Topiramate-phentermine combinations reduce cocaine self-administration in humans

Rationale: Cocaine use disorder is an unrelenting public health concern. Despite nearly four decades of research, an FDA approved medication is not yet available. Objectives: The objective of this human laboratory study was to demonstrate the initial efficacy, safety and tolerability of topiramate-phentermine combinations for cocaine use disorder. Methods: Thirty-one (31) participants with cocaine use disorder completed this mixed-model inpatient laboratory study. Participants were maintained on topiramate (0 [N = 11], 50 [N = 9] or 100 [N = 11] mg/day). Each topiramate group was concurrently maintained on phentermine (0, 15, 30 mg). Drug self-administration, subjective responses and cardiovascular effects following acute doses of intranasal cocaine (0, 40, 80 mg) were determined during separate experimental sessions after at least seven (7) days of maintenance on each condition. Results: The three groups of participants were well matched demographically and generally did not differ significantly in their responses to a range of doses of intranasal cocaine (0, 10, 20, 40, 80 mg) during a medical safety session. Maintenance on topiramate and phentermine alone significantly decreased cocaine self-administration although these effects were modest in magnitude. Combining topiramate and phentermine robustly decreased cocaine self-administration. Topiramate and phentermine were well tolerated alone and combined, as well as in conjunction with cocaine. Conclusions: The results of the present study support advancing topiramate-phentermine combinations as a putative pharmacotherapeutic for cocaine use disorder.