Cannabis Pioneer: Dr. Raphael Mechoulam

Missouri’s medical marijuana program is well underway in the Show-Me State, and many patients and advocates alike are aware of our journey to legalization as a medical-legal state.  Regardless, the cannabis conversation has been taking place for half a century in the world’s laboratories and notable cannabis pioneers have been driving progress and advocacy outside of our state’s borders, as well as our country’s property lines.

The clinician community supporting cannabis as medicine has been steadily growing over the past 40 years and perhaps the most notable figure with Ph.D. behind his name is likely Dr. Raphael Mechoulam.  Dr. Mechoulam has been referred to as the “father of cannabis research” since his initial findings of the endocannabinoid system (ECS) surfaced in the 1960s.  In 1964, Mechoulam brought 5 kilos of Lebanese hash given to him by the Israeli Police to his lab at the Weitzman Institute in Israel.  It was that hashish that would lead him to isolate and define tetrahydrocannabinol (THC) as a psychoactive component in cannabis. 

Mechoulam ascertained that THC interacts with the largest receptor system in the human body, the endocannabinoid system (ECS). His findings determined that the human brain produces its very own Cannabis – a chemical that they named anandamide after the Sanskrit word ananda, “bliss”.  Globally, chemists had been looking at cannabis since the 1930s, but the active compounds hadn’t been isolated to pure forms which prevented the full structure of the plant from being available for research.  Taking a page from other chemists’ playbook, Mechoulam reisolated cannabidiol (CBD) using that police-seized hash and then did the same isolation and synthesized THC. 

Further research over the next 50 years would lead to multiple discoveries and outcomes in the scientific community, and the ECS’s relationship with the cannabinoid compounds would demonstrate the therapeutic benefits of cannabis for maladies like pain from degenerative muscular diseases and treating nausea from chemotherapy with plant medicine. Based on the discoveries Mechoulam led, Israel’s Ministry of Health set up a program to provide approvals for certain patients to have access to medical cannabis. He’s been at the Hebrew University for 45 years, and though he retired 15 years ago his work and research have yet to come to a halt.

At 88, he continues to actively collaborate with scientists and students around the world to examine and synthesize a range of brain chemicals. Companies in Europe and Israel are eager to develop drugs based on this research and as society lessens the stigma associated with cannabis, those companies are banking on a huge return on investment by engaging in more research.

Mecholaum has been transparent in stating that there is a lack of sanctioned clinical research, which is a concern for him as a scientist.  He was quoted in an interview with the Israeli press as saying, “The regulations are still restricting research on cannabis.  More and more evidence is accumulating, but certainly not enough yet.  So many cancer patients around the world have used cannabis for years, but still, there is not even one randomized-controlled clinical trial with cancer patients.  

Every medication goes through clinical trials.  Hopefully, governments should be interested in this kind of data, but we know that governments, in general, don’t have the capacity needed to do such research.”  The average time for a drug to gain FDA approval is 12 years, yet as we’ve seen during the pandemic, there are certainly fast tracks available as the Covid-19 vaccine has proven. Dr. Mecholaum hasn’t stopped researching and discovering new medicinal applications for cannabis.

In 2020, his latest discovery, cannabidiolic acid methyl ester (EPM301) was announced as a patented compound, which is a synthetic, fully stable acid-based cannabinoid molecule.  For those of us without chemistry degrees, that means that THC and CBD while potent, are secondary products of the plant.  The acids are packed with compounds more potent than THC or CBD.  The acids in their native form are unstable, so Dr. Mecholaum found a way to stabilize them, and the stable compound has incredible potential for anxiety among other conditions.

As advocates, patients, and enthusiasts in the United States spend time working to legalize cannabis for recreation, and operators focus on new ways to cultivate and manufacture products that are high in THC for enthusiasts and educators work to push the importance of terpenes, Dr. Mecholaum will likely stay the course specific to medical research possibilities with his team and their future scientists. 

“I believe that the cannabinoids represent a medicinal treasure trove which waits to be discovered,” says Mechoulam today, as he did upon his original findings.