Cannabinoids and brain injury: therapeutic implications.
Mounting in vitro and in vivo data suggest that the endocannabinoids anandamide and 2-arachidonoyl glycerol, as well as some plant and synthetic cannabinoids, have neuroprotective effects following brain injury. Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission and reduce the production of tumour necrosis factor-alpha and reactive oxygen intermediates, which are factors in causing neuronal damage. The formation of the endocannabinoids anandamide and 2-arachidonoyl glycerol is strongly enhanced after brain injury, and there is evidence that these compounds reduce the secondary damage incurred. Some plant and synthetic cannabinoids, which do not bind to the cannabinoid receptors, have also been shown to be neuroprotective, possibly through their direct effect on the excitatory glutamate system and/or as antioxidants.
Mechoulam
Raphael
R
Dept of Medicinal Chemistry and Natural Products, Medical Faculty, Hebrew University, Jerusalem 91120, Israel. mechou@cc.huji.ac.il
Panikashvili
David
D
Shohami
Esther
E
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D063388:Endocannabinoids; D005989:Glycerides / Q000494:pharmacology; D006801:Humans; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D053284:Polyunsaturated Alkamides; D051381:Rats
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D005989:Glycerides; D018696:Neuroprotective Agents; D053284:Polyunsaturated Alkamides; D013759:Dronabinol; C094503:glyceryl 2-arachidonate; C062018:HU 211; C078814:anandamide