Raphael Mechoulam - The Father of Cannabis Research

Stephen Andrews
05 Nov 2022

He is the scientist who has mastered research on the medical uses of Cannabis and who was the first to isolate tetrahydrocannabinol (THC) back in the 1960s. Dr. Raphael Mechoulam has spent decades studying and observing the therapeutic effects of Cannabis in patients suffering from epilepsy, cancer, Alzheimer's disease, chronic pain, and various other conditions. This November, he is turning 92.

Mechoulam's quest to unveil the greatest unknowns related to Cannabis stems from the desire to develop new medicines for diseases that have plagued humanity for so long. With his research team, he has also aimed to bridge the gap between Cannabis and the pharmaceutical industry. 

Throughout his decades-long career, Dr. Raphael Mechoulam has played a central role in some of the most significant discoveries about Cannabis. He is responsible for isolating THC and cracking the secrets of other cannabinoids, and along with his colleagues, he is also credited for having discovered endocannabinoids. These findings have launched a real revolution in medicine. 

Even into his advanced age, the outstanding scientist remained active in his field of research. Just a couple of years ago, he presented the discovery of cannabidiolic acid methyl ester (EPM301)⁠, a synthetic, fully stable acid-based cannabinoid molecule that could help shape the future of medicinal cannabis. 

Who is Raphael Mechoulam?

For those who don't know him, he is an Israeli and an outstanding organic chemist. He also has taught Medicinal Chemistry at the Hebrew University in Jerusalem, Israel. Born in Sofia, Bulgaria, he emigrated to Israel after the war, where he gained his first research experience as part of the Israeli army. He worked with insecticides. 

Mechoulam devoted much of his life to Cannabis research. In the 1960s, he and his colleagues were the first to synthesize THC. His work at the Weizmann Institute of Science led to the discovery of the human endocannabinoid system, which effectively earned him the title "Father of Cannabis Research." He is a founding member of the International Association for Cannabinoid Medicines (ICAM), which he also chaired between 2003 and 2005. 

Breakthrough Discovery

Perhaps much of the world's attention right now is on THC and CBD, however, these are only secondary compounds that are formed as a result of decarboxylation or heating. Cannabis plants initially contain acids, like THCA and CBDA, which were synthesized and also described in the 1960s, but never fully investigated. The reason is simple, acids are unstable. The compounds fall apart so easily that scientists can never be sure whether they are looking at an authentic acid structure or a derivative. 

However, Dr. Mechoulam's team managed to make another breakthrough there. A few years ago, they stabilized cannabidiol acids using a simple chemical reaction called esterification. This allowed the researchers to start a more thorough investigation on the effects of acid compounds and to confirm that they are much more powerful, with a huge potential to treat severe illnesses.

Why again is this so important? Mechoulam believes that Cannabis can be a substitute for a lot of synthetic pharmaceutical drugs. "We badly need new drugs in several diseases and some of the drugs that are available, may be pretty good but they ultimately cause side effects," he is noted as saying. "We have two groups of compounds today that need to have a replacement: these are steroids and opioids. We believe that cannabis carries the ability to introduce replacements to these families."

Views on Cannabis Research

Dr. Mechoulam has noted that there are three different stages of medicinal cannabis research. The first, he says, is phytochemistry, which refers mainly to the chemistry of the plant. Most people involved in Cannabis do participate in this type of research, i.e., on the compounds and materials that the plant produces. "These are things which we learned, described and tried to investigate with our research about 30 years ago, but since then many things have been happening," he said back in April 2019 while presenting a keynote speech at the ICBC International Cannabis Business Conference. 

He went on to say that the second phase is endocannabinoid research or investigation of the compounds of the cannabinoids that we make. "This was completed about 10 years ago, and since then, we have gone into the third phase of cannabinoid research and that is on the compounds that are more or less the same as the compounds we produce, but they have different effects," he said. 

Anandamide, a fatty acid neurotransmitter, was the first endocannabinoid to be discovered by Dr. Mechoulam and his lab members W.A Devane and Lumír Hanuš back in 1992. Another is 2AG, first described in the mid-1990s. The two have different chemical structures, but more importantly, they have the same physical properties as THC. They are lipids, dissolve only in fat, not water, act on the same receptors, etc. Unfortunately, there is a luck of drug testing to assess the full scale potential of anandamide and 2AG, even though this may be a complete game changer in treating depression, anxiety, and other diseases such as schizophrenia. 

Then again, it's worth remembering that it took three decades to prove the positive effects of Cannabis on patients with epilepsy. The mere publication of Mechoulam's research was not enough. There had to be pressure also from the parents of children with severe epilepsy who suffered from dozens of seizures a day. Eventually, indeed, cannabidiol was approved as a drug under the name Epidolex. The thirty-year time span is a reminder of how slow legislators and authorities can be when it comes to accepting Cannabis as a solution and the recommendations that scientists such as Mechoulam himself make. 

Countless Combinations to Explore

Just as there is anandamide, a fatty acid bound to an amino acid, there could be many other structures. For example, there are about 20 fatty acids and 20 amino acids in the body, from which other beneficial compounds could be formed. Exploring those other derivatives and structures is what the third phase of Cannabis research is. 

"We have a whole system, a lot of compounds that are very much involved in our physiology. At the moment most people are interested in cannabidiol and THC; the chances are as it happened with cannabidiol which had to wait for about 30 years, in 15 years from now most of the talks are going to be about endogenous cannabinoids, and on the cannabinoids which have more or less the same structure, but have different effects," says Mechoulam.

It's a promise for an exciting future of Cannabis research, and hopefully one where we don't have to wait for too long once we tap into the new depths of knowledge. 

Raphael Mechoulam turns 92 on November 5, 2022. Happy birthday, professor! Thank you for your life-long service to Cannabis science and the many things you and your team made possible!

Stephen Andrews