In Memoriam: Raphael Mechoulam Organic Chemist, Cannabis Pioneer 1931-2023
by Billee Sharp
The international cannabis community is mourning the passing of Raphael Mechoulam on the 9th of March 2023 at the age of 92. Widely recognized as the Grandfather of Cannabis Research, Mechoulam was the first to isolate the active compounds, THC, CBD and CBG and later led the team that discovered the endocannabinoids Anandamide and 2-AG . Anandamide comes from the Sanskrit word Ananda because there is not a good word in Hebrew for bliss. Mechoulam’s work laid the foundation of cannabinoid research which led to the discovery of the human Endocannabinoid System (ECS).
Mechoulam started researching cannabis in Israel in the 1960’s, he chose cannabis as his research topic because he had a tiny budget to work with and cannabis was not being studied anywhere else. He was aware that cannabis had been used therapeutically for thousands of years to treat many conditions and was still widely used in the U.S. in the early twentieth century, only being removed from the American Pharmacopeia in 1940.
In 1963 when he isolated Cannabidiol (CBD) Mechoulam decided to study the effects of CBD on epilepsy patients. The choice of epilepsy was a hunch Mechoulam had from reading a 15th century Arabic text which told the story of a prince who suffered from epilepsy; a doctor brought him cannabis which cured him, the only caveat was that the prince would have to take the medicine for the rest of his life.
The first CBD clinical trials were undertaken using mice, their epileptic seizures stopped while taking the CBD medication. In 1980 Mechoulam’s team went to Sao Paulo, Brazil to undertake human epilepsy clinical trials: the participants all had severe epilepsy which wasn’t responding to any other treatments. The patients were given a high dose of 200mg CBD daily and all participants experienced cessation of seizures, most participants became seizure-free while some experienced significant reduction in seizures.
In recent years Mechoulam continued to research and his team have just unveiled the final legacy of his work. EPM301 is a cannabidiolic acid methyl ester which is a secondary substance which occurs after the primary acid cannabinoids have been decarboxylated ( heated to 200˚C). Esterification creates a stabilized form for scalable production and is also significantly more potent than the primary cannabinoids. EPM301 has been approved for clinical trials in the U.S. for Irritable Bowel Syndrome (IBS), Psoriasis and Acute Respiratory Distress Syndrome (ARDS).
Mechoulam’s final project may be the key to cannabis medication finally entering the pharmaceutical domain and becoming widely accessible. It is also said that, of all his discoveries, the discovery of EPM301 is his most significant and will have the greatest impact towards creating a new approach to healthcare. At 90 years of age, he was still a pioneer, setting an example for aging with grace.
Throughout his long and remarkable career Mechoulam has supported cannabis research, co-founding both the International Cannabis Research Society and the International Association for Cannabinoid Medicines. He has been honored by many Universities and won many awards including the esteemed Harvey Award.
Mechoulam’s scientific work led the way for the shift in perspective where cannabis began to be seen as a medicinal plant rather than a recreational drug.
Many now hope that all of his incredible achievements will see Mechoulam posthumously awarded the Nobel Prize.
