The purpose of the current study was to determine if self-reported lifetime marijuana use moderates the relationship between interleukin-6 (IL-6) and neurocognitive performance. Participants included 161 African American adults (50.3% women), with a mean age of 45.24 (SD=11.34). Serum was drawn upon entry into the study and participants completed a demographic questionnaire, which included drug use history, and a battery of neuropsychological tests. Using multiple regression analyses and adjusting for demographic covariates, the interaction term comprised of IL-6 and self-reported lifetime marijuana use was significantly associated with poorer performance on the Written (β=-.116; SE=.059; p=.049) and Oral trials (β=-.143; SE=.062; p=.022) of the Symbol Digit Modalities Test, as well as the Trail Making Test trial A (β=.157; SE=.071; p=.028). Current findings support previous literature, which presents the inverse relationship between IL-6 and neurocognitive dysfunction. The potential protective properties of marijuana use in African Americans, who are at increased risk for inflammatory diseases, are discussed.