CannabinoidsRoger G. Pertwee Less than 20 years ago the ?eld of cannabis and the cannabinoids was still c- sidered a minor, somewhat quaint, area of research. A few groups were active in the ?eld, but it was already being viewed as stagnating. The chemistry of cannabis 9 9 was well known, ? -tetrahydrocannabinol (? -THC), identi?ed in 1964, being the only major psychoactive constituent and cannabidiol, which is not psychoactive, possibly contributing to some of the effects. These cannabinoids and several s- thetic analogs had been thoroughly investigated for their pharmacological effects. Their mode of action was considered to be non-speci?c. The reasons for this - sumption were both technical and conceptual. On the technical side, it had been shown that THC was active in both enantiomeric forms (though with a different level of potency) and this observation was incompatible with action on biological substrates—a receptor, an enzyme, an ion channel—which react with a single stereoisomer only. The conceptual problem related to THC activity. This had been pointed out by several highly regarded research groups that had shown that many of the effects seen with cannabinoids were related to those of biologically active lipophiles, and that many of the effects of THC, particularly chronic ones, were comparable to those seen with anaesthetics and solvents. |
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2-arachidonoylglycerol acid amide hydrolase activity adenylyl cyclase affinity analogs anandamide antinociception basal ganglia binding Biochem Bisogno Brain Res Ca2+ cannabidiol cannabinoid agonists cannabinoid CB1 receptor cannabinoid receptor cannabinoid receptor agonists cannabis capsaicin CB₁ CB1 and CB2 CB1 cannabinoid receptor CB1 receptor CB1R cells chronic compounds concentrations decrease dopamine dose drug effects of cannabinoids endocannabinoid signalling endocannabinoid system endogenous cannabinoid enzyme expression FAAH fatty acid amide Fernández-Ruiz function GABAergic glutamate Herkenham hippocampus human increased induced inhibition inhibitors interaction inverse agonist kinase knockout mice levels ligands Makriyannis marijuana Martin Marzo mechanism Mechoulam mediated membrane metabolism modulation Mol Pharmacol molecular mouse mRNA Natl Acad Sci neurons Neurosci neurotransmitter noid pain pathways peripheral Pertwee RG Petrocellis Pharmacol Exp Ther pharmacological Piomelli postsynaptic potential presynaptic Proc Natl Acad protein-coupled rat brain receptor antagonist release response Rinaldi-Carmona role spinal stimulation studies synaptic tetrahydrocannabinol THCCOOH tissue transmission TRPV1 vanilloid vitro vivo