This project would examine whether active immunization with cocaine as a hapten is a potential pharmacotherapy for the treatment of cocaine abuse. The proposed research would examine whether immunization and subsequent development of cocaine antibodies will attenuate the effects of cocaine in humans and whether chronic administration of the dopamine uptake inhibitor, mazindol, will augment this attenuation.
The specific aims are as follows: 1. To determine whether the behavioral effects, physiological effects or pharmacokinetics of cocaine are altered by the presence of cocaine antibodies. 2. To determine whether the behavioral effects, physiological effects or pharmacokinetics of cocaine are altered by the chronic administration of mazindol in the presence of cocaine antibodies. Using a within-subjects design, subjects would undergo four experimental sessions during which intravenous cocaine or cocaine placebo will be administered both prior to, and 3 months following, immunization for cocaine antibodies. Subsequently, subjects would be induced onto a maintenance dose of mazindol and would undergo four experimental sessions once more. During each experimental session, the following measures would be assessed: (1) self-reported effects as a traditional measure of abuse liability; (2) performance effects as a measure of coordination and reaction time; (3) physiological effects as a measure of toxicity; and, (4) pharmacological effects as determined by plasma levels of cocaine and its metabolites over time as a measure of pharmacokinetic profile and/or drug interaction. It is hypothesized that these measures will provide a wide behavioral profile by which to determine the degree to which immunization alters cocaine?s effects, as well as whether mazindol will enhance the action of the antibody.
| Haney, Margaret; Gunderson, Erik W; Jiang, Huiping et al. (2010) Cocaine-specific antibodies blunt the subjective effects of smoked cocaine in humans. Biol Psychiatry 67:59-65 |
| Kosten, Thomas; Owens, S Michael (2005) Immunotherapy for the treatment of drug abuse. Pharmacol Ther 108:76-85 |
| Haney, Margaret; Kosten, Thomas R (2004) Therapeutic vaccines for substance dependence. Expert Rev Vaccines 3:11-8 |
| Kosten, Thomas R; Rosen, Marc; Bond, Julian et al. (2002) Human therapeutic cocaine vaccine: safety and immunogenicity. Vaccine 20:1196-204 |
| Kosten, Thomas R; Biegel, Diane (2002) Therapeutic vaccines for substance dependence. Expert Rev Vaccines 1:363-71 |
| Kantak, K M; Collins, S L; Bond, J et al. (2001) Time course of changes in cocaine self-administration behavior in rats during immunization with the cocaine vaccine IPC-1010. Psychopharmacology (Berl) 153:334-40 |
