Social Modeling Interventions for Enhancing Placebo Effect

Overseen By Tor D Wager, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Trustees of Dartmouth College

Must not be taking: Antidepressants, Mood stabilizers, Opiates, others

Disqualifiers: Psychiatric disorder, Cancer, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how social experiences and personal success or failure affect the placebo effect, which is the brain’s response to a treatment without active ingredients. Researchers aim to understand how observing others' responses to treatments and personal experiences of success or failure can influence pain relief and reactions to unpleasant images. Participants will join different groups to observe and experience these scenarios, aiding in understanding the power of expectation and context on healing. The trial seeks individuals with no current pain or serious mental health issues, who are comfortable speaking English and can undergo an MRI scan. As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research on the psychological aspects of healing.

Do I need to stop taking my current medications for the trial?

The trial requires that you have not taken antidepressants, mood stabilizers, glucocorticoids, or opiates in the last month. If you are currently on these medications, you may need to stop taking them before participating.

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

Previous studies have shown that placebos are safe, with no serious side effects reported. For example, research found no serious adverse events linked to placebo treatments. Clinical trials often use the placebo effect to assess how belief in a treatment can affect results. Studies show that placebo responses can improve symptoms like pain and anxiety, indicating that the placebo effect is generally well-tolerated. This trial focuses on how social influences and past experiences affect the placebo effect, rather than introducing new medications or chemicals. Therefore, participants can expect a low-risk experience. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how social modeling can amplify the placebo effect, potentially leading to new pain management strategies. Unlike conventional treatments that rely on medications, this approach examines how observing others' responses to placebos can influence a person's own perception of pain. This could open up new avenues for non-drug pain relief, reducing the need for pharmaceuticals and their associated side effects. The trial aims to deepen our understanding of the mind's power in pain perception, which could revolutionize how we approach treatment for various conditions.

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

Research has shown that the placebo effect can lead to real health improvements, particularly for conditions like pain and anxiety. This trial divides participants into different groups to study the impact of social modeling on the placebo effect. In the "Observed Success - Experienced Success" group, participants see others benefiting and also have their own positive experiences, often resulting in the most benefits. In the "Observed Failure - Experienced Success" group, participants succeed personally but see others not benefiting; personal success still provides some pain relief. In the "Observed Success - Experienced Failure" group, participants see others improve but don't experience it themselves; seeing others get better might still help. Lastly, in the "Observed Failure - Experienced Failure" group, where neither personal nor observed experiences are positive, participants usually see the least benefit. Overall, observing others and personal experiences can strongly influence how effective a placebo feels. ^{2 3 6 7 8}

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 English-speaking individuals without psychiatric/neurological disorders, substance abuse history, or pathological pain. They must be able to perform tasks and undergo fMRI scans, not have metal implants, and abstain from alcohol/substances before the study.

Inclusion Criteria

I can read and cooperate with an fMRI exam.

No reported substance abuse within the last six months

I am a fluent or native English speaker.

Exclusion Criteria

I have metal in my body or have worked with metal fragments.

You were born with a brain condition like cerebral palsy.

I have a neuroendocrine disorder like Cushing's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Observation

Participants watch a video of another participant undergoing the baseline assessment and placebo test procedure

1 session

1 visit (in-person)

Conditioning

Participants undergo a conditioning phase experiencing high-intensity heat before placebo treatment and then either low-intensity heat after application of a placebo cream

1 session

1 visit (in-person)

fMRI Test

Participants experience painful heat and aversive IAPS images during fMRI, on skin sites treated with Control and Placebo creams

1 session

1 visit (in-person)

Follow-up

A 3-month follow-up fMRI test phase to assess durability of brain and behavioral placebo effects

3 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Experienced Failure
• Experienced Success
• Observed Failure
• Observed Success

Trial Overview The study examines how social modeling (observing treatment outcomes in others) and personal treatment experiences affect placebo effects on pain relief. Participants are divided into four groups to observe these effects using behavioral tests and fMRI scans over three months.

How Is the Trial Designed?

