We have begun a program of research to develop a laboratory model of cocaine abuse using very low doses of oral cocaine, doses that produce measurable behavioral effects but minimal cardiovascular effects. The first protocol in this research program uses a drug discrimination procedure to explore the limits of human behavioral sensitivity to oral cocaine. Initially, subjects in this protocol are taught to distinguish 50 mg of oral cocaine from placebo using a drug discrimination procedure. Then subjects are exposed to 4 doses of oral cocaine (6.25 mg, 12.5 mg, 25 mg, and 50 mg) and placebo in random order across days to determine the lowest doses of cocaine that subjects can detect. Throughout all of these administrations the cardiovascular and self-reported mood effects of these cocaine doses are determined. The protocol is currently ongoing. Further studies are planned to study cocaine and opioid drug discrimination, cocaine and opioid self-administration studies, the pharmacodynamic and pharmacokinetic effects of coca tea, and a multiple-choice behavioral paradigm for screen medications.