Pharmacological and therapeutic secrets of plant and brain (endo)cannabinoids

Abstract

Research on the chemistry and pharmacology of cannabinoids and endocannabinoids has reached enormous proportions, with approximately 15,000 articles on Cannabis sativa L. and cannabinoids and over 2,000 articles on endocannabinoids. The present review deals with the history of the Cannabis sativa L. plant, its uses, constituent compounds and their biogeneses, and similarity to compounds from Radula spp. In addition, details of the pharmacology of natural cannabinoids, as well as synthetic agonists and antagonists are presented. Finally, details regarding the pioneering isolation of the endocannabinoid anandamide, as well as the pharmacology and potential therapeutic uses of endocannabinoid congeners are presented.

Cannabinoids and experimental models of multiple sclerosis

“…Wood and colleagues identified the first compound, cannabinol, in 1899 (Wood et al 1899). In 1963, Mechoulam and colleagues isolated cannabidiol (CBD) (Mechoulam and Shvo 1963), the most abundant nonpsychoactive cannabinoid derived from the plant (Hanus 2009). A year later, tetrahydrocannabinol (D 9 -THC), the major psychoactive component was first purified and structurally described by the same group (Gaoni and Mechoulam 1964).…”

“…THC mainly binds to CB1 receptor, whereas cannabinol preferentially acts through CB2 receptors (Hanus 2009). There is compelling evidence from CB1 and CB2 knockout mice in favour of the existence of additional cannabinoid receptors (Di Baskfield et al 2004;Garcia-Arencibia et al 2007).…”

“…Several additional, non-psychotropic cannabinoids were also documented at that time. The most known are: cannabigerol (CBG) (Mechoulam and Gaoni 1965), cannabichromene (CBC) (Hanus 2009), and cannabicyclol (CBL) (Crombie et al 1968). …”

“…Cannabinoids affect many biological functions from influencing short-term memory and motor coordination to mediating analgesia and inducing immunosuppression. Importantly, they exert most of their effects via interaction with cannabinoid receptors (Demuth and Molleman 2006;Di Marzo and Petrocellis 2006;Galal et al 2009;Hanus 2009). …”

“…In general, the endocannabinoid signaling system includes: (1) cannabinoid CB1 and CB2 receptors (2) endogenous agonists with high affinity to these receptors, of which anandamide and 2-arachidonoylglycerol are the best known to date and (3) specific molecular machinery for the synthesis, transport, and inactivation of these ligands (Pertwee and Ross 2002;Di Marzo and Petrosino 2007;Lambert 2007;Di Marzo 2008, 2009). Anandamide (Di Marzo et al 1994 and 2-AG (Di Bisogno et al 1997;Stella et al 1997) are produced in an inducible manner from lipid precursors, such as N-Arachidonoyl-phosphatidylethanolamine (NArPE) and diacylglycerols (DAGs), respectively (Fowler et al 2005).…”