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ARTICLE

Hippocampal Neurotoxicity of Δ9-Tetrahydrocannabinol

Guy Chiu-Kai Chan, Thomas R. Hinds, Soren Impey and Daniel R. Storm
Journal of Neuroscience 15 July 1998, 18 (14) 5322-5332; DOI: https://doi.org/10.1523/JNEUROSCI.18-14-05322.1998
Guy Chiu-Kai Chan
1Department of Pharmacology, University of Washington, Seattle, Washington 98195
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Thomas R. Hinds
1Department of Pharmacology, University of Washington, Seattle, Washington 98195
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Soren Impey
1Department of Pharmacology, University of Washington, Seattle, Washington 98195
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Daniel R. Storm
1Department of Pharmacology, University of Washington, Seattle, Washington 98195
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Abstract

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.

  • THC
  • cannabinoid receptors
  • CB1
  • cell death
  • hippocampal neurons
  • arachidonic acid
  • reactive oxygen species
  • SR141716A
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The Journal of Neuroscience: 18 (14)
Journal of Neuroscience
Vol. 18, Issue 14
15 Jul 1998
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Hippocampal Neurotoxicity of Δ9-Tetrahydrocannabinol
Guy Chiu-Kai Chan, Thomas R. Hinds, Soren Impey, Daniel R. Storm
Journal of Neuroscience 15 July 1998, 18 (14) 5322-5332; DOI: 10.1523/JNEUROSCI.18-14-05322.1998

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Hippocampal Neurotoxicity of Δ9-Tetrahydrocannabinol
Guy Chiu-Kai Chan, Thomas R. Hinds, Soren Impey, Daniel R. Storm
Journal of Neuroscience 15 July 1998, 18 (14) 5322-5332; DOI: 10.1523/JNEUROSCI.18-14-05322.1998
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Keywords

  • THC
  • cannabinoid receptors
  • CB1
  • cell death
  • hippocampal neurons
  • arachidonic acid
  • reactive oxygen species
  • SR141716A

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