Human Drug Discrimination: A Primer and Methodological Review

Drug-discrimination procedures empirically evaluate the control that internal drug states exert over behavior. They provide a highly selective method to investigate the neuropharmacological underpinnings of the interoceptive effects of drugs. Historically, drug discrimination has been one of the most widely used assays in the field of behavioral pharmacology. Drug-discrimination procedures have also been adapted for use with humans and are conceptually similar to preclinical drug-discrimination techniques in that a behavior is differentially reinforced contingent on the presence or absence of a specific interoceptive drug stimulus. This review gives some general history and background concerning the major theoretical concepts and principles of drug-discrimination research as well as its relevance to substance-use disorders. This article also provides a procedural overview and discusses key methodological issues that must be considered when designing and conducting a human drug-discrimination study. Although drug discrimination is unequivocally one of the most sophisticated and useful behavioral assays to investigate the underlying neuropharmacology of drugs in vivo, enthusiasm for its use has steadily declined in the last decade and a half. We conclude by commenting on the current state of drug-discrimination research and suggest potential avenues for future drug-discrimination research. Public Health Significance Substance-use disorders are an unrelenting public health concern. Human drug-discrimination procedures provide valuable information about the ability of drugs to exert control over behavior, the underlying neuropharmacology of drugs, and the abuse potential of drugs. In addition, these procedures provide a tool to screen novel medications for substance-use disorders. Overall, human drug-discrimination has significantly contributed to our understanding of the effects of commonly abused drugs and has helped to identify pharmacological and behavioral mechanisms that are targets for substance-use disorder intervention development.