The necessity and utility of abuse liability evaluations in human subjects.

Assessments of the abuse potential of psychoactive drugs in preclinical and clinical studies are used in regulatory decision making process in the United States under the Controlled Substance Act (CSA) and the Federal Food, Drug, and Cosmetic Act (FD & C Act). Two types of drugs are evaluated in abuse potential studies, those being developed for a therapeutic indication by the pharmaceutical industry and illicitly manufactured 'street drugs' of abuse. Only the former will be considered here. In the case of drugs being pursued for marketing or are amendable to study in human subjects and are of scientific, medical, or regulatory interest, preclinical data may be inadequate for drug scheduling and marketing decisions. Preclinical data assessment can suggest hypotheses which must be validated in clinical studies. Moreover, there are limitations to the feasibility of evaluating certain drugs/dosage forms in preclinical studies. Thus, clinical studies are needed for the following scientific reasons: to validate preclinical hypotheses; to assess the time-course of subjective effects as a function of dose and route of administration; to evaluate the generalizability of drug liking in different human subject populations; and to evaluate the effects of drugs on cognitive and affective processes. Clinical studies are also needed if a claim is made regarding reduced or no abuse potential; and lack of additive or potentiative effects with alcohol.