Pioneering Israeli Cannabis Chemist Raphael Mechoulam has died

Every year since the passage of Prop 215 in 1996 inaugurated the era of medical marijuana, the growing cannabis community has seen its share of good news and bad news. And while there have been some deep disappointments already — such as the rejection of adult-use cannabis in Oklahoma — it’s doubtful much will top the passing of Israeli chemist Raphael Mechoulam, whose death in March was announced by Hebrew University, where he served as a professor. Since 1964, Mechoulam had either spearheaded or participated in numerous discoveries regarding the cannabis plant, and for decades stood at the forefront of knowledge not only of the cannabis plant, but the encocannabinoid system that responsds to its active compounds. If medical cannabis could be said to have a father, it would most likely be him. And while researchers the world over will continue in his footsteps, it will be without his guiding light and steadfast belief in the endocannabinoid system’s primacy in many of the world’s most intractable mental and physical disorders, and cannabis’s potential to treat many of them.

Born in 1930 in Sofia, Bulgaria to a physician father, Dr. Mechoulam’s life would be altered by the Second World War and the German government’s increasingly hostile treatment of Jews. Mechoulam’s father would eventually be sent to a concentration camp, an experience which he survived. Years later, Mechoulam’s life would be shaped with the realization that the UK’s cracking of the Enigma Code helped turn the tide of the war effort in North Africa against the presumably unbeatable Rommel. “Science saved my life and the lives of many others,” he recalled in a self-penned paper he wrote about his life, and it shaped the entire course of his future life.

Immigrating to Israel in 1949, Mechoulam continued his studies at Hebrew University, where he earned his masters. After a stint in the Israeli Army, where he worked on insecticides, he gained his PhD at the Weizmann Institute and did post-doctorate work at the Rockefeller Center in New York before accepting a position at Weizmann. There, he made his first major discovery in cannabis research: the discovery, isolation and structure of THC.

During his life, Mechoulam delighted in telling the story of how he initially received the cannabis for his groundbreaking work. Essentially, the administrative head of Weizmann knew a high-ranking member of the Israeli Police and vouched for Mechoulam’s character. From there, Mechoulam remembers, “I just went to Police headquarters, had a cup of coffee with the policeman in charge of the storage of illicit drugs, and got five kg of confiscated hashish, presumably smuggled from Lebanon.” From there, he not only discovered THC, but also published on the molecular structure of CBD as well.

However, perhaps his most consequential achievement wasn’t discovering the two most prominent molecules of cannabis, but in discovering the endocannabinoid system that recognizes them in the first place. That would take place 28 years later during Dr. Mechoulam’s time at Hebrew University. Working off the assumption that an endogenous cannabinoid would displace a radiolabeled cannabinoid probe from the CB1 receptor (a cannabinoid receptor discovered in the mid-1980s), Mechoulam and his colleague Bill Devane subjected candidates to several chromatography rounds for over a year before they discovered anandamide, named after the Sanskrit word for bliss. They would also discover another major endocannabinoid, 2-arachidonoyl glycerol, or 2-AG, several years later.

Up to the end of his life, Mechoulam pursued research on the effectiveness of cannabinoids, both endo- and exo-, and the role of the endocannabinoid system for several types of conditions. His research touched on addiction, cancer, bone formation and antimicrobial action against increasingly antibiotic-resistant bacteria. He repeatedly inveighed against the stigmas surrounding cannabis, believing that they stood in the way of people being helped by science. He often referred to a study he conducted with colleagues in São Paolo on CBD’s effectiveness in quelling seizures in children in 1980. While the results of the study showed great promise, with some patients reporting that their seizures dropped to nearly zero, virtually nothing happened with this information until medical cannabis activists in the 21st century petitioned GW Pharmaceutical to eventually create Epidiolex. He referred to this lost time ruefully in a speech he gave at CannMed in 2019, where he also announced a synthetically stable version of Cannabidiolic Acid. “Did we have to wait 30 years? No. We could have helped thousands of children, and we didn’t.”

Among his achievements, Mechoulam served as a founding member of the International Association of Cannabinoid Medicines and the International Cannabinoid Research Society. He received honorary doctorates from Ohio State University and Complutense University and received several awards during his lifetime, even having an award, the ICRS’s Mechoulam Award, named after him. His life’s work was also examined in the documentary The Scientist.