CBT and Modafinil for Cocaine Addiction

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DESCRIPTION (provided by applicant): Thus far, an effective pharmacologic treatment for cocaine dependence has not been discovered. The present trial proposes cognitive behavior therapy (CBT) as the psychosocial platform to compare two doses of modafinil with placebo for the treatment of cocaine addiction. Modafinil is a marketed, atypical stimulant which has been approved by the FDA for the treatment of nacrolepsy. Modafinil acts intracellularly in several nuclei in the anterior hypothalamus to promote cortical activation, but does not alter dopamine systems. Controlled trials with modafinil indicate that it decreases hypersomnolence, elevates mood, enhances attention/concentration, and decreases appetite. Several preclinical human trials indicate that abuse potential of modafinil is low. Side effect profile for modafinil is modest and modafinil does not have pharmacokinetic interactions with cocaine, amphetamines, or methylphenidate. In a human laboratory study (n=12) from our group, Modafinil 400 and 800 mg suppressed subjective "high," "drug effect," and "amount willing to pay for high" to both low doses (20 mg) and high doses (40 mg) of IV cocaine. We postulate that modafinil serves as an atypical agonist replacement therapy for cocaine. Modafinil should ameliorate the symptoms of cocaine abstinence, blunt multiple dimensions of the cocaine "high" and enhance benefits of the CBT. To test these hypotheses and the safety of modafinil, we propose a two week screening baseline period followed by an eight week randomized parallel study of modafinil 200 mg, 400 mg and placebo daily. Follow up will occur four and eight weeks after all therapies cease. Outcome measures will include the number of cocaine non-use days and consecutive non-use days as assessed by self-report that will be confirmed by urine assays for quantitative benzoylecgonine three times a week. Secondary assessments will include measures of mood, daytime sleepiness, and subjective aspects of cocaine withdrawal and cocaine "high." Compliance with placebo and study medications will be assessed by quantitative urine riboflavin levels and serum modafinil levels. Safety will be assessed by a combination of self-report and repeated physical examinations, laboratory studies, ECGs, and monitoring by an independent data safety monitoring board.