Assessment of dependence potential of drugs in humans using multiple indices.

The study was designed to determine whether behavioral effects of amphetamine, which have been used to predict dependence potential, were stable after multiple exposures to the drug and whether these different indices of dependence potential were correlated. Ten normal human volunteers participated in a series of three identical choice experiments comparing 10 mg d-amphetamine and placebo. Each experiment consisted of nine sessions. During the first four sessions of each experiment, subjects alternately received amphetamine or placebo. During the next five sessions of each experiment, they were given a choice between amphetamine and placebo. Subjective effects were assessed using the Profile of Mood States (POMS) before drug was taken and 1, 3, and 6 h later. Liking scores were obtained after each session, as well as after each experiment. Subjects chose amphetamine an average of 3.9, 3.0, and 3.4 times out of five in the three experiments, in that order. Compared to placebo, amphetamine produced changes in mood as measured by the POMS including increased anxiety, vigor, friendliness, elation, arousal, and positive mood, and decreased fatigue. Liking scores for amphetamine were consistently higher than for placebo. Mood changes and liking scores produced by amphetamine were similar across all three experiments and across subjects. These results indicate that neither tolerance or increased sensitivity develops to the reinforcing properties of 10 mg d-amphetamine. The results are also discussed in terms of methods for predicting the dependence potential of psychotropic drugs and understanding the role of environmental context as a modulator of a drug's reinforcing effects.