Δ 9 ‐tetrahydrocannabinol increases endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons: Involvement of CB 1 receptors

The effects of the principal psychoactive component of marijuana, Δ 9 ‐tetrahydrocannabinol (Δ 9 ‐THC), on endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons were investigated. Locally applied Δ 9 ‐THC (0.03, 3, 300, and 1,000 nM) concentration‐dependently increased basal extracellular glutamate levels (+18% ± 11%, +54% ± 10%, +90% ± 14%, +149% ± 33% vs. basal). The facilitatory effects of Δ 9 ‐THC (3 and 300 nM) on cortical glutamate were fully counteracted in the presence of the selective CB 1 receptor antagonist SR141716A (10 nM) and by replacement of the normal Krebs‐Ringer bicarbonate buffer with a low‐Ca 2+ (0.2 mM) medium. Δ 9 ‐THC application also induced an enhancement in K + ‐evoked glutamate levels. These findings suggest that an increase in cortical glutamatergic transmission mediated by local CB 1 receptor activation may underlie some of the psychoactive and behavioral effects of acute marijuana consumption. © 2002 Wiley‐Liss, Inc.