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Modern marijuana research began in 1964 when Raphael Mechoulam isolated THC, defined its structure and confirmed it is the primary psychoactive chemical in marijuana. After Howlett and Devane demonstrated a cannabinoid receptor in the brain in 1988. Mechoulam isolated anandamide, the first endogenous cannabinoid discovered, 4 years later. The location of CB1 receptors throughout the brain was mapped by Herkenham and their unique presynaptic location discovered by Istvan Katona. The endocannabinoid system functions as a negative feedback homeostatic mechanism regulating the activity of the brain’s other neurotransmitters. Anandamide and 2-AG, the second and more numerous endocannabinoid discovered, are synthesized on demand from arachidonic acid found in cell membranes. Central to all these discoveries is the similarity in molecular structure between anandamide and THC. Researchers had discovered the physical mechanism by which marijuana affects the brain. By matching the f brain areas with high concentrations of cannabinoid receptors with their functions, the specific effect of THC’s mimicry of our natural chemistry began to make sense. The magic of marijuana is in the brain and not in the plant. Marijuana simply drives the endocannabinoid system far from its normal equilibrium.
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