Behavioral Economic Demand for Cocaine During Phendimetrazine Maintenance in Humans

Abstract

ObjectivesPhendimetrazine is a prodrug for the monoamine releaser phenmetrazine that has been investigated as a pharmacotherapy for cocaine use disorder. Preclinical studies indicate that phendimetrazine reduces cocaine self‐administration. Human laboratory research suggests that phendimetrazine may have limited abuse potential and has a favorable safety profile. However, the efficacy of phendimetrazine for reducing cocaine use in humans is unknown. Behavioral economic demand provides a fine‐grained measure of the relative reinforcing effects of drugs by accounting for the multi‐dimensional nature of reinforcement. The purpose of the present study was to use to evaluate behavioral economic demand for cocaine during phendimetrazine maintenance.MethodTwenty‐nine subjects completed a within‐subjects, placebo‐controlled, inpatient study. Subjects were maintained on oral phendimetrazine (210 mg/day) and placebo. After at least seven maintenance days on each dose, subjects completed a cocaine purchase task in which they were asked to indicate the hypothetical number of cocaine “hits” (i.e., 0.1 g cocaine) they would purchase at various prices/hit. Primary outcomes were two demand indices: 1) intensity (consumption at unconstrained price) and 2) elasticity (change in consumption with increased price). Intensity and elasticity were derived using the exponentiated demand equation. Demand curves were analyzed for nonsystematic data and then evaluated for phendimetrazine effects using linear mixed‐effects models. Demographic and substance use variables were also tested as moderators of treatment efficacy.ResultsThree‐criterion analysis indicated that 93% of demand curves were systematic. The exponentiated demand equation provided an excellent fit to curves under placebo (median R2 = .96) and active dosing (median R2 = .96), with no differences between dose conditions. Phendimetrazine did not alter cocaine demand elasticity (p = .91) or intensity (p = .12). However, BMI moderated the effects of phendimetrazine on intensity, with greater reductions in intensity observed for individuals with higher BMI.ConclusionsThese findings suggest that phendimetrazine maintenance does not universally alter cocaine demand, but may produce reductions in demand intensity for individuals with higher BMI. Future human laboratory studies and clinical trials that evaluate phendimetrazine for cocaine use disorder will be important for establishing the predictive validity of the cocaine purchase task for assessing therapeutic efficacy.Support or Funding InformationNational Institute on Drug Abuse (R01DA036553), National Center for Advancing Translational Sciences (UL1TR000117), and National Science Foundation (1247392).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.