DESCRIPTION: This proposal requests funding to use a laboratory model with human research subjects to test the impact of immunization on cocaine?s effects and on cocaine use. The widespread use of cocaine, its role in the spread of diseases such as AIDS, its use by pregnant women to the detriment of themselves and their offspring, as well as the multiplicity of cocaine?s other deleterious effects, makes imperative the control of this severe public health problem. Although behavioral interventions are a necessary module of any treatment intervention, and successes have been reported, the extraordinary reinforcing efficacy of cocaine increases the likelihood that behavioral interventions alone will be insufficient to adequately impact a substantial percentage of cocaine abusers. It is clear that other therapeutic approaches will have to be combined with behavioral therapy if most cocaine abusers are to be successfully treated. This protocol would test the hypothesis that immunization followed by adequate antibody titers will result in changes in response to cocaine such that the likelihood of cocaine use will decrease substantially. Specifically, two studies would be executed: (1) The first would compare the subjective and physiological response of research subjects to intravenous doses of cocaine before and after immunization. (2) The second would evaluate, within the context of a cocaine choice/self-administration protocol, the effects of immunization on cocaine craving, on the choice to take cocaine, and on cocaine?s other subjective and physiological effects. Specifically, the following questions are posed: 1) Are there changes in cocaine?s physiological and subjective effects (including measures of cocaine craving) measured after single doses of cocaine that are the result of immunization? Non-treatment-seeking cocaine-using volunteers will be tested before and after immunization when antibody titers are considered sufficient. Cocaine dose-response functions will be collected and blood levels of cocaine and its metabolites would be monitored under both conditions. 2) Does immunization, with sufficient antibody titers, result in reduced cocaine use? The PL?s cocaine self-administration/choice procedure is one in which non-treatment-seeking cocaine-using volunteers are given the opportunity to take repeated doses of cocaine under carefully controlled conditions before and after immunization. Measures would also be made of cocaine?s physiological and subjective effects and volunteers would have the opportunity to self-administer cocaine in doses and patterns seen in the natural ecology. The opportunity for a ?mini-binge? would be used to make it possible to generalize from these data to cocaine users outside of the laboratory and to provide support for taking this therapy to a large-scale clinical trial.