Impaired verbal memory is common in MDMA (Ecstasy) polydrug users. The contributions of Ecstasy or polydrug exposure to reduced verbal memory are unclear, as is the neural basis for this cognitive deficit. Ecstasy users have reduced gray matter in brain regions mediating verbal memory (BA 18, 21 and 45). N-acetylaspartate (NAA) as a neuronal marker and myoinositol (mI) as a glial marker are inconsistently affected in Ecstasy users. We used 3 T MRS in 17 recreational drug users to test the hypothesis that Ecstasy polydrug use would be associated with altered NAA or mI in BA 18, 21 and 45. No effects were seen for mI. Metabolite ratios for NAA (mean+/-SD) were: BA 18-NAA/Cr (2.030+/-0.188); BA 21-NAA/Cr (1.861+/-0.325); BA 45-NAA/Cr (1.925+/-0.329). Lifetime cannabis use was significantly associated with BA 45 NAA/Cr (r=-0.687, p=0.014) but not with NAA in BA 18 or 21. In contrast, there were no statistically significant associations for lifetime use of Ecstasy, alcohol, or cocaine with NAA. These findings suggest that cannabis use may contribute to altered neuronal integrity in Ecstasy polydrug users in a brain region associated with verbal memory processing.