Preclinical studies have linked corticosteroids and animal models of drug addiction. The proposed experiments will provide a better understanding of the contribution of cortisol to methamphetamine addiction in human drug users. Subjects will be methamphetamine users experienced in the use of the drug, without a history of serious adverse effects, and familiar with the effects of the drugs. Experienced users would likely represent sensitized users, making it possible to study the role of corticosteroids in the maintenance of addiction, relevant to the target population of dependent users. Subjective, physiological, and endocrine responses to augmenting cortisol level with hydrocortisone and to lowering cortisol level with the corticosteroid synthesis inhibitor metyrapone will be studied. If lowering cortisol levels reduces the reinforcing effects of methamphetamine, antiglucocorticoid treatment could prove to be an important component of stimulant abuse treatment. The services provided by the GCRC are vital to the successful completion of this study. To ensure subject compliance and safety, we will require inpatient hospitalization from the day before dosing through 48 hours postdosing for each of six separate admissions. Some of the services we will need from the GCRC include clinical admitting procedures, placement of IV catheters, monitoring vital signs at specified times, collecting, processing and packaging study-mandated urine and blood samples.
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