Neuroprotection by Δ9-Tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity

M. Stelt, van der, W.B. Veldhuis, P.R. Bär, G.A. Veldink, J.F.G. Vliegenthart, K. Nicolaij

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Abstract

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.
Original languageEnglish
Pages (from-to)6475-6479
JournalJournal of Neuroscience
Volume21
Issue number17
Publication statusPublished - 2001

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