By Ruth Hill R.N.

Professor Raphael Mechoulam is widely recognized as one of the greatest scientists in the field of cannabinoid research and was an active researcher up until his death. Born in Bulgaria together with his Jewish parents, he emigrated to Israel in 1949. He obtained an MSc in biochemistry in 1952 from the Hebrew University of Jerusalem, and subsequently a Ph.D. in chemistry from the Weizmann Institute in Rehovot, near Tel Aviv.

He then carried out postdoctoral research at the Rockefeller Institute in New York, before returning to The Hebrew University of Jerusalem in 1965, where he was appointed as Associate Professor in 1972 and as Professor of Medicinal Chemistry in 1975. It is at The Hebrew University where he began his prestigious cannabinoid research career.

Weed from the Police


While working as a chemist in the early 1960s at the Weizmann Institute, in Israel, Mechoulam got some weed from the Israeli police with his goal to discover and isolate what makes pot psychoactive. A medicinal chemistry professor his work laid the groundwork and got the ball rolling to prompt future breakthroughs, such as illumination into the human body’s internal cannabinoid receptors in the 1980s and ’90s. It is detailed in the 1993 academic paper titled Molecular characterization of a peripheral receptor for cannabinoids.

For nearly two decades after the identification of THC in the plant marijuana, its mechanisms of action were believed to be entirely “non-specific”. However, in the 1980s, findings obtained by several research groups suggested there was more to investigate.

Finding The Endocannabinoid System

Mechoulam encouraged a search for a cannabinoid receptor in mammalian tissues, and this search led to the discovery of two G protein-coupled cannabinoid receptors, the first (CB1) discovered between 1988 and 1990. The second (CB2) was discovered in 1993.

The evidence obtained in the late 1980s that mammalian tissues express the CB1 receptor immediately prompted searches for a chemical produced by these tissues that can activate this receptor. The race to discover such an “endocannabinoid” was won by Mechoulam. He led research that provided convincing evidence that N-arachidonoyl ethanolamine, which he and his collaborators named anandamide, after the Sanskrit word ananda or “bliss”, is an endogenously produced compound that can activate the CB1 receptor. He also discovered the endocannabinoid receptor-activating the CB2 receptor CBD or (2-arachidonoylglycerol).

Mechoulam decided to look for endocannabinoids among endogenous lipophilic compounds rather than endogenous peptides, even though certain peptides, named endorphins, had already been found. Other lipophilic endocannabinoids were also subsequently discovered. Among Raphael Mechoulam’s many other achievements are the design and synthesis of numerous important novel cannabinoids that serve as valuable experimental tools or have important therapeutic potential.

Meet EPM301

“EPM developed a method to work with the original substances of cannabis,” the Professor explained in a recent exclusive interview. “So, while everybody is discussing THC and CBD, these cannabinoids are actually a secondary substance; they only appear later in the plant.” Mechoulam’s recent revelation stems from the development of a method that allows the modification of acids in a way that keeps them stable enough to allow for their large-scale use. This opens the door for further pharmaceutical experiments, the professor explained. Dr. Mechoulam shared the history of the journey behind this revolutionary process and its significance in evolving the use of CBD as a pharmaceutical drug.

However, these cannabidiolic acids were unstable, and therefore useless in pharmaceutical drug development. Until now, that is. “Originally there is an acid that appears in the plant, and those acids are these mysterious worlds of compounds that are much more potent than cannabinoids,” he added. Strict drug laws in the United States and around the world suppressed research and kept the derivatives of cannabis off the market. Watch a video of Mechoulam on YouTube.

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