This randomized, controlled trial examined the safety of clavulanic acid (CLAV), a GLT-1 (astrocytic glutamate transporter) modulator, in combination with intravenous cocaine to determine whether CLAV can be safely studied in outpatients with cocaine use disorder who may continue to use cocaine. Participants were adults with moderate to severe cocaine use disorder planning to continue regular cocaine use. In a placebo controlled, crossover, inpatient study, the safety of 3 doses of oral CLAV (250 mg/day, 500 mg/day, and added later 750 mg/day) were studied in combination with 40 mg intravenous cocaine on a medical unit with close cardiac monitoring and pharmacokinetic sampling. Ten participants, 8 men and 2 women with cocaine use disorder, were studied with all participants receiving CLAV (250 mg, 500 mg, and placebo) and 5 participants receiving the additional 750 mg dose, in combination with cocaine. There were no clinically significant drug or dose related changes in vital signs, electrocardiogram intervals, pupillary diameters between CLAV and placebo. CLAV 500 mg decreased cocaine craving, using the 10 item Cocaine Craving Questionnaire-Brief, with a large effect size (Cohen’s d = 1.25). Thirty-two mild to moderate adverse events were recorded, with most drug related events being gastrointestinal. CLAV, at the doses of 250 mg, 500 mg, and 750 mg was reasonably well tolerated and safe in combination with intravenous cocaine. Associated adverse events were mild to moderate and resolved. CLAV 500 mg was associated with decreased craving for cocaine in people with cocaine use disorder.