Raphael Mechoulam is an Israeli organic chemist and professor of Medicinal Chemistry at the Hebrew University of Jerusalem in Israel. He is best known for his work (together with Y. Gaoni) in the isolation, structure elucidation and total synthesis of Δ9-tetrahydrocannabinol, the main active principle of cannabis and for the isolation and the identification of the endogenous cannabinoids anandamide from the brain and 2-arachidonoyl glycerol (2-AG) from peripheral organs together with his students, postdocs and collaborators.
Over the last few decades research on the cannabinoids has gone through several distinct phases:
A. Plant cannabinoids. While many dozens of plant cannabinoids are known today, most research is still on THC and CBD. THC has been approved as a drug for enhancement of appetite, and is also used to prevent vomiting due to cancer chemotherapy. However of particular interest is CBD, which does not cause the typical cannabis psychoactivity, but is a potent anti- epileptic drug and is used in many countries in pediatric epilepsy. It is being evaluated in other therapeutic areas (graft versus host disease, schizophrenia, autoimmune diseases).
B. Endogenous cannabinoids. The endogenous cannabinoids anandamide and 2-arachidonoyl glycerol (2-AG) were discovered in the 1990’s. Both compounds bind to the cannabinoid receptors CB1 and CB2. They are involved in a very large number of diseases, mostly as neuroprotective entities. However neither anandamide nor 2-AG have been administered to humans and although they are highly promising as potential drugs clinical trials have to be undertaken.
C. Anandamide-like endogenous fatty acid amides with amino acids and ethanol amines. A large number of compounds of these types have been discovered in the brain and other tissues, and some of them have been shown to be of major importance in a large spectrum of biological functions and diseases. Thus, oleoyl serine is an anti-osteoporotic molecule, arachidonoyl serine is a vasodilator and lowers brain damage and oleoyl glycine has anti addiction properties.