ABSTRACT
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.
Subject(s)
Cocaine/antagonists & inhibitors , Cocaine/pharmacology , Metyrapone/pharmacology , Adolescent , Adrenocorticotropic Hormone/blood , Adult , Blood Pressure/drug effects , Cocaine/blood , Cross-Over Studies , Double-Blind Method , Drug Interactions , Electrocardiography/drug effects , Female , Heart Rate/drug effects , Humans , Hydrocortisone/blood , Male , Metyrapone/adverse effects , Middle AgedABSTRACT
This article presents an overview of the definition and measurement of "craving" as it is applied to drug and alcohol abuse research. Examples of craving measures are described and organized in terms of whether they structure craving as a single factor or as a multifactorial construct. The application of craving scales in cue-conditioning studies, in medication treatment trials, and as outcome measures in other treatment studies is considered. It is concluded that no single craving scale, or type of scale, has unequivocal support, because few studies have administered more than one scale to the same population. It is suggested that our understanding of craving will be advanced by designing studies that compare and contrast several craving scales within the same study. Likewise, craving is only one possible cause of relapse. Future studies should compare several alternate relapse mechanisms within the same study.
