An open-label, dose run-up clinical trial of diethylpropion, a mild psychostimulant medication with an approved indication for the short-term treatment of exogenous obesity, was conducted in 10 cocaine dependent patients. A “cocaine agonist” strategy has been proposed as a potential pharmacotherapy to assist in the initiation of cocaine abstinence in severely dependent patients. Diethylpropion exhibits many of the desirable properties of a medication with cocaine agonist properties. The current trial was conducted to obtain preliminary data on the safety, tolerability and efficacy of diethylpropion in cocaine dependent patients. Moreover, the study was conducted to obtain guidelines for dosing in future clinical trials. The results of this preliminary study suggest possible anti-craving efficacy and mood elevating properties for diethylpropion in this population. However, side effects were noted. Although most were not of a serious nature, one involved the precipitation of a manic episode. Nevertheless, because of diethylpropion's potential clinical efficacy in this population, further cautious investigation of the efficacy of this medication for the treatment of cocaine dependence is indicated.