# The neural bases of placebo effects and their relation to regulatory processes

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2020 · $797,673

## Abstract

Placebo treatments can induce clinically significant benefits, compared with no-treatment
controls, across a variety of disorders. But placebo treatments themselves are pharmacologically
and physically inert: Their benefits result from active brain and psychological responses to the
treatment context. Neuroscientific studies have established that placebo treatments influence
cortical-subcortical brain pathways and neurochemical systems relevant for expectation,
appraisals of personal and social meaning, and value-driven learning. These systems are also
related to symptom progression across mental health disorders and several other neurological
and substance use disorders. Understanding the brain and psychological mechanisms of placebo
effects will help improve psychological and neurological (e.g., neuromodulation-based)
treatments across disorders.
This R01 renewal funds an ongoing program of research that has made fundamental contributions
to this literature. It has also identified several significant gaps that are particularly important for
connecting placebo research to mental health. One gap is that our understanding of the brain
mechanisms underlying placebo effects comes almost purely from studies of pain. The proposed
studies extend previous work to study the brain pathways underlying placebo effects in anxiety
and social rejection, negative affective processes directly relevant for multiple mental health
disorders. Pattern-recognition (machine learning) analyses identify the most symptom-relevant
pathways, and test effects of placebo and other context interventions on these pathways. In Aim
1 (Experiments 1-3), we develop models across multiple affective symptoms, parsing affective
pathways into those that are symptom-specific and those that generalize across multiple
symptoms and outcomes. We also address the role of endogenous opioids, strongly linked to
placebo analgesia, in other negative affective experiences. Another gap is that most previous
studies of the context variables that drive strong placebo effects—including social influences,
treatment history—have not been studied extensively at the brain level. In Aim 2, we study the
brain pathways underlying several promising context interventions that enhance the strength of
placebo effects, including social modeling of successful or unsuccessful treatment response,
initial experiences of treatment success or failure, and the match between placebo suggestions
and a person’s predisposition to be receptive to them.

## Key facts

- **NIH application ID:** 9842001
- **Project number:** 5R01MH076136-13
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** TOR D. WAGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $797,673
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842001

## Citation

> US National Institutes of Health, RePORTER application 9842001, The neural bases of placebo effects and their relation to regulatory processes (5R01MH076136-13). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9842001. Licensed CC0.

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