Opioid System's Role in Placebo Effects for Pain

Overseen By Tor D Wager, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Trustees of Dartmouth College

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

Disqualifiers: Psychiatric disorder, Substance abuse, Cancer, others

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

Compensation: Varies

Number of Visits: 2

Duration: 2 sessions

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The current study probes the involvement of the opioid system in placebo effects on social pain, using the opioid antagonist naloxone. 60 participants who recently experienced an unwanted breakup will experience rejection-related stimuli and receive painful heat and pressure stimuli during fMRI scanning. Participants will be randomized to receive either a naloxone or saline nasal spray, and be informed that the spray is either saline, or an effective pain and negative emotion reducing agent.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment Control Cream with Naloxone, Control Cream with Saline, Placebo Cream with Naloxone, Placebo Cream with Saline?

Research shows that placebo treatments can reduce pain, and this effect is partly due to the body's natural pain-relief system involving endorphins. Naloxone, which blocks this system, can reduce the pain-relief effect of placebos, indicating that the opioid system plays a role in placebo-induced pain relief. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The studies suggest that naloxone, when used in these trials, did not have significant effects on pain or mood, indicating it is generally safe in humans at the doses used. ^{1 2 3 6 7}

How does this treatment differ from other treatments for pain?

This treatment is unique because it explores the role of the body's own opioid system in creating placebo effects for pain relief, which is different from traditional pain treatments that directly target pain pathways with medications. The study suggests that placebo effects can be influenced by the body's natural opioids, and this effect can be altered by naloxone, an opioid blocker, highlighting a novel approach to understanding and potentially enhancing pain management. ^{1 2 3 8 9}

Research Team

Tor D Wager, PhD

Principal Investigator

Dartmouth College

Eligibility Criteria

This trial is for adults aged 18-55 who speak English and have recently gone through an unwanted breakup. They must not have psychiatric/neurological disorders, substance abuse history in the last six months, or any conditions that would interfere with MRI scanning. Participants should not be on certain medications or have metal implants due to MRI requirements.

Inclusion Criteria

I do not have ongoing or recent severe pain or neurological disorders.

I can read and cooperate with an fMRI exam.

You recently went through a tough breakup with your romantic partner.

Exclusion Criteria

I am currently experiencing pain.

You have a history of using drugs or alcohol in a way that caused problems or dependence.

You are afraid or uncomfortable in small, enclosed spaces.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either naloxone or saline nasal spray and undergo fMRI scanning while experiencing rejection-related and painful stimuli

2 sessions

2 visits (in-person)

Follow-up

Participants are monitored for intervention effects on negative affect and pain ratings immediately after stimuli

Immediately after each session

Treatment Details

Interventions

• Control Cream with Naloxone
• Control Cream with Saline
• Placebo Cream with Naloxone
• Placebo Cream with Saline

Trial Overview The study tests how a placebo cream combined with either naloxone (blocks opioid effects) or saline affects pain and feelings of social rejection after a breakup. During fMRI scans, participants will face rejection stimuli and painful sensations while being told they're receiving a treatment that could reduce pain and negative emotions.

Participant Groups

Group I: Saline Group Experimental Treatment 2 Interventions

Participants will receive saline in the nasal spray.

Group II: Naloxone Group Experimental Treatment 2 Interventions

Participants will receive 4mg naloxone nasal spray.

Who Is Running the Clinical Trial?

Trustees of Dartmouth College

Lead Sponsor

Trials

32

Recruited

14,500+

Findings from Research

In a study involving 87 healthy volunteers, providing individuals with control over when they administer a placebo treatment significantly enhanced the effectiveness and duration of placebo analgesia compared to standard passive conditioning.

Participants with instrumental control not only experienced greater pain relief but also showed reduced anxiety responses, suggesting that giving patients control could be a simple and ethical way to improve pain management outcomes in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Instrumental Control Enhances Placebo Analgesia. Tang, B., Geers, A., Barnes, K., et al.[2020]

References

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

Partial antagonism of placebo analgesia by naloxone. [2022]

2. Norway pubmed.ncbi.nlm.nih.gov

[Placebo effects and controlled clinical trials]. [2013]

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

Placebo and naloxone can alter post-surgical pain by separate mechanisms. [2019]

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

Response expectancies in placebo analgesia and their clinical relevance. [2022]

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

Instrumental Control Enhances Placebo Analgesia. [2020]

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

Endorphins: naloxone fails to alter experimental pain or mood in humans. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Do Endorphins Mediate Placebo Analgesia? A Critical Commentary on One of the Seminal Papers. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Disruption of opioid-induced placebo responses by activation of cholecystokinin type-2 receptors. [2021]

9. England pubmed.ncbi.nlm.nih.gov

The mechanism of placebo analgesia. [2022]