The findings from this study should be interpreted while considering the following limitations. Abstinence periods prior to imaging were variable, and although duration of abstinence did not correlate with FA or MD, delineation of the acute and chronic effects of marijuana and alcohol on white matter microstructure is of interest in follow-up studies. As alcohol use is so common among marijuana users, the specific effects of marijuana cannot be easily differentiated. Groups with singular substance use are difficult to obtain in naturalistic studies, but future work is needed to decipher the effects due to marijuana use alone versus combined MJ+ALC use on white matter alterations. Differences in diffusion properties between MJ+ALC users and non-users do not appear to be associated with premorbid functioning, as stable indicators of cognition were equal between groups and were unrelated to FA or MD. Despite this, pre-onset use white matter integrity in MJ+ALC users is unknown, and pre-existing vulnerabilities including increased incidence of behavioral dysregulation (Kirisci et al., 2004; Tarter et al., 2003) and negative affectivity (Chassin et al., 2004) may be associated with neurological
