Objective:Cannabis use is associated with relative cognitive weaknesses as observed by cross-sectional as well as longitudinal research. Longitudinal studies, controlling for relevant confounds, are necessary to differentiate premorbid from post-initiation contributions to these effects.Methods:We followed a sample of adolescents and young adults across ten years. Participants provided neurocognitive data and substance use information at two-year intervals. Participants who initiated cannabis and/or alcohol use were identified (n = 86) and split into alcohol-only initiators (n = 39) and infrequent (n = 29) and moderately frequent (n = 18) cannabis initiators. Participants completed the Rey Auditory Verbal Learning Task (RAVLT) and the Iowa Gambling Task (IGT). Group differences before and after substance use initiation and the extent to which alcohol, nicotine, and cannabis use frequencies contributed to cognitive functions over time were examined.Results:After controlling for parental education, RAVLT new learning was worse in moderately frequent cannabis users prior to use initiation. RAVLT total learning and delayed recall showed significant declines from pre- to post-initiation in moderately frequent cannabis users. Regression analyses confirmed that frequencies of cannabis, but not alcohol, use contributed to post-initiation variations. Nicotine use showed an independent negative association with delayed memory. Findings for the IGT were not significant.Conclusions:Verbal learning and memory may be disrupted following the initiation of moderately frequent cannabis use while decreased new learning may represent a premorbid liability. Our use of a control group of alcohol-only users adds interpretive clarity to the findings and suggests that future studies should carefully control for comorbid substance use.