenous compounds, while cannabinoids are exogenous. The endocannabinoids found in the human body that latch to CB1 and CB2 receptors are called Anandamide and 2-arachidonoyl glycerol (2-AG).² Anandamide is a naturally occurring endocannabinoid neurotransmitter found in the brains of mammals. When humans produce Anandamide, it latches to the CB1 receptor and humans feel happiness and bliss, similar to plant derived cannabinoids such as THC.² On the other hand, when humans produce 2-AG, it latches to the CB2 receptor to help certain ailments within the body. Humans produce 2-AG to help regenerate and protect their bodies when dealing with brain trauma, heart problems, strokes, arthritis, general pain, liver fibrosis, and neurodegenerative diseases.² Beyond these medical conditions, the endocannabinoid system is also involved in affecting anxiety, lack of appetite, blood pressure, the digestive system, the immune system, memory, and reproduction (not an exhaustive list).² Clearly, this relatively unfamiliar system helps us in many ways and provides a clear trail to understanding cannabis and its effects on our bodies.
Answers to unsolved scientific questions
Along with continued cannabinoid research spanning from medical findings in cannabis that showed improvements in PTSD, epilepsy, Graft vs. Host disease, and diabetes type 1, Dr. Mechoulam still has outstanding questions regarding the endocannabinoid system.²
1. Does the endocannabinoid system genetically define our personalities?
Everybody in the world has a different personality but science currently does not know what causes the distinct differences. Scientists understand that some of our personalities are influenced by our environment during our upbringing, but they don’t understand how our personalities are genetically created. Dr. Mechoulam’s speculation, after a lifetime of study, is that there are hundreds of endocannabinoid-like compounds in the brain. Due to this, everyone has a slightly different number of compounds that affect their personality based on genetics. Currently, there is no tangible evidence that supports this speculation, but it is an important research question for the future.¹
2. Is the endocannabinoid system involved in pregnancies?
When a woman becomes pregnant, the body should get rid of the embryo because 50% of it comes from a different organism (the man). The reason a woman’s body should reject the embryo is because foreign entities in the human body lower the immune system. For an unknown reason, the body does not reject the embryo and scientists do not know the cause for this. Dr. Mechoulam speculates that the endocannabinoid system is also involved in this immune effect that occurs within the embryo, which sustains life on earth.¹
References
1. The Scientist — The Story of Raphael Mechoulam and the Endocannabinoid System.; 2016. https://youtu.be/BE1XaQMRFA0. Accessed September 24, 2020.
2. Mechoulam R. The Cannabinoids: Looking Back and Ahead.
