Stimulus functions of caffeine in humans: relation to dependence potential

The interoceptive stimulus functions common to drugs of dependence include positive subjective effects, discriminative functions, and reinforcing functions. Data from studies measuring these stimulus functions constitute the objective assessment of a drug's dependence potential. This paper reviews the subjective effects, discriminative stimulus, and reinforcing stimulus functions of caffeine in humans to assess the dependence potential of caffeine. The stimulus effects of caffeine are compared with those of d-amphetamine, a prototypic CNS stimulant that has been studied under similar conditions, to evaluate the relative dependence potential of caffeine. Finally, caffeine's effects are evaluated in terms of generally accepted criteria for defining drug dependence. It is concluded that caffeine partially meets the primary criteria of drug dependence: 1) the majority of caffeine use is highly controlled, but not compulsive; 2) caffeine is psychoactive; and 3) caffeine functions as a reinforcer under certain conditions in humans, but not in animals. Caffeine thus has limited dependence potential. Additionally, although caffeine shares stimulus functions with d-amphetamine, it does so under limited conditions and should be considered to have a relatively lower dependence potential.