Metyrapone and cocaine: a double-blind, placebo-controlled drug interaction study

Pre-clinical research suggests that suppression of adrenocorticosteroid synthesis might decrease susceptibility to stress-induced relapse. Metyrapone effectively suppresses cortisol synthesis and thus might have promise as a cocaine dependence treatment. The present inpatient study evaluated the interaction of metyrapone and cocaine to assess the safety of conducting an outpatient trial. Twelve nontreatment-seeking cocaine-dependent individuals completed this double-blind, placebo-controlled, crossover study with two factors: medication (750 mg of metyrapone vs. placebo) and infusion (40 mg of cocaine vs. saline). Safety measures included vital signs, adverse events, and electrocardiogram. Efficacy measures included visual analog scale (VAS) ratings of craving and drug effect. Neuroendocrine measures included cortisol and ACTH. As predicted, metyrapone was well tolerated and did not exacerbate cocaine's physiological effects. Also as predicted, metyrapone did not significantly alter cocaine's subjective effects. The results of the present study suggest that metyrapone at the dose studied can likely be used safely in an outpatient study with active cocaine users.