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The Journal of Neuroscience, July 15, 1998, 18(14):5322-5332
Hippocampal Neurotoxicity of
 9-Tetrahydrocannabinol
Guy Chiu-Kai
Chan,
Thomas R.
Hinds,
Soren
Impey, and
Daniel
R.
Storm
Department of Pharmacology, University of Washington, Seattle,
Washington 98195
Marijuana consumption elicits diverse physiological and
psychological effects in humans, including memory loss. Here we report that  9-tetrahydrocannabinol (THC), the major
psychoactive component of marijuana, is toxic for hippocampal neurons.
Treatment of cultured neurons or hippocampal slices with THC caused
shrinkage of neuronal cell bodies and nuclei as well as genomic DNA
strand breaks, hallmarks of neuronal apoptosis. Neuron death induced by
THC was inhibited by nonsteroidal anti-inflammatory drugs, including
indomethacin and aspirin, as well as vitamin E and other antioxidants.
Furthermore, treatment of neurons with THC stimulated a significant
increase in the release of arachidonic acid. We hypothesize that THC
neurotoxicity is attributable to activation of the prostanoid synthesis
pathway and generation of free radicals by cyclooxygenase. These data suggest that some of the memory deficits caused by cannabinoids may be
caused by THC neurotoxicity.
Key words:
THC; cannabinoid receptors; CB1; cell death; hippocampal
neurons; arachidonic acid; reactive oxygen species; SR141716A
Copyright © 1998 Society for Neuroscience 0270-6474/98/18145322-11$05.00/0
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