Typically, the effects of a drug, and alterations in these effects over the course of repeated administrations (i.e., tolerance and sensitization), have been attributed to wholly systemic mechanisms. For example, the effect of an exogenous opiate may be attributable to its effects at central endorphin receptors, and tolerance may be the result of the neurochemical alterations induced by repeated drug administrations. It has become apparent, however, that drug effects are importantly modulated by nonpharmacological factors. The result of the chemical stimulation depends not only on pharmacodynamic and pharmacokinetic principles, but also upon the recipient’s previous experiences and expectations.