Marta Peciña Iturbe, MD, PhD
Research Assistant Professor
Department of Psychiatry and Depression Center, University of Michigan
Talk title: Molecular and Functional Mechanisms of Placebo Effects: Towards the Validation of Biomarkers in Clinical Trials.
Abstract: Endogenous opioid and non-opioid mechanisms [e.g. dopamine (DA), endocannabinoids (eCB)] have been implicated in the formation of placebo effects, with initial reports dating back three-decades. Besides the perspective that placebo effects confound randomized clinical trials (RCTs), the information so far acquired points to neurobiological systems that when activated by positive expectations and maintained through conditioning and reward learning are capable of inducing physiological changes that lead to the experience of analgesia and improvements in emotional state. Functional and molecular neuroimaging techniques with positron emission tomography (PET) and the selective μ-opioid and D2/D3 radiotracers [11C]carfentanil and [11C]raclopride 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 responses and provided the technical tools to examine inter-individual differences in the function of placebo responsive mechanisms, and potential surrogate markers. As a consequence, the formation of biological placebo effects is now being 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. Further work needs to extend this research into clinical conditions where the rates of placebo responses are high and its neurobiological mechanisms have been largely unexplored (e.g. mood and anxiety disorders, persistent pain syndromes, or even Parkinson Disease and multiple sclerosis). Moreover, current progress in our understanding of the biological bases of placebo effects should be use to inform future clinical trial designs as well as potential biological targets that have not been contemplated in traditional drug development.
Co-Sponsored by the Program in Placebo Studies/BIDMC/HMS