Hippocampal neurotoxicity of Δ9-tetrahydrocannabinol

Guy Chiu Kai Chan, Thomas R. Hinds, Soren Impey, Daniel R. Storm

Research output: Contribution to journalArticlepeer-review

236 Scopus citations


Marijuana consumption elicits diverse physiological and psychological effects in humans, including memory loss. Here we report that Δ9- 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.

Original languageEnglish (US)
Pages (from-to)5322-5332
Number of pages11
JournalJournal of Neuroscience
Issue number14
StatePublished - Jul 15 1998
Externally publishedYes


  • Arachidonic acid
  • CB1
  • Cannabinoid receptors
  • Cell death
  • Hippocampal neurons
  • Reactive oxygen species
  • SR141716A
  • THC

ASJC Scopus subject areas

  • Neuroscience(all)


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