Raphael Mechoulam

Raphael Mechoulam (5 November 1930 – 9 March 2023) was an Israeli organic chemist recognized as a founder of modern cannabinoid research for isolating and determining the structures of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) from Cannabis sativa in the 1960s. His pioneering chemical analyses provided the empirical basis for subsequent pharmacological studies of these compounds, which demonstrated THC's psychoactive properties and CBD's non-intoxicating effects.

Born in Sofia, Bulgaria, to a Jewish family with a physician father, Mechoulam emigrated to Israel in 1949 amid post-World War II upheavals and pursued studies in chemistry at the Hebrew University of Jerusalem, earning an MSc in biochemistry and a PhD in organic chemistry. As a professor at the Hebrew University School of Pharmacy, he extended his investigations into the endogenous regulation of cannabinoid signaling, leading to the 1992 identification of anandamide (N-arachidonoylethanolamine), the first discovered brain constituent that binds to cannabinoid receptors, thus revealing the existence of an endocannabinoid system. Mechoulam's subsequent isolations, including 2-arachidonoylglycerol (2-AG), further mapped this lipid-mediated signaling pathway involved in physiological processes such as pain modulation and appetite regulation.

Mechoulam's contributions, grounded in structural elucidation and synthesis of over 60 cannabinoids, influenced therapeutic applications of cannabis derivatives, including synthetic THC analogs for nausea treatment in chemotherapy patients, while his lab's work emphasized causal mechanisms over anecdotal reports. He authored hundreds of peer-reviewed papers and received accolades like the Harvey Prize for his role in advancing medicinal chemistry, dying in Jerusalem at age 92 after a career spanning six decades.