Expectancy Modulation of Opioid Neurotransmission.

Expectancies are powerful modulators of cognitive and emotional experiences, as well as the neurobiological responses linked to these processes. In medicine, placebo effects are a clear example of how expectancies activate opioid neurotransmission in a treatment context, leading to the experience of analgesia and the improvement of emotional states, among other symptoms. Molecular neuroimaging techniques using positron emission tomography (PET) and the selective μ-opioid receptor tracer [C]carfentanil have significantly contributed to our understanding of the neurobiological systems involved in the formation of placebo effects. This line of research has described neural and neurotransmitter networks implicated in placebo effects and provided the technical tools to examine inter-individual differences in the function of placebo responsive mechanisms. As a consequence, the capacity to activate endogenous opioid networks during the administration of placebos has been linked to the concept of resiliency mechanisms, partially determined by genetic factors, and uncovered by the cognitive emotional integration of the expectations created by the therapeutic environment and its maintenance through learning mechanisms. This evidence has contributed to the understanding of the biological bases of the cognitive and psychological mechanisms implicated in the response to treatments, and opened up new opportunities for drug development and the enhancement of treatment responses. Further, delineation of these processes within and across diseases is critical to understand neural systems that could be enhanced to promote symptomatic improvement and modify disease progression.