THE NON-PSYCHOTROPIC CANNABINOID (+)-(3S,4S)-7-HYDROXY-DELTA-6-TETRAHYDROCANNABINOL 1,1-DIMETHYLHEPTYL (HU-211) ATTENUATES N-METHYL-D-ASPARTATE RECEPTOR-MEDIATED NEUROTOXICITY IN PRIMARY CULTURES OF RAT FOREBRAIN

The non-psychotropic cannabinoid (+)-(3S,4S)-7-hydroxy-DELTA6-tetrahydrocannabinol 1,1-dimethylheptyl (HU-211), a stereoselective inhibitor of the N-methyl-D-aspartate (NMDA) receptor, protects primary cultures of rat forebrain against NMDA receptor-mediated neurotoxicity. Cell mortality produced by exposure for 10 min to NMDA or glutamate was reduced to approximately 18 or 27%, respectively, by application of 50 muM HU-211 for 10-15 min during or after exposure of cultures to excitatory amino acid. This effect of HU-211 was dependent on its concentration (EC50 = 8.7 +/- 4 muM). HU-211 also reduced the toxicity induced by brief exposure (10 min) to kainate or quisqualate, though less effectively. HU-211 may therefore prove useful as a non-psychoactive drug that protects against neurotoxicity mediated by the NMDA receptor.