The Effect of Cannabis Use on Human Cerebellar Function

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DESCRIPTION (provided by applicant): Marijuana, or Cannabis sativa, is the most commonly used illicit drug in the United States. Increased levels of use occur during adolescence and young adulthood, which is of concern from a public health perspective, since these are also critical periods of neural development. This fear is further underscored by the fact that cannabis may act as a gateway drug, since its use may predispose individuals to abuse other illicit drugs. While it is well known that the active ingredient in cannabis, -9-tetrahydrocannabinol (THC) causes abnormalities in cognitive functions such as short-term memory and attention, there are a paucity of data examining the effect of cannabis use on the functional state of the cerebellum, a neural timing structure that is replete with cannabinoid receptors. Therefore, the overall aim of the current proposal is to examine whether current cannabis users demonstrate abnormalities in cerebellar-mediated classical eye blink conditioning (EBC) and paced finger tapping. In addition, assessments of the structural correlates of these deficits will be determined using magnetic resonance imaging (MRI). It is hypothesized that during the EBC paradigm cannabis users will demonstrate poorer learning performance (less and more poorly timed conditioned responses) as compared to controls. During the paced finger tapping tasks, it is predicted that cannabis users will exhibit increased tapping variability and increased tapping rates. It is also predicted that chronic cannabis users will exhibit decreased cerebellar volumes due to long-term endocannabinoid compensatory mechanisms, and that these volumetric changes will correlate with EBC and paced finger tapping performance. Finally, it is hypothesized that deficits in EBC, paced finger tapping, and cerebellar volume will correlate with the amount and length of cannabis use, including urinary levels of THC metabolites. Taken together, data from these studies will further our understanding of the cannabinoid system, which will help elucidate the mechanism of action of one of the most commonly used drugs of abuse.Project Narrative