Naltrexone/bupropion for obesity: an investigational combination pharmacotherapy for weight loss

Pharmacol Res. 2014 Jun:84:1-11. doi: 10.1016/j.phrs.2014.04.004. Epub 2014 Apr 19.


The mechanism of action of the combination therapy, naltrexone/bupropion (NB), for obesity has not been fully described to date. Weight loss attempts rarely result in long-term success. This is likely a result of complex interactions among multiple peripheral and CNS systems that defend against weight loss, and may explain the overwhelming lack of effective obesity treatments. NB is an investigational combination therapy for obesity that was developed based on evidence that obesity involves alterations in the hypothalamic melanocortin system as well as brain reward systems that influence food craving and mood. Naltrexone and bupropion both have actions in these brain regions that may cause them to influence food intake, food craving, and other aspects of eating behavior that affect body weight. We review the individual actions of naltrexone and bupropion in brain hypothalamic and reward systems, and describe the current in vitro, in vivo, and clinical evidence for how NB influences food intake and produces weight loss.

Keywords: Bupropion; Drug interactions; Food craving; Food intake; Hypothalamus; Naltrexone; Obesity; Reward system; Weight loss.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents, Second-Generation / pharmacology
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Bupropion / pharmacology
  • Bupropion / therapeutic use*
  • Drug Therapy, Combination
  • Energy Metabolism / drug effects
  • Humans
  • Naltrexone / pharmacology
  • Naltrexone / therapeutic use*
  • Narcotic Antagonists / pharmacology
  • Narcotic Antagonists / therapeutic use*
  • Obesity / drug therapy*
  • Weight Loss / drug effects*


  • Antidepressive Agents, Second-Generation
  • Narcotic Antagonists
  • Bupropion
  • Naltrexone