  Despite growing scientific interest in the placebo effect and increasing
understanding of neurobiological mechanisms, theoretical modeling of the
placebo response remains poorly developed. The most extensively accepted
theories are expectation and conditioning, involving both conscious and
unconscious information processing. However, it is not completely understood
how these mechanisms can shape the placebo response. We focus here on neural
processes which can account for key properties of the response to substance
intake. It is shown that placebo response can be conceptualized as a reaction
of a distributed neural system within the central nervous system. Such a
reaction represents an integrated component of the response to open substance
administration (or to substance intake) and is updated through "unconditioned
stimulus (UCS) revaluation" learning. The analysis leads to a theorem, which
proves the existence of two distinct quantities coded within the brain, these
are the expected or prediction outcome and the reactive response. We show that
the reactive response is updated automatically by implicit revaluation lerning,
while the expected outcome can also be modulated through conscious information
processing. Conceptualizing the response to substance intake in terms of UCS
revaluation learning leads to the theoretical formulation of a potential
neuropharmacological treatment for increasing unlimitedly the effectiveness of
a given drug.
