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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study examines the effects of placebo suggestions tailored to match or mismatch individual participants' motivational styles-an issue of person-situation 'fit' with important effects in public health settings, but which has been ignored in past research.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment Control cream, Placebo cream- 'prevention' suggestion, Placebo cream- 'promotion' suggestion?

Research suggests that placebo treatments can have beneficial effects, especially in reducing pain, due to psychological factors like expectation and conditioning. This means that even if a cream doesn't contain active ingredients, the belief that it will work can lead to real improvements in how people feel. ^{1 2 3 4 5}

Is the placebo cream safe for use in humans?

In clinical trials, placebos are generally considered safe, but some participants may experience side effects due to the nocebo effect, where negative expectations can cause adverse reactions. In a study of depression trials, 44.7% of placebo-treated patients reported at least one adverse event, and 4.5% discontinued due to intolerance. ^{3 6 7 8 9}

How does the placebo cream treatment differ from other treatments?

This treatment is unique because it explores the psychological impact of suggestion on placebo effects, using creams with different 'prevention' and 'promotion' suggestions to influence outcomes. Unlike standard treatments, it focuses on how expectations and conditioning can alter perceived effectiveness, rather than relying on active ingredients. ^{1 3 4 10 11}

Research Team

Tor D Wager, PhD

Principal Investigator

Dartmouth College

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Conditioned placebo responses. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Placebo interventions for all clinical conditions. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The role of positive information provision in open-label placebo effects. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

[Clinical significance of the placebo effect]. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

Nocebo in clinical trials for depression: a meta-analysis. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Nocebo effects and participant information leaflets: evaluating information provided on adverse effects in UK clinical trials. [2021]

9. Ireland pubmed.ncbi.nlm.nih.gov

Explaining all without causing unnecessary harm: Is there scope for positively framing medical risk information? [2019]

10. United States pubmed.ncbi.nlm.nih.gov

A conditioned response model of the placebo effect predictions from the model. [2019]

11. Canada pubmed.ncbi.nlm.nih.gov

A guide to the pharmacology of placebos. [2022]