Cannabinoids and prefrontal cortical function: insights from preclinical studies.

Marijuana use has been associated with disordered cognition across several domains influenced by the prefrontal cortex (PFC). Here, we review the contribution of preclinical research to understanding the effects of cannabinoids on cognitive ability, and the mechanisms by which cannabinoids may affect the neurochemical processes in the PFC that are associated with these impairments. In rodents, acute administration of cannabinoid agonists produces deficits in working memory, attentional function and reversal learning. These effects appear to be largely dependent on CB1 cannabinoid receptor activation. Preclinical studies also indicate that the endogenous cannabinoid system may tonically regulate some mnemonic processes. Effects of cannabinoids on cognition may be mediated via interaction with neurochemical processes in the PFC and hippocampus. In the PFC, cannabinoids may alter dopaminergic, cholinergic and serotonergic transmission. These mechanisms may underlie cognitive impairments observed following marijuana intake in humans, and may also be relevant to other disorders of cognition. Preclinical research will further enhance our understanding of the interactions between the cannabinoid system and cognitive functioning.