Author(s): S. Stevens Negus and Jack Henningfield
Cocaine addiction is a persistent and insidious public health problem. Despite evidence for sustained prevalence, clinical harm, and demand for treatment, the Food and Drug Administration (FDA) has yet to approve any pharmacotherapy. “Agonist” medications such as amphetamine maintenance have emerged as one intriguing but controversial class of candidates, and this Circumspectives Article presents pros and cons of agonist medications for treatment of cocaine use disorder from the perspectives of the empirical evidence and the regulatory challenges. Specifically, a substantial and growing body of evidence has been collected in laboratory animals, human laboratory studies, and clinical trials to support the potential therapeutic effectiveness of amphetamine and pharmacologically related “agonist” medications for treatment of cocaine use disorder. However, the use of these medications for this purpose would require FDA review and approval, and the path to FDA approval is impeded by significant obstacles. Drs. Negus and Henningfield discuss these issues and suggest future directions to (a) advance a candidate agonist medication toward FDA approval, and (b) clarify the mechanisms of action by which agonist medications reliably reduce cocaine consumption.