It is important to conduct a drug abuse potential study for a new drug that may have potential to be abused. The acute dose-effect comparisons of the test, positive control, and placebo treatments are often performed on healthy volunteers with histories of drug abuse in drug abuse clinical trials. Because of large between-subject variability in endpoint measurements based on self-evaluated responses and the difficulty in recruiting appropriate study subjects; the designs for such studies are typically crossover, with self-control. In this presentation, issues in those studies are discussed. Some strategies for improving existing designs are proposed.