HIPPOCAMPAL NEUROTOXICITY OF DELTA(9)-TETRAHYDROCANNABINOL

Marijuana consumption elicits diverse physiological and psychological effects in humans, including memory loss. Here we report that Delta(9) -tetrahydrocannabinol (THC), the major psychoactive component of marij uana, is toxic for hippocampal neurons. Treatment of cultured neurons or hippocampal slices with THC caused shrinkage of neuronal cell bodie s and nuclei as well as genomic DNA strand breaks, hallmarks of neuron al apoptosis. Neuron death induced by THC was inhibited by nonsteroida l anti-inflammatory drugs, including indomethacin and aspirin, as well as vitamin E and other antioxidants. Furthermore, treatment of neuron s with THC stimulated a significant increase in the release of arachid onic acid. We hypothesize that THC neurotoxicity is attributable to ac tivation of the prostanoid synthesis pathway and generation of free ra dicals by cyclooxygenase. These data suggest that some of the memory d eficits caused by cannabinoids may be caused by THC neurotoxicity.