Chronic heavy cannabis use during adolescence is associated with an array of CMS alterations and potential neurocognitive consequences. The goal of the current study is to elucidate microstructural white matter integrity (WMI) to better understand the effects of cannabis on neuromaturation. The specific hypotheses are that increased levels of cannabis use will be associated with greater aberrancies in WMI and that decreased WMI will be associated with poorer cognitive performance. These hypotheses are based on evidence that 1) adolescent cannabis users consistently show an altered brain response to achieve intact task performance on neuropsychological measures, 2) the nature of the response is reflected in a more distributed functional network and recruitment of alternate and possibly compensatory brain regions and 3) cannabinoid receptors are known to exist in myelin precursors and to affect glial cell processing. Based on these observations, the aims of this proposal are to: 1) Use diffusion tensor imaging to characterize the relationship between adolescent cannabis use and WMI in regions with dense distributions of cannabinoid receptors. Adolescents with a history of heavy cannabis use will be examined after 28 days of monitored abstinence along with demographically similar non-users. We will compare the overall isotropic diffusivity and directional coherence within white matter fiber tracts using measures of mean diffusivity (MD) and fractional anisotropy (FA), respectively. 2) Define the relationship between WMI and neuropsychological test performance among cannabis users. Indices of WMI will be examined in relation to performance on measures of attention, learning and memory, psychomotor speed, and executive functioning, as well as substance use patterns. Preliminary data indicate that adolescent cannabis users show lower FA in the splenium of the corpus callosum when compared to their peers, and that increased cannabis use correlates with lower FA values. Here, we will identify FA values in regions that coincide with the functional networks previously described in this group, and correlate results with frequency of cannabis use and cognitive performance. Investigation of these relationships in young cannabis users is important for determining whether early exposure adversely affects myelin formation and the development of cortical projections necessary for complex processing. This information is prerequisite for an understanding of the link between the neurobiological and behavioral aspects of cannabis use. Further, understanding how cannabinoids influence neurodevelopment will inform public debate about the health effects of cannabis and how modulation of the endocannabinoid system may assist in the development of therapeutic tools. ? ? ?
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