Effects of the combination of metyrapone and oxazepam on cocaine craving and cocaine taking: a double-blind, randomized, placebo-controlled pilot study

J Psychopharmacol. 2012 Jul;26(7):973-81. doi: 10.1177/0269881111430745. Epub 2012 Jan 11.


Although cocaine dependence affects an estimated 1.6 million people in the USA, there are currently no medications approved for the treatment of this disorder. Experiments performed in animal models have demonstrated that inhibitors of the stress response effectively reduce intravenous cocaine self-administration. This exploratory, double-blind, placebo-controlled study was designed to assess the safety and efficacy of combinations of the cortisol synthesis inhibitor metyrapone, and the benzodiazepine oxazepam, in 45 cocaine-dependent individuals. The subjects were randomized to a total daily dose of 500 mg metyrapone/20 mg oxazepam (low dose), a total daily dose of 1500 mg metyrapone/20 mg oxazepam (high dose), or placebo for 6 weeks of treatment. The outcome measures were a reduction in cocaine craving and associated cocaine use as determined by quantitative measurements of the cocaine metabolite benzoylecgonine (BE) in urine at all visits. Of the randomized subjects, 49% completed the study. The combination of metyrapone and oxazepam was well tolerated and tended to reduce cocaine craving and cocaine use, with significant reductions at several time points when controlling for baseline scores. These data suggest that further assessments of the ability of the metyrapone and oxazepam combination to support cocaine abstinence in cocaine-dependent subjects are warranted.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cocaine / analogs & derivatives
  • Cocaine / urine
  • Cocaine-Related Disorders / drug therapy*
  • Cocaine-Related Disorders / prevention & control
  • Cocaine-Related Disorders / urine
  • Diagnostic and Statistical Manual of Mental Disorders
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination / adverse effects
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • GABA Agonists / administration & dosage
  • GABA Agonists / adverse effects
  • GABA Agonists / therapeutic use*
  • Humans
  • Louisiana
  • Male
  • Metyrapone / administration & dosage
  • Metyrapone / adverse effects
  • Metyrapone / therapeutic use*
  • Middle Aged
  • Oxazepam / administration & dosage
  • Oxazepam / adverse effects
  • Oxazepam / therapeutic use*
  • Patient Compliance
  • Patient Dropouts
  • Pilot Projects
  • Secondary Prevention
  • Steroid 11-beta-Hydroxylase / administration & dosage
  • Steroid 11-beta-Hydroxylase / adverse effects
  • Steroid 11-beta-Hydroxylase / antagonists & inhibitors*
  • Substance Withdrawal Syndrome / prevention & control*


  • Enzyme Inhibitors
  • GABA Agonists
  • benzoylecgonine
  • Oxazepam
  • Steroid 11-beta-Hydroxylase
  • Cocaine
  • Metyrapone