Long-term abuse of marijuana by humans can induce profound behavioral deficits characterized by cognitive and memory impairments. In particular, deficits on tasks dependent on frontal lobe function have been reported in cannabis abusers. In the current study, we examined whether long-term exposure to delta9-tetrahydrocannabinol, the active ingredient in marijuana, altered the neurochemistry of the frontal cortex in rats. Two weeks administration of delta9-tetrahydrocannabinol reduced dopamine transmission in the medial prefrontal cortex, while dopamine metabolism in striatal regions was unaffected. These data are consistent with earlier findings of dopaminergic regulation of frontal cortical cognition. Thus, cognitive deficits in heavy abusers of cannabis may be subserved by drug-induced alterations in frontal cortical dopamine transmission.