Raphael Mechoulam, a pioneering Israeli chemist who is credited with opening the field of cannabis science after identifying the structure and function of the key compounds of cannabis, died on March 9 at his home in Jerusalem. He was 92.
His death was confirmed by the American Friends of the Hebrew University. Professor Mechoulam had been on the university’s faculty since 1966.
Professor Mechoulam’s groundbreaking work with cannabis began in the early 1960s, just before the use of marijuana and other drugs exploded in countries around the world, bringing seismic changes to popular culture while also kicking off decades-long battles about health effects and enforcement. His research earned him the unofficial title “the father of cannabis research.”
In the beginning, Professor Mechoulam’s fascination with marijuana was not cultural but scientific, driven by a fascination with the chemical structures of plants and other natural products.
At the time, he found the science of cannabis to be sorely lacking. “Morphine had been isolated from opium in the 19th century, early 19th century,” Professor Mechoulam said in a 2014 interview with Dr. Sanjay Gupta, the chief medical correspondent for CNN. “Cocaine had been isolated from coca leaves mid-19th century. And here we were, mid-20th century, and yet the chemistry of cannabis was not known. So it looked like an interesting project.”
As a result, Professor Mechoulam and his team at the Weizmann Institute of Science in Rehovot, Israel, just south of Tel Aviv, began to break down the chemical structures of THC, the psychoactive compound in marijuana, to assess how it did what it did — namely, make users high. He continued this research for decades at the Hebrew University of Jerusalem.
He and his team were also able to illuminate the structure and effects of other cannabinoids, including cannabidiol, or CBD, a non-psychotropic component of the plant that has fueled a marketing craze in recent years because of its purported effectiveness in treating a variety of ailments, including anxiety, insomnia and chronic pain.
In his research at the Hebrew University, Professor Mechoulam synthesized many cannabinoid compounds that helped other scientists discover cannabinoid receptors in the brain, Yossi Tam, a professor at the Hebrew University and a longtime colleague, said in a phone interview.
Professor Mechoulam also did groundbreaking research on the body’s natural endocannabinoid system — including the discovery of anandamide, one of the main endocannabinoids. Endocannabinoids, chemicals similar to those found in marijuana, help regulate a wide range of bodily functions, including learning and memory, sleep, immune responses and appetite.
“Most of the human and scientific knowledge about cannabis was accumulated thanks to Professor Mechoulam,” Asher Cohen, the president of the Hebrew University of Jerusalem, said in a statement. “He paved the way for groundbreaking studies and initiated scientific cooperation between researchers around the world. Mechoulam was a sharp-minded and charismatic pioneer.”
This is not to say that there was much institutional hunger for such research in those pre-hippie days. “When we started work many years ago, there was essentially no interest in cannabinoids,” Professor Mechoulam said in a 2019 video interview. When he applied for a grant from the National Institutes of Health in the United States in the 1960s, he said, the agency responded: “When you have something more relevant to the U.S., contact us. Cannabis is not of interest. It’s used sometimes in Mexico, but not in the U.S.” (The N.I.H. would ultimately support his research for more than 40 years.)
“Well,” he added, “that changed quite fast.”
Raphael Mechoulam was born on Nov. 5, 1930, into a Jewish family in Sofia, Bulgaria. His father was a prominent Austrian-born physician, and his mother had studied in Berlin and encouraged a broad education in many languages.
After Bulgaria’s pro-German government passed a number of extreme antisemitic laws during World War II, “my parents believed that our family would be safer in small villages in the Balkans that badly needed physicians,” Professor Mechoulam wrote in a retrospective of his life and work published in the Annual Review of Pharmacology and Toxicology in January. “I recall my daily trips to the common village pump to bring home pails of water for our needs. And I read the few available books by sitting close to a candle in the evenings.”
His father was sent to a concentration camp in 1944 but survived. In 1949, the family emigrated to Israel, where Professor Mechoulam studied at the Hebrew University, earning a master’s degree in biochemistry. He was conscripted in 1953 and spent about two years working in an Israeli Army medical research unit.
After taking an academic post at the Weizmann Institute in the early 1960s, he began to read about the pharmacology of cannabis. “I was surprised to note that an active compound had apparently never been isolated in pure form, and that its structure was only partially known,” he wrote. “Even the structure of a major crystalline component, cannabidiol (CBD), which had been isolated more than two decades previously, was not fully elucidated.”
Because marijuana was illegal in Israel, Professor Mechoulam had to develop contacts within law enforcement to procure a supply for his studies. “I didn’t have a car at the time,” he told CNN. “I was in the bus carrying five kilos of hashish. People were just saying, ‘It’s kind of a strange smell.’ We tested that on a few volunteers, including ourselves.”
Back in the lab, he and a colleague, Yehiel Gaoni, “extracted the hashish and, by repeated column chromatography, were able to isolate about 10 compounds — most of them unknown — and elucidate their structures,” Professor Mechoulam wrote in the Annual Review.
Over the course of Professor Mechoulam’s career, Professor Tam said, he was a champion of research into the potential medical benefits of cannabis. In 1980, he conducted clinical research in Brazil, using CBD to treat people with epilepsy. After a few months, Professor Tam said, none of the people in the study reported seizures.
When Dr. Gupta of CNN referred to Professor Mechoulam, then in his 80s, as “the grandfather of marijuana,” Professor Mechoulam smiled and said, “Well, I am a grandfather, OK, I have seven grandchildren.” In addition to them, he is survived by his wife, Dalia (Borowitz) Mechoulam; his son, Roy Meshulam; and his daughters, Dafna Golan and Hadas Mechoulam.
In the 2019 video interview, Professor Mechoulam expressed his satisfaction with his contributions to science by quoting a poem by Rainer Maria Rilke, titled “Widening Circles”:
I live my life in widening circles
that reach out across the world.
I may not complete this last one
but I give myself to it.
“Well,” Professor Mechoulam said, “it is as if in some way he is describing what is going on with the cannabinoids. It started with a small circle, and expanded, and the expansion is going on and on and on.”
