Naltrexone-bupropion combinations do not affect cocaine self-administration in humans

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

Research output: Contribution to journalArticlepeer-review


The FDA has not yet approved a pharmacotherapy for cocaine use disorder despite nearly four decades of research. This study determined the initial efficacy, safety, and tolerability of naltrexone-bupropion combinations as a putative pharmacotherapy for cocaine use disorder. Thirty-one (31) non-treatment seeking participants with cocaine use disorder completed a mixed-design human laboratory study. Participants were randomly assigned to the naltrexone conditions (i.e., 0, 50 mg/day; between-subject factor) and maintained on escalating doses of bupropion (i.e., 0, 100, 200, 400 mg/day; within-subject factor) for at least four days prior to the conduct of experimental sessions. Cocaine self-administration (IN, 0, 40, 80 mg) was then determined using a modified progressive ratio and relapse procedure. Subjective and cardiovascular effects were also measured. Cocaine produced prototypical dose-related increases in self-administration, subjective outcomes (e.g., “Like Drug”), and cardiovascular indices (e.g., heart rate, blood pressure) during placebo maintenance. Naltrexone and bupropion alone, or in combination, did not significantly decrease self-administration on either procedure. Low doses of bupropion (i.e., 100 mg) blunted the effects of the cocaine on subjective measures of “Like Drug” and “Stimulated”. No unexpected adverse effects were observed with naltrexone and bupropion, alone and combined, in conjunction with cocaine. Together, these results do not support the use of these bupropion-naltrexone combinations for the treatment of cocaine use disorder. Future research should determine if novel drug combinations may decrease cocaine self-administration.

Original languageEnglish
Article number173526
JournalPharmacology Biochemistry and Behavior
StatePublished - Mar 2023

Bibliographical note

Funding Information:
This research was supported by grants from the National Institute on Drug Abuse ( R01DA036827 ; T32DA035200 ) of the National Institutes of Health . The funding agency 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:
© 2023


  • Bupropion
  • Cocaine
  • Naltrexone
  • Self-administration

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience


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