Neuroprotection by Delta(9)-tetrahydrocannabinol, the main active compoundin marijuana, against ouabain-induced in vivo excitotoxicity

Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative disease s. Here, we show in a longitudinal magnetic resonance imaging study that De lta (9)-tetrahydro-cannabinol (Delta (9)-THC), the main active compound in marijuana, reduces neuronal injury in neonatal rats injected intracerebrall y with the Na+/K+-ATPase inhibitor ouabain to elicit excitotoxicity. In the acute phase Delta (9)-THC reduced the volume of cytotoxic edema by 22%. Af ter 7 d, 36% less neuronal damage was observed in treated rats compared wit h control animals. Coadministration of the CB1 cannabinoid receptor antagon ist SR141716 prevented the neuroprotective actions of Delta (9)-THC, indica ting that Delta (9)-THC afforded protection to neurons via the CB1 receptor . In Delta (9)-THC-treated rats the volume of astrogliotic tissue was 36% s maller. The CB1 receptor antagonist did not block this effect. These result s provide evidence that the cannabinoid system can serve to protect the bra in against neurodegeneration.