RESEARCH ON INDIVIDUAL SENSITIVITY TO BENZODIAZEPINES

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OBJECTIVES: The broad objectives of this study are to identify anxiety disorder patients who are at risk for drug dependence by examining individual differences in BZ self-administration and to evaluate specific psychosocial, pharmacological, and biological correlates of this behavior. SPECIFIC AIMS: We will examine: 1) whether individual differences in alprazolam (Alz) sensitivity predicts self-medication behavior, 2) whether levels of 'stress hormones" such as cortisol mediate drug sensitivity and/or patterns of Alz use, and 3) whether a period of prescribed dosing influences how patients later choose to self-medicate with Alz. METHODS: 30 M,F anxiety disorder patients will participate in this 12-week outpatient study. Patients will initially be hospitalized overnight for a neuroendocrine assessment that will include 24 hr. monitoring of cortisol/ACTH blood levels and a CRH Stimulation Test. A self- administration procedure will be used to determine how individual patients would choose to use Alz to treat anxiety when they take it "as needed." Self-medication behavior will be assessed for on-week of placebo, one week of alprazolam, and one week of concurrent access to both placebo and alprazolam. Patients will be classified as either HIGH or LOW users based on their observed patterns of use. The self-medication procedure will be followed by 4 weeks of prescribed doses of medication (Alz and placebo). A different dose of Alz will be given each week to examine dose-response. Group differences in anxiolytic effects, sedative effects, psychomotor performance effects, cortisol levels, and drug liking will be evaluated. Finally, patients will complete the second self- administration procedure in which they may again self-medicate "as needed" so that we can evaluate whether p.r.n. patterns of use have changed subsequent to the prescribed dosing.