Placebo Effects in Healthy Individuals

Overseen By Tor D Wager, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Trustees of Dartmouth College

Disqualifiers: Chronic pain, Heat pain intolerance

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 day per session

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different placebo (inactive treatment) suggestions affect people based on their motivational style. Participants will use a cream in two sessions: one where the placebo suggestion aligns with their motivational style and another where it does not. The trial aims to understand how personal motivation influences the placebo effect, potentially improving public health treatments. Generally healthy individuals with a strong focus on either "promotion" (seeking gains) or "prevention" (avoiding losses) might be a good fit. As an unphased trial, this study offers a unique opportunity to contribute to understanding how motivation affects treatment outcomes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that placebo treatments, such as the creams used in this trial, are generally very safe. Studies have found that placebos can have positive effects without causing harm. The placebo creams in this study are not expected to cause any side effects because they contain no active ingredients.

In fact, about 70% of people believe it's acceptable for doctors to use placebos if they benefit patients, indicating significant trust in the safety of these treatments. Overall, participants in similar studies have used placebo creams without major issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different types of placebo suggestions—framed as either "prevention" or "promotion"—can influence outcomes based on individuals' motivational styles. Unlike traditional treatments that rely on active ingredients to achieve effects, this trial examines the psychological and motivational factors that contribute to the placebo effect, potentially paving the way for more personalized and effective treatment strategies. By understanding the impact of tailored placebo suggestions, researchers hope to unlock new avenues for enhancing patient outcomes without the need for conventional drugs.

What evidence suggests that this trial's placebo treatments could be effective?

Research has shown that placebo treatments can help, particularly in easing pain, due to psychological factors such as expectations and the treatment setting. In this trial, participants will experience different placebo effects through two separate placebo cream applications: one with a "prevention" suggestion and another with a "promotion" suggestion. Studies have found that the brain's reaction to the treatment environment can lead to positive effects, even without active ingredients. Placebos often alleviate physical symptoms more readily than they alter chemical processes in the body. Additionally, placebos can change perceptions of sensations like pain and itching by teaching the body to respond differently. ^{2 6 7 8 9}

Who Is on the Research Team?

Tor D Wager, PhD

Principal Investigator

Dartmouth College

Are You a Good Fit for This Trial?

This trial is for healthy individuals who have a dominant motivational style of either 'promotion' or 'prevention', determined by screening. People with chronic pain or those who can't handle heat pain on their forearm are not eligible.

Inclusion Criteria

You must be a healthy person.

Based on our screening, you either have a strong desire to achieve your goals or a strong desire to avoid negative outcomes.

Exclusion Criteria

You are unable to handle heat applied on your forearm during the experiment based on a test done at the start.

I am currently experiencing or have recently experienced chronic pain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo two sessions with placebo suggestions tailored to match or mismatch their motivational styles

1 day per session

2 visits (in-person)

Control

Participants receive a control phase where the same cream is applied with no analgesic effects

Included in treatment sessions

Follow-up

Participants are monitored for immediate responses during painful stimulation

Immediate response on the day of participation

What Are the Treatments Tested in This Trial?

Interventions

• Control cream
• Placebo cream- "prevention" suggestion
• Placebo cream- "promotion" suggestion

Trial Overview

The study tests placebo creams with suggestions that either match ('promotion') or mismatch ('prevention') participants' motivation styles, against a control cream without any suggestion to see how they affect the perception of pain.

How Is the Trial Designed?

Group I: Placebo Experimental Treatment 2 Interventions

All participants will participate in two sessions, one with a placebo suggestion that matches the participant's motivational style, and one with placebo suggestion that does not match their motivational style, in a pseudo-random order.

Group II: Control Experimental Treatment 1 Intervention

Each session will also include a control phase, in which the same cream will be applied, and participants will be instructed that the cream has no analgesic effects.

Who Is Running the Clinical Trial?

Trustees of Dartmouth College

Lead Sponsor

Trials

32

Recruited

14,500+

Published Research Related to This Trial

A systematic review of 234 randomized placebo trials involving 10,525 patients found that placebo interventions generally do not have clinically important effects across various health conditions, with a pooled effect size indicating minimal benefit.

However, placebo interventions showed some influence on patient-reported outcomes, particularly for pain and nausea, although the effects varied widely and were often difficult to separate from reporting biases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo interventions for all clinical conditions. Hróbjartsson, A., Gøtzsche, PC.[2022]

The study demonstrated that placebo responses can be conditioned in humans, meaning that people can learn to associate a placebo with either pain relief or increased pain based on prior experiences.

By manipulating nociceptive stimulation levels during the conditioning phase, the researchers showed that both positive (pain relief) and negative (pain exacerbation) placebo effects can be induced, highlighting the potential for using learning theories to understand and harness placebo effects in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditioned placebo responses. Voudouris, NJ., Peck, CL., Coleman, G.[2019]

The placebo effect can significantly relieve pain and improve affective disorders, indicating that inert medications can have real therapeutic benefits for patients.

Despite its potential, the placebo effect is often underutilized in clinical practice and inadequately assessed in clinical trials, highlighting the need for greater recognition and understanding of its mechanisms and impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A guide to the pharmacology of placebos. Gowdey, CW.[2022]

In a study of 102 healthy participants, those who received open label placebos (OLPs) with information about their benefits (OLP-plus) showed increased well-being, particularly when their baseline well-being was low, highlighting the importance of context and information in placebo effects.

The OLP-plus group had higher expectations about the treatment's effectiveness, which helped improve their physical symptoms compared to the control group, suggesting that providing rationale can enhance the efficacy of OLPs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of positive information provision in open-label placebo effects. Barnes, K., Babbage, E., Barker, J., et al.[2023]

A new checklist called TIDieR-Placebo has been developed to improve the reporting of placebo or sham interventions in clinical trials, ensuring that researchers clearly describe these components alongside active treatments.

The checklist was created through expert consultation and aims to enhance the transparency of trial results, which is crucial for accurately assessing the benefits and harms of active interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. Howick, J., Webster, RK., Rees, JL., et al.[2020]

Citations

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Placebo Effects in Healthy Individuals · Info for Participants

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Initial meta-analytic evidence suggests that OLPs delivered with such a suggestive rationale tend to be more effective than those without it.

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... Ointment for AD participants, using defined concentrations of the topical cream based on the PK and safety data in healthy volunteers in Phase I ...

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Beliefs About Pharmaceutical Medicines and Natural ...

We found that placebo analgesia was influenced by beliefs about natural remedies, pharmaceutical medicines, and about pain.

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pmc.ncbi.nlm.nih.gov

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This paper can provide a framework for conducting PCT with systemic medications for patients with AD.