Rationale: Trichotillomania is characterized by repetitive pulling causing noticeable hair loss. Pharmacological treatment data for trichotillomania are limited. Objective: Dronabinol appears to reduce the exocitotoxic damage caused by glutamate release in the striatum and offers promise in reducing compulsive behavior. Methods: Fourteen female subjects (mean age = 33.3 ± 8.9) with DSM-IV trichotillomania were enrolled in a 12-week open-label treatment study of dronabinol (dose ranging from 2.5-15 mg/day). The primary outcome measure was change from baseline to study endpoint on the Massachusetts General Hospital Hair Pulling Scale (MGH-HPS). In order to evaluate effects on cognition, subjects underwent pre- and post-treatment assessments using objective computerized neurocognitive tests. Data were collected from November 2009 to December 2010. Results: Twelve of the 14 subjects (85.7%) completed the 12-week study. MGH-HPS scores decreased from a mean of 16.5 ± 4.4 at baseline to 8.7 ± 5.5 at study endpoint (p = 0.001). Nine (64.3%) subjects were "responders" (i.e., ≥35% reduction on the MGH-HPS and "much or very much improved" Clinical Global Impression scale). The mean effective dose was 11.6 ± 4.1 mg/day. The medication was well-tolerated, with no significant deleterious effects on cognition. Conclusions: This study, the first to examine a cannabinoid agonist in the treatment of trichotillomania, found that dronabinol demonstrated statistically significant reductions in trichotillomania symptoms, in the absence of negative cognitive effects. Pharmacological modulation of the cannabinoid system may prove useful in controlling a range of compulsive behaviors. Given the small sample and open-label design, however larger placebo-controlled studies incorporating cognitive measures are warranted.