He is one of the greatest in pharmaceutical chemistry: Israeli scientist Raphael Mechoulam is considered the discoverer of the essential active ingredients of the cannabis plant and their chemical structures, as well as the functioning of the human endocannabinoid system. The researcher, now 91, looks back on an eventful life – personally and in his role as a scientist.
Childhood in the Balkans
Raphael Mechoulam was born in Sofia, Bulgaria, in 1930. His father was considered a respected physician and was the director of the local Jewish hospital. Raphael attended an American elementary school in Sofia for the first half of his childhood and spent the second half in exile: after the Nazi threat, the Mechoulam family hid in various villages in the Balkans. The father was taken to a concentration camp in 1944, but fortunately survived captivity.
Emigration to Israel
After the end of World War II, the Mechoulam family emigrated to Israel. Raphael Mechoulam studied biochemistry at the Hebrew University in Jerusalem and received his doctorate in 1958. From 1953 to 1955, he had devoted himself to research on insecticides as part of his medical research work in the military service.
After receiving his doctorate, he obtained a postdoctoral position at the Rockefeller Institute in New York but returned to Jerusalem as early as 1960. There, at the Weizmann Institute, began the most important research path in Mechoulam’s life: the study of the active ingredients of the cannabis plant.
From 1966, Mechoulam worked at the Hebrew University in Jerusalem: first as a scientist, and later as a professor and rector of the university. In the 1990s, research visits and visiting professorships took him to the United States; Mechoulam also served as president of the ´International Cannabinoid Research Society´ from 1999 to 2000. He has received numerous awards, including the ´Israel Prize in Exact Sciences´ (2000) and the prestigious Harvey Prize, considered a precursor to the Nobel Prize (2020). The latter was awarded in recognition of Mechoulam’s pioneering discoveries in the field of medicinal cannabis.
Mechoulam still lives in Jerusalem and is still considered the most important pioneer in cannabis research.
Milestones in cannabinoid research: The merits of Mechoulam
1963/1964: Discovery of CBD and THC
- Mechoulam’s team obtains five kilograms of ´hashish´ needed for research purposes from the evidence room of an Israeli police station – presumably a seizure of contraband from Lebanon.
- Isolation of cannabidiol (CBD) as one of hundreds of active compounds in the hemp plant and description of its chemical structure. One year later, isolation of the psychotropic component tetrahydrocannabinol (THC), which is responsible for the intoxicating effect of cannabis.
First publication of the research team on the therapeutic effect of CBD in the following diseases:
- type 1 diabetes
- Autoimmune diseases
- Neurological diseases
Late 60s/early 70s: Research on monkeys
- Testing of major herbal cannabinoids for their effects in monkeys. Reconfirmation: THC has psychotropic effects on monkeys, but CBD does not.
1980: First double-blind study on the effects of CBD in epilepsy
- Start of research on the effects of CBD and THC on epilepsy – first on mice. Subsequently conducted a double-blind study on the effect of CBD in epilepsy patients with chronic symptoms with impressive results: After three months of therapy with CBD, there was either freedom from seizures or a significant reduction in seizures.
- The results of the study did not generate much interest in the research world or in the pharmaceutical markets, probably due to the stigma attached to cannabis.
1992: Unveiling of the endocannabinoid system (ECS)
- Identification of the endocannabinoids anandamide and 2-arachidonylglycero (2-AG), which the human body produces itself and which interact with CB1 and CB2 receptors.
- The research team observed similar interactions through the external delivery of cannabinoids and thus discovered the endogenous cannabinoid system, also called the endocannabinoid system (ECS).
- Knowledge of how the ECS works forms the basis for today’s therapeutic use of Cannabis sativa and the plant’s active ingredients.
2002: Traumatic brain injury research
- Discovery of increased production of anandamide and 2-AG in the brain after traumatic brain injury. In addition, the two endocannabinoids produced by the body inhibit the production of harmful substances after intracranial injury.
- Investigating the inhibitory potential of anandamide and 2-AG in neuronal damage after traumatic brain injury in mice and rats: Administration of the compounds significantly reduces the extent of brain damage.
We are especially thankful to Prof. Mechoulam for providing the picture for this article.
Mechoulam, R. (2022). A Delightful Trip Along the Pathway of Cannabinoid and Endocannabinoid Chemistry and Pharmacology. Annual Review of Pharmacology and Toxicology, 63(1). https://doi.org/10.1146/annurev-pharmtox-051921-083709