Neuroprotective Effects of the Nonpsychoactive Cannabinoid Cannabidiol in Hypoxic-Ischemic Newborn Piglets

To test the neuroprotective effects of the nonpsy- choactive cannabinoid cannabidiol (CBD), piglets received i.v. CBD or vehicle after hypoxia-ischemia (HI: temporary occlusion of both carotid arteries plus hypoxia). Nonhypoxic-ischemic sham-operated piglets remained as controls. Brain damage was studied by near-infrared spectroscopy (NIRS) and amplitude- integrated electroencephalography (aEEG) and by histologic as- sessment (Nissl and FluoroJadeB staining). In HIvehicle, HI led to severe cerebral hemodynamic and metabolic impairment, as reflected in NIRS by an increase in total Hb index (THI) and a decrease in the fractional tissue oxygenation extraction (FTOE); in HICBD the increase of THI was blunted and FTOE remained similar to SHAM. HI profoundly decreased EEG amplitude, which was not recovered in HIvehicle, indicating cerebral hypofunc- tion; seizures were observed in all HIvehicle. In HICBD, however, EEG amplitude recovered to 46.4 7.8% baseline and seizures appeared only in 4/8 piglets (both p 0.05). The number of viable neurons decreased and that of degenerating neurons increased in HIvehicle; CBD reduced both effects by more than 50%. CBD administration was free from side effects; moreover, CBD administration was associated with cardiac, hemodynamic, and ventilatory beneficial effects. In conclusion, administration of CBD after HI reduced short-term brain damage and was associ- ated with extracerebral benefits. (Pediatr Res 64: 653-658, 2008)