Abstract
The placebo effect is widely recognized but important questions remain, for example whether the capacity to respond to a placebo is an evolved, and potentially ubiquitous trait, or an unpredictable side effect of another evolved process. Understanding this will determine the degree to which the physiology underlying placebo effects might be manipulated or harnessed to optimize medical treatments. We argue that placebo effects are cases of phenotypic plasticity where once predictable cues are now unpredictable. Importantly, this explains why placebo-like effects are observed in less complex organisms such as worms and flies. Further, this indicates that such species present significant opportunities to test hypotheses that would be ethically or pragmatically impossible in humans. This paradigm also suggests that data informative of human placebo effects pre-exist in studies of model organisms.