It has long been known that cannabis, the most widely used illicit substance (Johnston 2007), as well as naturally occurring and synthetic cannabinoids, impair learning and memory in humans and laboratory animals (Ranganathan and D'Souza 2006; Riedel and Davies 2005). Electrophysiological evidence suggests that the hippocampus plays a predominant role in the memory disruptive effects of marijuana. Δ9-tetrahydrocannabinoid (Δ9-THC), the primary psychoactive constituent of marijuana, and other cannabinoids activate cannabinoid-1 (CB1) receptors, which are widely distributed throughout the CNS, and are particularly abundant in the hippocampus (Matsuda, et al 1993). These compounds disrupt synaptic long-term plasticity in the hippocampus by reducing presynaptic neurotransmitter release (Misner and Sullivan 1999). Moreover, in vivo administration of Δ9-THC has been found to disrupt synaptic plasticity for up to three days (Mato, et al 2004).
