Dr. Raphael Mechoulam, the grandfather of cannabis research!
Raphael Mechoulam (born in November 5, 1930 ) is an Israeli organic chemist and a professor of Medicinal Chemistry at the Hebrew University of Jerusalem in Israel. Raphael Mechoulam is best known for his work (together with Y. Gaoni) in the isolation, structure elucidation and total synthesis of THC the main active ingredient in cannabis and for the isolation and the identification of the endogenous cannabinoids anandamide in the brain and 2-arachidonoyl glycerol in peripheral organs
Initially, Raphael Mechoulam intended to study herbs in general, as evidenced by his library, which contains a wealth of texts on herbs from around the world. But the first plant he began to explore was, of course, Cannabis, and it took over his attention. the components of cocaine and opium were isolated in the 19th century, but when Raphael Mechoulam began his research, he discovered that the components of cannabis were unknown, despite it being one of the three most common drugs in the world at that time. The identity of one of its components, cannabidiol,CBD, had already been partially deciphered, but the psychoactive component was unknown. When he asked for a budget from the National Institutes of Health (NIH) research fund, he was rejected on the grounds that the issue was a big problem in the United States.
A year later, it was they who rushed to him because one of the senators in the US had caught his son smoking marijuana, and the father feared that the son’s brain would be permanently destroyed.
In the end ,Raphael Mechoulam, then at the Weizmann Institute of Science,together with Yechiel Geni and Habib Edri, isolated the active ingredient in cannabis, THC. It was then discovered that THC undergoes a chemical change in the body, and that the main product of the change, TH-hydroxy-7, has psychoactive activity. Moreover, the very use of cannabis increases the production of the enzyme responsible for this chemical change, which is why people who are exposed to the drug for the first time often do not feel any effect .
The Isolation of THC was only the first step. In the next stage Raphael Mechoulam and his colleagues went to investigate its mechanism of action in the body. The effect of a drug is that the body has another substance that the body produces itself (endogenous substance) and its natural effect is similar to that of the drug. Raphael Mechoulam therefore began to search for the natural endogenous substance with the similar effect to that of hashish. The first clue was that THC is an oily or lipophilic substance, which is soluble in the fatty tissues of the body, so it is likely that endogenous matter is also oily. At first, scientists believed that this substance worked in the body like anesthetics or organic solvents (also lipophilic) – that is, without a specific protein receptor. But that direction did not yield results.
At the end of the 1980s, evidence began to accumulate that the brain actually has a receptor that binds THC proteins and that the link to it causes psychoactive activity. If the receptor binds to THC, it also binds the endogenous cannabinoid,,. After quite a few technical difficulties, the team was able to trace the first endocannabinoid, and the question immediately arose: what name would be given to the new substance discovered. Bill Devan, then a postdoctoral student at Meshulam’s lab, proposed the name Anandamid, a combination of the word “ananda” which means supreme bliss in Sanskrit and the Amid chemical group. Anandamid did indeed cause great happiness to the researchers because their article has been cited 2,600 times
After the isolation of Anandamid, Meshulam’s group isolated the second endocannabinoid, known as 2-archidonyl glycerol (AG-2), and is now an extensive family of substances that include ethanol-rich fatty acids (such as anandamide) and amino acids with fatty acids, Although most of them, except Anandamide and AG, do not bind to the endocannabinoid receptors.
Today, at least two endocannabinoid receptors, CB1 and CB2, are known to be involved In a variety of biological processes, affecting every imaginable physiological system, such as the nervous system, the cardiovascular system, the reproductive system, and the immune system. Together, they are called endocannabinoid system and one of its main functions is to protect nerve cells. But they also affect anxiety, depression, cancer development, blood vessel expansion, bone building and even pregnancy.
Raphael Mechoulam stopped studying the cannabis plant 30 years ago, and chose to focus on the biological activity of endocannabinoids and their receptors. He has recently focused mainly on the CB2 receptor, which is more commonly found outside the central nervous system. “One of the things that fascinated me,” says Meshulam, “is that the receptor is closely linked to the immune system.
“The entire CB2 system is a defensive system,” says Meshulam. “Almost any problem you can think of in the body results in the appearance of CB2 receptors: myocardial infarction, blood blockage to the brain, cancer, inflammatory bowel disease, bone depletion, neurodegenerative diseases, allergies, etc. In all these cases, CB2 receptors pop up Days or even hours before the moment of the attack, and reduce the damage. ” Meshulam sees this as a parallel activity to the immune system. The immune system is directed against foreign proteins, while the endocannabinoid system works against internal injuries, such as fractures, damage or death of tissues. There is, of course, a close connection between the two systems.
Raphael Mechoulam’s research has revealed to the world of science a new signaling system, which is mobilized to act in the time and place required to help the body overcome injuries and tissue damage. Can we use it wisely? time will tell.