DESCRIPTION: (Applicant's Abstract) Cocaine abuse is among the most pressing health and sociological problems confronting developed nations the world over. In the U.S., thousands of new users are added each and each year a large proportion die from overdose of other toxic influences. The effects on the unborn can be especially tragic. Those addicted to cocaine represent the financial and social deterioration that this drug can inflict. Significantly, abuse is detrimental not only to the well-being of the individual, but also escalates to degrade the infrastructure of society. Of particular concern is the link between intravenous cocaine administration and the spread of AIDS. The biochemistry of the action of cocaine is complex having perhaps the most unique and powerful reinforcing properties of any drug. While a number of pharmaceuticals have been evaluated, none have proven to be truly effective. Hence, there remains no concrete medical solution to the cocaine problem and it has become obvious that alternative avenues must be explored. One such approach invokes immunological strategies for the direct treatment of cocaine abuse and addiction in preventative or rehabilitative contexts. In this way, social programs would be bolstered by an objective scientific foundation. This proposal specifically delineates aspects of the chemistry, immunochemistry, and immunology necessary for the implementation of immunopharmacological protocols in the abatement of cocaine abuse. The program encompasses synthesis of haptens and reagents, monoclonal antibodies (mAbs) that bind cocaine with high affinity and specificity, catalytic mAbs that degrade cocaine, development of noncatalytic and catalytic vaccine designs, human anti-cocaine mAbs derived from combinatorial libraries, and sophisticated animal behavioral paradigms for testing all therapies. Details of preliminary results and future directions are provided.