Effect of rapamycin on cue-induced drug craving in abstinent heroin addicts

Eur J Pharmacol. 2009 Aug 1;615(1-3):108-12. doi: 10.1016/j.ejphar.2009.05.011. Epub 2009 May 23.


The mammalian target of rapamycin is an evolutionarily conserved serine-threonine kinase (mTOR), which controls protein synthesis and catabolism in response to environmental cues. This randomized double-blind clinical trial enrolled 60 abstinent heroin addicts and randomly assigned them to three groups: placebo, 2.5 mg and 5 mg rapamycin. The participants were given the cue-reactivity paradigm with 5 min exposures to neutral and drug-related imagery while craving, anxiety, blood pressure and heart rate pre- and post-exposure were assessed. We found that drug-related cues increased both craving and anxiety of abstinent heroin addicts, and had no effect on blood pressure and heart rate. A single high-dose of rapamycin significantly reduced the craving, but not anxiety induced by drug-related cues. Our findings suggested that rapamycin merits outpatient clinical trials as a potential pharmacotherapy for relapse prevention from drug-related cue induced craving.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety / drug therapy
  • Anxiety / psychology
  • Blood Pressure / drug effects
  • Cues*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Heart Rate / drug effects
  • Heroin Dependence / drug therapy*
  • Heroin Dependence / physiopathology
  • Heroin Dependence / psychology*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use*
  • Substance Withdrawal Syndrome / drug therapy
  • Substance Withdrawal Syndrome / physiopathology
  • Substance Withdrawal Syndrome / psychology


  • Immunosuppressive Agents
  • Sirolimus