Mechoulam, Raphael

THC was first isolated from hashish in 1964 by Raphael Mechoulam (1930-) and Yehiel Gaoni at the Weizmann Institute. Mechoulam had obtained 5 kg hashish from Israeli police officials and the earliest scientific work on THC and cannabinoids used this source. In the early 1990s, the specific brain receptors affected by THC were identified. These receptors are activated by a cannabinoid neurotransmitter called arachidonylethanolamide, known as anandamide. Anandamide was named by Mechoulam using ananda, which is the Sanskrit word for ecstasy. Anandamide is thought to be associated with memory, pain, depression, and appetite. THC is able to attach to and activate anandamide receptors. These receptors are actually called THC receptors rather than anandamide receptors because researchers discovered that THC attaches to these receptors before anandamide was discovered. The areas of the brain with the most THC receptors are the cerebellum, the cerebral cortex, and the limbic system. This is why marijuana affects thinking, memory, sensory perception, and coordination. 

Matsuda, L. A., Lolait, S.J., Brownstein, M.J., Young, A. C., and Bonner, T. I. (1990). Structure ofa cannabinoid receptor and functional expression of the cloned cDNA. Nature 346, 561—564. McLaughlin, C. R., Martin, B. R., Compton, D. R., and Abood, M. E. (1994). Cannabinoid receptors in developing rats Detection of mRNA and receptor binding. Dmg Alcohol Depend. 36, 27—31. Mechoulam, R. (1986). Interview with Prof. Raphael Mechoulam, codiscoverer ofTHC. Interview by Stanley Einstein. Int. J. Addict. 21, 579-587. 

The main active principle of Cannabis, A -tetrahydrocan-nabinol, has been isolated and characterized by Raphael Mechoulam (Jerusalem, Israel) (Figure 1.44) in 1964. The term endocannabinoid coined after the discovery of membrane receptors for this psychoactive principle, indicates... 

By improved chromatographic methods, and thanks to the new techniques of NMR- and mass spectroscopy, Raphael Mechoulam at the Weizmann Institute of Science in Israel, succeeded in the 1960s in the isolation, structure elucidation and total synthesis of 4 -tetrahydrocannabinol, the pharmacological principle ofhemp. [126,127]... 

Starting from the thought that a lock had been discovered, there came now the question of the endogenous key . Altough A -tetrahydrocannabinol from hemp fits nicely into this lock it could be mere serendipity the more so as THC, unlike morphine, had not been detected in the human body as an endogenous compound. In 1992, Raphael Mechoulam (Fig. 5.67), at the Hebrew University in Jerusalem, discovered the first endocannabinoid, which he extracted from a pig s brain he demonstrated its affinity to the CBl-receptor by classical displacement studies. Mechoulam named it anandamide" (Sanskrit, ananda bliss). In chemical terms it is arachidonoylethanolamide (Fig. 5.68). Anandamide (Kj 52 nM) has practically the same affinity as A -tetrahydro-cannabinol (Kj 41 nM) at the CBl-receptor, but in contrast to THC, the former is rapidly deactivated hydrolytically by the enzyme anandamide amidohydro-lase. 

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