Sumatriptan is a 5-HT1D agonist of therapeutic use in migraine and cluster headaches. To determine the profile of psychoactivity and abuse potential, a double-blind Latin-square crossover study was conducted in 12 male subjects with histories of substance abuse. The effects of subcutaneous placebo, sumatriptan (8 and 16 mg), and morphine (10 and 20 mg) were assessed on measures of subjective, behavioral, and physiologic responses including signs, symptoms, Addiction Research Center Inventory scales, onset of drug effects and miosis. Sumatriptan was psychoactive, was discriminated from placebo, produced a dose-related decrease on euphoria scores, elevated scores on measures of apathetic sedation and disliking, and lacked identification as a prototypic drug of abuse. There were no clinically significant effects on heart rate, pupil size, or blood pressure. In contrast, morphine (the positive control) produced expected dose-response relationships on measures of reinforcing and physiologic effects. The study suggests that sumatriptan has a low abuse potential.