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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the body's natural pain-relief system might reduce feelings of social pain, such as heartbreak, using naloxone, an opioid receptor blocker. Participants will receive nasal sprays containing either naloxone or a saline solution and will experience mild pain while researchers monitor their brain activity. This study suits individuals who have recently experienced an unwanted breakup and do not have major health issues, such as ongoing pain or substance abuse. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking insights.

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.

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

Research has shown that naloxone is generally safe for people and is often used in emergencies to reverse opioid overdoses. Studies have found that naloxone can cause side effects such as sweating, a runny nose, nervousness, or shivering, usually related to opioid withdrawal.

The FDA has approved naloxone for treating opioid overdoses, indicating it is usually well-tolerated. However, as this study is in its early stages, new findings about its use in this specific situation may emerge. Participants should ask questions and discuss any concerns with the research team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they are exploring how the body's own opioid system might influence the placebo effect in pain management. Unlike traditional pain treatments that directly target pain pathways, this approach involves using naloxone and saline to understand how blocking or mimicking opioid effects can alter the perception of pain through a placebo. By examining the body's natural response system with these innovative methods, scientists hope to uncover new strategies for pain relief that could complement or enhance existing options like opioids, NSAIDs, or acetaminophen, potentially leading to more effective and less addictive pain management solutions.

What evidence suggests that this trial's treatments could be effective for social pain?

Research shows that naloxone, a drug that blocks opioids, can affect pain perception. In this trial, participants will be divided into groups to receive either a saline or naloxone nasal spray. Studies have found that placebos can help reduce pain, but naloxone can undo this effect. Naloxone might stop the placebo effect by blocking the body's natural painkillers. Additionally, when administered as a nasal spray, naloxone quickly reaches the brain, potentially altering pain experience. While naloxone is commonly used to treat opioid overdoses, its effects on emotional pain and the placebo effect remain under investigation. ^{4 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 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.

Passed fMRI safety screener

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/6646208/

Placebo and naloxone can alter post-surgical pain by ... Placebo reduces post-surgical pain in comparison with no treatment, and this analgesia is apparently reversed by the opioid antagonist, naloxone. However, these ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04650841

The Role of the Opioid System in Placebo Effects on Pain ... The current study probes the involvement of the opioid system in placebo effects on social pain, using the opioid antagonist naloxone.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6785104/

Intranasal naloxone rapidly occupies brain mu-opioid ... This study provides initial characterization of brain MOR availability at high temporal resolution following intranasal (IN) naloxone administration to healthy ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2755306

Effect of Intranasal vs Intramuscular Naloxone on Opioid ... This trial found that the same dose of naloxone given intranasally was not as effective as naloxone given intramuscularly in reversing opioid overdose.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00716807

Study Details | NCT00716807 | Efficacy of Nalbuphine and ... The aim of the study is to compare the pain killing effectiveness of nalbuphine, a narcotic pain killer, administered with either placebo or naloxone, a drug ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2015/208411lbl.pdf

NARCAN (naloxone hydrochloride) nasal spray NARCAN Nasal Spray is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system ...

7. nida.nih.gov nida.nih.gov/publications/drugfacts/naloxone

Naloxone DrugFacts | National Institute on Drug Abuse Naloxone can quickly restore normal breathing to a person if their breathing has slowed or stopped because of an opioid overdose. But, naloxone ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/naloxone-nasal-route/description/drg-20165181

Naloxone (nasal route) - Side effects & dosage Naloxone nasal spray is used for emergency treatment of an opioid overdose or a possible overdose. It will temporarily reverse the effects of an opioid ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMvcm2020745

Intranasal Naloxone Administration The administration of naloxone can precipitate symptoms of opioid withdrawal, including diaphoresis, a runny nose, nervousness, and shivering or ...