Endocannabinoids Part I: molecular basis of endocannabinoid formation, action and inactivation and development of selective inhibitors.
The discovery of specific receptors for Delta9-tetrahydrocannabinol, the major psychoactive component of marijuana, opened new horizons for the possible therapeutic exploitation of Cannabis sativa and the cannabinoids. Endogenous ligands of cannabinoid receptors, the 'endocannabinoids', were found and the molecular mechanisms underlying their biological effects and the regulation of their levels are now being identified. Cause/effect relationships between alterations of cannabinoid receptor/endocannabinoid levels in tissues and the symptoms of various pathological states are starting to be revealed. These studies may open the way to the possible use of substances that manipulate endocannabinoid levels and actions, such as inhibitors of the biosynthesis and inactivation and receptor antagonists, as cannabinoid-based therapeutic agents with little or no psychotropic side effect, thus potentially fulfilling an ambition nurtured for almost two centuries.
Istituto per la Chimica di Molecole di Interesse Biologico, Consiglio Nazionale delle Ricerche, Via Toiano 6, 80072, Arco Felice (NA), Italy. vdm@trinc.icmib.na.cnr.it
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