The neuroscience of placebo effects: connecting context, learning and health

Abstract

Placebo effects are beneficial effects that are attributable to the brain–mind responses to the context in which a treatment is delivered rather than to the specific actions of the drug. They are mediated by diverse processes — including learning, expectations and social cognition — and can influence various clinical and physiological outcomes related to health. Emerging neuroscience evidence implicates multiple brain systems and neurochemical mediators, including opioids and dopamine. We present an empirical review of the brain systems that are involved in placebo effects, focusing on placebo analgesia, and a conceptual framework linking these findings to the mind–brain processes that mediate them. This framework suggests that the neuropsychological processes that mediate placebo effects may be crucial for a wide array of therapeutic approaches, including many drugs.

The Neural Basis of Self-Touch in a Pain-Free Situation

“…The rACC plays a key role in cortical control of the brainstem during both opioid and placebo analgesia [17,18]. The brainstem opioid system consists of a network of regions, including the PAG and RVM [15,16].…”

“…In contrast, studies of pain control have shown that the ACC plays a key role in cortical control of the brainstem opioid system, which comprises the periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM) [14][15][16], during both opioid and placebo analgesia [17,18]. These neural structures constitute the descending pain modulatory system (DPMS) [19].…”

How do placebos work?

“…The recent explosion of placebo research and the shift in conceptualization of the placebo effect in several medical conditions, such as pain and motor disorders, makes us understand that their psychological and neurobiological underpinnings can be investigated in some detail. Indeed, what we have learned over the past few years is that different brain mechanisms are at work during the placebo response (Benedetti, Amanzio, Rosato, & Blanchard, 2011; Benedetti, Carlino, & Piedimonte, 2016; Wager & Atlas, 2015). …”

“…when a therapeutic ritual is performed. By using this neuroscientific approach, the placebo effect represents an excellent model to understand how the human brain works (Benedetti, 2014; Wager & Atlas, 2015) and may have profound implications for both medical practice and clinical trials (Benedetti et al, 2016). …”

“…In particular, interindividual differences in NAc-VS seem to be important for identifying placebo responders and non-responders. Indeed, strong placebo analgesic effects are predicted by NAc-VS activity, including stronger placebo-related opioid and functional magnetic resonance imaging (fMRI) activity responses during pain, increased grey matter volume, and stronger fMRI responses in a reward pursuit task unrelated to pain (Wager & Atlas, 2015). …”