Raphael Mechoulam

Raphael Mechoulam (רפאל משולם, Рафаел Мешулам; 5 November 1930 – 9 March 2023) was a Bulgarian-born Israeli organic chemist and a professor in the Department of Natural Materials at the School of Pharmacy in the Faculty of Medicine of the Hebrew University of Jerusalem.

Mechoulam was born in Sofia, Bulgaria on 5 November 1930, to a Sephardic Jewish family.

Both parents were well-educated: his father was a physician and head of a local hospital and his mother had studied in Berlin.

He attended an "American grade school" in Sofia until the enactment of antisemitic laws and the beginning of World War II.

The school was closed.

Mechoulam's parents left Berlin, removing to a small village in the Balkans, where they hoped they would be safer.

In spite of being the only doctor in the area, Mechoulam's father was subsequently sent to a concentration camp, which he survived.

After the communist takeover of hitherto pro-German Bulgaria in 1944 he studied chemical engineering, which he "disliked."

In 1949 his family immigrated to Israel where he later studied chemistry.

Mechoulam received his M.Sc.

in biochemistry from the Hebrew University of Jerusalem in 1952.

During his military service in the Israeli Army from 1953 to 1956, he conducted research on insecticides.

In the years 1956–1958, Mechoulam did his doctorate at the Weizmann Institute of Science, and was one of the first to be awarded a doctorate by the Weizmann Institute.

The topic of his doctoral thesis was the synthesis of steroids and it was conducted under the guidance of Franz Sondheimer.

From 1959 to 1960, he did a post-doctorate at the Rockefeller Institute in New York in research on the structure of terpenes.

From 1960 to 1965, he worked as a researcher at the Weizmann Institute, and studied the chemistry of natural substances, including cannabinoids, terpenes, and alkaloids.

In 1963 Mechoulam began working on the components of the cannabis plant, from which hashish and marijuana are produced.

With other members of his research group including Yehiel Gaoni, Mechoulam elaborated the structures and stereochemistry of the major plant cannabinoids cannabidiol (CBD, 1963) and Δ9-tetrahydrocannabinol (THC, 1964) and succeeded in their total synthesis in 1965.

They also isolated, characterized and synthetized cannabigerol (CBG, 1964), and showed that it was not psychoactive.

In 1966, Mechoulam joined the faculty of the Hebrew University in Jerusalem.

In 1967, he received a research grant from the Institute of Mental Health in the United States to continue his research on hashish.

In 1968, he was appointed an associate professor, and in 1972, a full professor, at Hebrew University.

In 1970, Mechoulam's doctoral student Zvi Ben-Zvi reported the first isolation of an active THC metabolite in the human body.

In 1975 he was appointed to the Lionel Jacobson chair for medicinal chemistry.

Mechoulam served as Rector of the university from 1979-1982.

From 1979 to 1982, Mechoulam served as rector of the Hebrew University, and from 1983 to 1985 as pro-rector.

In 1982, he was a visiting professor at Ohio University, and in 1993–1994 he was a visiting professor in the Department of Pharmacology at the Richmond College of Medicine.

He was elected to the Israel Academy of Sciences and Humanities in 1994 and served as its scientific chair from 2007-2013.

In 1994, he was elected a member of the Israel Academy of Sciences and Humanities.

Mechoulam was a founding member of the International Association for Cannabinoid Medicines (IACM) and the International Cannabinoid Research Society.

He served as president of the International Cannabinoid Research Society from (1999–2002) and Chairman of the Board of the International Association for Cannabinoid Medicines (2003–2005).

He was a recipient of the Israel Prize for Chemistry Research in 2000 and the Harvey Prize for 2019-2020.

Known as "the godfather of cannabis research", Mechoulam is best known for his work (together with Y. Gaoni) in the isolation of tetrahydrocannabinol, or THC, the main active principle of cannabis.

He was also successful in the isolation and identification of the endogenous cannabinoids anandamide from the brain and 2-arachidonoyl glycerol, or 2-AG, from peripheral organs.

His work has led to the discovery of the endocannabinoid system, which has effects on many important aspects of human health.

From 2007 to 2018, he served as the chairman of the Natural Sciences Division at the Israel National Academy of Sciences.

Mechoulam died on 9 March 2023, at the age of 92.

Raphael Mechoulam's major scientific interest was the chemistry and pharmacology of cannabinoids.

Although cannabis had been the most widely used illegal drug in many parts of the world for centuries, its chemistry and biology were unknown, in contrast to morphine and cocaine, the two other common illegal drugs, which had been isolated as early as the 19th century.

While some research had been done, the psychoactive components of cannabis had not been isolated in their pure form, and their chemical structure had not been explained.