Challenge Study for Anti-Cocaine Antibodies: This grant proposes to develop human anti-cocaine antibodies and to determine their suitability for human administration. After completion of phase I studies we propose to test the ability of passive immunization with anti-cocaine antibodies to reduce or prevent the subjective effects of cocaine. Subjects: 20 male or female non-treatment seeking subjects with cocaine dependence will complete inpatient interaction study. Subjects will undergo standard laboratory, EEG, and EKG testing to ensure the absence of medical conditions which could be worsened by cocaine administration. Procedure: subjects will undergo monitored abstinence for at least 3 days to ensure clearance of plasma benzoylecgonine (BE). Subjects will be randomized to receive an IV injection of either antibody or vehicle (saline) in a between subjects design. Subjects will receive a test dose of 20 mg cocaine HCI at 1 mg/se IV to ensure that they tolerate cocaine in an experimental setting. Three days later, they will receive either saline or 10 g IV of human anti-cocaine antibodies. One hour later they will receive cocaine 40 mg paired with a double blind administration of saline, separated by 60 minutes. During and for 2 hours after cocaine or saline administration subjects will be intensively monitored using continuous pulse, blood pressure, EEG, and EKG with automatic arrhythmia detection. Main Outcome Measures: prior to and at 2 minutes, 5 minutes,10 minutes, 15 minutes and 30 minutes after each saline and cocaine administration subjects will provide verbal responses on 10 cm visual analogue scales assessing: high, stimulated, hungry, drowsy, energy, pleasant, down-depressed, crave-want cocaine and anxious. Blood will be drawn for cocaine blood level after each self-report period. Subjects will return to the hospital at 2 weeks and weeks to receive payment and to be assessed for late-occurring adverse reactions. Subjects will also be questioned about their cocaine use over the preceding interval and will provide a urine specimen for quantitative BE. Analysis: Area under the curve (calculated from prior to infusion to 30 minutes after) for each outcome variable will be calculated for each condition and compared using t tests.
Showing the most recent 10 out of 13 publications
