This is the first study of the effect of topiramate on linguistic behavior and verbal recall using a computational linguistics system for automated language and speech analysis to detect and quantify drug-induced changes in speech recorded during discourse‐level tasks. Healthy volunteers were administered a single, 100‐mg oral dose of topiramate in two double-blind, randomized, placebo-controlled, crossover studies. Subjects' topiramate plasma levels ranged from 0.23 to 2.81μg/mL. We found a significant association between topiramate levels and impairment on measures of verbal fluency elicited during a picture description task, correct number of words recalled on a paragraph recall test, and reaction time recorded during a working memory task. Using the tools of clinical pharmacology and computational linguistics, we elucidated the relationship between the determinants of a drug's disposition as reflected in plasma concentrations and their impact on cognitive functioning as reflected in spoken language discourse.