Group I: Observed Success - Experienced Success Experimental Treatment 2 Interventions

This participant group (N=30) will witness a successful placebo during the "observation phase" (i.e. the demonstrator will display reduced pain expressions after receiving the cream) and experience a successful placebo during the "experience phase" (i.e. the experimenter will reduce the intensity of the pain stimuli after applying the cream).

Group II: Observed Success - Experienced Failure Experimental Treatment 2 Interventions

This participant group (N=30) will witness a successful placebo during the "observation phase" (i.e. the demonstrator will not display reduced pain expressions after receiving the cream) and experience a failed placebo during the "experience phase" (i.e. the experimenter will not reduce the intensity of the pain stimuli after applying the cream).

Group III: Observed Failure - Experienced Success Experimental Treatment 2 Interventions

This participant group (N=30) will witness a successful placebo during the "observation phase" (i.e. the demonstrator will display reduced pain expressions after receiving the cream) and experience a successful placebo during the "experience phase" (i.e. the experimenter will reduce the intensity of the pain stimuli after applying the cream).

Group IV: Observed Failure - Experienced Failure Experimental Treatment 2 Interventions

This participant group (N=30) will witness a failed placebo during the "observation phase" (i.e. the demonstrator will not display reduced pain expressions after receiving the cream) and experience a failed placebo during the "experience phase" (i.e. the experimenter will not reduce the intensity of the pain stimuli after applying the cream).

Who Is Running the Clinical Trial?

Trustees of Dartmouth College

Lead Sponsor

Trials

32

Recruited

14,500+

Published Research Related to This Trial

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 review of 27 randomized controlled trials found that brief psychological interventions can influence how patients report side effects from active medications, suggesting that managing expectations may help reduce perceived side effects.

The most effective strategy identified was omitting side-effect information, while other techniques like distraction and altering branding perceptions showed inconsistent results, indicating a need for further research to refine these interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influencing Side-Effects to Medicinal Treatments: A Systematic Review of Brief Psychological Interventions. Webster, RK., Rubin, GJ.[2020]

The placebo effect is linked to the brain's dopaminergic reward systems and is influenced by patients' expectations of treatment benefits, suggesting a biological basis for this phenomenon.

Evidence indicates that the placebo effect can be observed in various conditions, including Parkinson's disease, depression, and pain, highlighting its potential role in treatment strategies, even in long-term addiction recovery programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in neurological disorders. de la Fuente-Fernández, R., Schulzer, M., Stoessl, AJ.[2022]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0074774220300684

Statistical methods in handling placebo effect ... failed Phase 3 trials. A common cited reason for these failures is a high placebo response rate that thereby reduces the observed treatment effect.

2. health.harvard.edu health.harvard.edu/newsletter_article/the-power-of-the-placebo-effect

The power of the placebo effect For years, a placebo effect was considered a sign of failure. A placebo is used in clinical trials to test the effectiveness of treatments and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10721911/

Interpreting clinical trial outcomes complicated by placebo ... The results of this analysis indicated an enhanced signal of drug response in a failed trial and confirmed the absence of drug effect in a ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0924977X98000509

The failure of placebo-controlled studies The exclusion of eccentric centres that fail to reach predetermined performance criteria, such as a failure to separate reference treatment from placebo, may be ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32960658/

The relation between the placebo response, observed ... The relation between the placebo response, observed treatment effect, and failure to meet primary endpoint: A systematic review of clinical ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8719632/

What can be done to control the placebo response in ... placebo in the primary analysis cohort, and 1 failed to ... Error bars represent standard error of the mean (SEM) Data extracted from Treister et al.

7. journals.sagepub.com journals.sagepub.com/doi/10.1177/0333102420960020

A systematic review of clinical trials of preventative ... The relation between the placebo response, observed treatment effect, and failure to meet primary endpoint: A systematic review of clinical ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11513809/

Clinical pain management: Current practice and recent ... Patients with chronic pain frequently experience mental health problems. The ... Currently, a “trial and error” approach remains typical in clinical ...