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K.D. Janda
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Drug Addiction & Abuse: Immunopharmacotherapy
Drug Addiction & Abuse: Immunopharmacotherapy
Drug addiction is a major worldwide medical and social problem that continues to escalate. The addiction syndrome is remarkably similar between different drugs of abuse and can be characterized as a chronic relapsing brain disorder with neurobiological changes that lead to compulsion to take a drug with loss of control over drug intake. In essence, the subjective effects of drug taking are euphoric and stimulating, and absence of the drug results in dysphoria and depression. Although drug dependence and transition from "use" to "abuse" is ultimately complex, involving the interplay both of positive reinforcement, and negative reinforcement/withdrawal phenomena, interestingly, the substances most sought and abused constitute a small subset of naturally occurring compounds and some related synthetic derivatives. In particular, the effects derived from cocaine, nicotine, amphetamines, and opiates trigger mechanisms in the brain as primitive and fundamental as those activated by food, water, and sex. Hence, although complete eradication of drug addiction in society may be an ideal, therapeutic interventions to alleviate addiction problems will nonetheless have an enormous impact on improving the quality of our lives. Presently used medications for the treatment of dependence disorders are based on drugs that are either agonists or antagonists of drugs of abuse, and have yielded only limited success. Immunopharmacotherapy is based on the generation or administration of antibodies that are capable of binding the targeted drug before it can reach the brain.

There is increasing evidence suggesting that immunopharmacotherapy offers a potentially useful approach to combat drug addiction. Over the past decade, we have examined the ability to treat addiction to a number of drugs using an immunopharmacotherpeutic approach, including cocaine, nicotine, tetrahydrocannabinol (THC) and rohypnol. Our results have clearly demonstrated that many of the psychological and physical effects resulting from drug exposure can be alleviated through either active vaccination (i.e., immunization with a hapten-protein conjugate) or passive immunization (i.e., direct delivery of a monoclonal antibody designed to bind the drug in question). We continue to be very active in this field and our research in this area spans chemistry, molecular biology, immunology, and behavioral pharmacology. Current targets include optimization of antibody binding by X-ray structure-directed mutagenesis, enhancement of catalytic rates by high-throughput screening of phage-displayed antibody libraries, synthesis of novel drug-like haptens designed to yield significantly increased antibody titers, and, in collaboration with Prof. George Koob (TSRI), testing of active and passive vaccination strategies in animal models.