Collectively, the results of the present study provide compelling evidence that Δ9-THC impairs memory function through a direct action of CB1 receptors in the hippocampus. Specifically, intrahippocampal administration of the CB1 receptor antagonist, rimonabant, completely blocked the disruptive effects of systemically administered Δ9-THC, the primary constituent responsible for marijuana's CNS effects, or the potent cannabinoid receptor agonist CP-55,940 in the radial arm maze task. Rimonabant's effects were regionally selective, as its infusion just outside the borders of the hippocampus failed to block Δ9-THC-induced memory impairment. While pharmacological antagonism of CB1 receptor signaling in the hippocampus blocked cannabinoid-induced memory impairment, it failed to attenuate other common cannabinoid pharmacological effects, including analgesia, motor alterations, and hypothermia. Likewise, intrahippocampal administration of CP-55,940 impaired spatial memory in the radial arm maze, without eliciting these other pharmacological effects (Lichtman, et al 1995). In conclusion, these findings support the hypothesis that CB1 receptors in the hippocampus are necessary for the memory disruptive effects of marijuana, but are not essential for the other common CNS actions of this drug.
