Plant-derived, synthetic and endogenous cannabinoids as neuroprotective agents. Non-psychoactive cannabinoids, 'entourage' compounds and inhibitors of N-acyl ethanolamine breakdown as therapeutic strategies to avoid pyschotropic effects.
There is good evidence that plant-derived and synthetic cannabinoids possess neuroprotective properties. These compounds, as a result of effects upon CB(1) cannabinoid receptors, reduce the release of glutamate, and in addition reduce the influx of calcium following NMDA receptor activation. The major obstacle to the therapeutic utilization of such compounds are their psychotropic effects, which are also brought about by actions on CB(1) receptors. However, synthesis of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, which also have neuroprotective properties, are increased under conditions of severe inflammation and ischemia, raising the possibility that compounds that prevent their metabolism may be of therapeutic utility without having the drawback of producing psychotropic effects. In this review, the evidence indicating neuroprotective actions of plant-derived, synthetic and endogenous cannabinoids is presented. In addition, the pharmacological properties of endogenous anandamide-related compounds that are not active upon cannabinoid receptors, but which are also produced during conditions of severe inflammation and ischemia and may contribute to a neuroprotective action are reviewed.
Fowler
Christopher J
CJ
Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87, Umeå, Sweden. cf@pharm.umu.se
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002186:Cannabinoids / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D004983:Ethanolamines / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D011619:Psychotropic Drugs / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D000893:Anti-Inflammatory Agents; D002186:Cannabinoids; D004983:Ethanolamines; C022203:N-acylethanolamines; D018696:Neuroprotective Agents; D010936:Plant Extracts; D011619:Psychotropic Drugs; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug