Stress and Medication Effects on Cocaine Cue Reactivity
Condition: Cocaine Related Disorders
MeSH terms: Cocaine-Related Disorders
Intervention: Guanfacine; Modafinil; Placebo
Intervention MeSH terms: Guanfacine; Modafinil
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 109.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Cocaine Addiction; Cocaine Dependence

Summary:

      Stressful situations and cues associated with cocaine can lead to craving in cocaine
      dependent individuals. The purpose of this study is to determine whether guanfacine or
      modafinil are effective in reducing stress and cue induced craving in cocaine dependent
      individuals.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects must be able to provide informed consent and function at an intellectual level
        sufficient to allow accurate completion of all assessment instruments.

        Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) during
        the GCRC admission.

        Because of the high comorbidity of alcohol and marijuana use and cocaine dependence,
        individuals meeting dependence for alcohol and marijuana will be included. Individuals
        requiring medical detox from alcohol will be excluded.

        Subjects must consent to random assignment to stress vs. no stress and drug treatment
        conditions.

        Exclusion Criteria:

        Women who are pregnant, nursing or of childbearing potential and not practicing an
        effective means of birth control. Modafinil inhibits metabolism of steroidal contraceptives
        via CYP3A4 and can reduce the effectiveness of this type of birth control, female subjects
        must use one of the following methods of birth control: barrier methods (diaphragm or
        condoms with spermicide or both), surgical sterilization, use of an intra-uterine
        contraceptive device, or complete abstinence from sexual intercourse.

        Subjects with evidence of or a history of significant hematological, endocrine,
        cardiovascular (including but not limited to left ventricular hypertrophy (unless a
        cardiologist deems that it is not clinically significant), mitral valve prolapse, left
        bundle branch block, myocardial infarction, and angina), pulmonary, renal,
        gastrointestinal, or neurological disease including diabetes, as these conditions may
        affect HPA axis function.

        Subjects with any liver function test (LFTs) of greater than two times normal, as
        compromised liver function can interfere with HPA axis activity (Williams and Dluhy 1987)
        and may affect drug metabolism.

        Subjects with Addison's disease, Cushing's disease or other diseases of the adrenal cortex
        likely to affect HPA axis function.

        Subjects with a history of or current psychotic disorder or bipolar affective disorder as
        these may interfere with HPA function.

        Subjects with current major depressive disorder or post-traumatic stress disorder as these
        disorders are associated with characteristic changes in HPA axis function.

        Subjects receiving synthetic glucocorticoid therapy, any exogenous steroid therapy, or
        treatment with other agents that interfere with HPA axis function within one month of the
        time of testing.

        Subjects taking any psychotropic medications, opiates or opiate antagonists because these
        may affect HPA axis function.Participants taking SSRI's will be included.

        Subjects required to take medications that could adversely interact with study medications,
        including, but not limited to, azole type antifungals, cyclosporine, warfarin,
        theophylline, or carbamazepine. Any medications that induce or inhibit CYP3A4 pathways are
        excluded, as modafinil is metabolized through this enzyme system.

        Subjects with any acute illness or fever as this may affect HPA axis activity. Individuals
        who otherwise meet study criteria will be rescheduled for evaluation for participation.

        Subjects who are grossly obese (BMI > 39), as this may interfere with HPA axis function.

        Subjects who are unwilling or unable to maintain abstinence from alcohol and other drugs of
        abuse (except nicotine) prior to the stress task procedure.

        Subjects meeting DSM-IV criteria for substance dependence (other than nicotine, cocaine,
        alcohol or marijuana) within the past 60 days.