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Gambling disorder is a disabling illness experienced by 1% to 3% of adults. Pharmacologic management of gambling disorder has produced mixed results, with some but not all studies showing medication to be more effective than placebo. Ecopipam may offer promise for treating gambling disorder because of its antagonism of dopamine-1 receptors.Twenty-eight individuals with gambling disorder were enrolled and received ≥1 dose of oral ecopipam in an 8-week trial (1 week placebo lead-in, 6 weeks of medication (50 to 100 mg/d as needed), and 1 week follow-up. Participants were enrolled between September 2010 and June 2011 at 3 sites in the United States. Change from baseline to study endpoint on the Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure.Treatment was associated with statistically significant reductions in the PG-YBOCS total score (baseline score of 25.6 reduced to 14.0 at study endpoint; P.001) and PG-YBOCS subscales (Thought-Urge and Behavior, P.001).These findings suggest that pharmacologic targeting of the dopamine-1 receptor may be beneficial in gambling behavior. Placebo-controlled, double-blind studies are warranted to confirm these preliminary findings.