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The Journal of Neuroscience, September 1, 2001, 21(17):6475-6479

Neuroprotection by ⁹-Tetrahydrocannabinol, the Main Active Compound in Marijuana, against Ouabain-Induced In Vivo Excitotoxicity

M. van der Stelt¹, W. B. Veldhuis^{2, 3}, P. R. Bär³, G. A. Veldink¹, J. F. G. Vliegenthart¹, and K. Nicolay²

¹ Department of Bio-Organic Chemistry, Bijvoet Center for Biomolecular Research, 3584 CH, Utrecht University, Utrecht, The Netherlands, ² Department of Experimental In Vivo NMR, Image Sciences Institute, 3584 CJ, Utrecht, University Medical Center Utrecht, The Netherlands, and ³ Department of Experimental Neurology, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands

Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases. Here, we show in a longitudinal magnetic resonance imaging study that ⁹-tetrahydrocannabinol (⁹-THC), the main active compound in marijuana, reduces neuronal injury in neonatal rats injected intracerebrally with the Na⁺/K⁺-ATPase inhibitor ouabain to elicit excitotoxicity. In the acute phase ⁹-THC reduced the volume of cytotoxic edema by 22%. After 7 d, 36% less neuronal damage was observed in treated rats compared with control animals. Coadministration of the CB₁ cannabinoid receptor antagonist SR141716 prevented the neuroprotective actions of ⁹-THC, indicating that ⁹-THC afforded protection to neurons via the CB₁ receptor. In ⁹-THC-treated rats the volume of astrogliotic tissue was 36% smaller. The CB₁ receptor antagonist did not block this effect. These results provide evidence that the cannabinoid system can serve to protect the brain against neurodegeneration.

Key words: anandamide; astrogliosis; cannabinoid; excitotoxicity; magnetic resonance imaging; neonatal rat; neuroprotection; ouabain; THC

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21176475-05$05.00/0

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