This double-blind, double dummy, placebo-controlled (diphenhydramine-25 mg BID) residential study assesses the psychological, physiological, cardiovascular, cognitive, electroencephalographic, and pharmacokinetic effects of the carbamazepine-cocaine interaction in cocaine-abusing subjects not currently dependent on other drugs. Eighteen subjects are randomly assigned to 4 parallel groups: (1) low plasma carbamazepine levels (1-3 mg/L), (2) placebo short-stay (6 weeks); (3) middle plasma carbamazepine levels (4-7 mg/L); and (4) placebo long-stay (9 weeks). Subjects can self-administer cocaine-25 mg IV (or blank) or receive a monetary reward up to thrice daily 3 days each week by making a stimulus-controlled operant response. On self-administration days, subjects undergo 24-hour ambulatory monitoring of cardiovascular function, and answer computer administered questions on their subjective state. Subjects' response to cocaine-associated stimuli and their EEG and cognitive function are assessed periodically. Thus, the influence of carbamazepine on cocaine reinforcement and cocaine-induced psychological and physiological effects can be assessed. Blood, saliva, and hair samples are collected periodically to assess cocaine and carbamazepine pharmacokinetics. This is the largest, most detailed study to date investigating the clinical pharmacology of the carbamazepine-cocaine interaction.
