Drug self-administration methods in abuse liability evaluation.

The human drug self-administration paradigm is an extension of the animal model developed in the 1960s. The paradigm can be used to investigate the determinants and correlates of drug-seeking and drug-taking behavior and has proven useful in the development of medications for treating drug dependence. This paper describes the basic components of the human self-administration model and discusses studies that illustrate some of its applications, including assessment of the reinforcing effects of drugs, analysis of behavioral and pharmacological mechanisms of drug self-administration and measurement of the abuse liability, behavioral toxicity, and aversive effects of drugs. Some of the strengths and limitations of using the paradigm with human research subjects are also presented. It is concluded that the drug self-administration model should not replace other measures of abuse liability testing in humans, but should be incorporated into comprehensive programs of drug abuse assessment wherever possible.