Topiramate-phentermine combinations reduce cocaine self-administration in humans

Craig R. Rush, William W. Stoops, Joshua A. Lile, Joseph L. Alcorn, B. Levi Bolin, Anna R. Reynolds, Lon R. Hays, Abner O. Rayapati

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish
Article number108413
JournalDrug and Alcohol Dependence
Volume218
DOIs
StatePublished - Jan 1 2021

Bibliographical note

Funding Information:
This work was funded by a grant from the National Institute on Drug Abuse (NIDA) ( R01DA036827 ; T32DA035200 ) and the National Center for Advancing Translational Sciences ( UL1TR001998 ). These funding agencies had no role in study design, data collection, data analyses preparation of presentations, or submission of publications. Content is solely the responsibility of the authors and does not necessarily represent the official views of NIH.

Funding Information:
This work was funded by a grant from the National Institute on Drug Abuse (NIDA) (R01DA036827; T32DA035200) and the National Center for Advancing Translational Sciences (UL1TR001998). These funding agencies had no role in study design, data collection, data analyses preparation of presentations, or submission of publications. Content is solely the responsibility of the authors and does not necessarily represent the official views of NIH.

Funding Information:
The authors declare no relevant conflicts of interest. The authors gratefully acknowledge research support from the National Institute on Drug Abuse (R01DA036827; T32DA035200) and the National Center for Advancing Translational Sciences (UL1TR001998). These funding agencies had no role in study design, data collection or analysis, or preparation and submission of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2020

Keywords

  • Cocaine
  • Humans
  • Pharmacotherapy
  • Phentermine
  • Self-administration
  • Topiramate

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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