The Role of the Opioid System in Placebo Effects on Pain and Social Rejection

NCT04650841 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 230136
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pain; Rejection; Placebo Effect

Outcome Measures

Primary Outcomes (6)

• Intervention effects on pain ratings

  Pain ratings will be given on a 0-100 scale. 0 being "no pain at all" and 100 being "most pain imaginable in the context of this study."

  Immediately after pain stimuli

• Intervention effects on negative affect ratings

  Rejection ratings will be given on a 0-100 scale. 0 being "not rejected at all" and 100 being "very rejected."

  Immediately after rejection stimuli

• Brain: Pain signature response

  A priori regions of interest response from the brain (fMRI) patterns to the pain.

  Immediately after pain stimuli

• Brain: Rejection signature response

  A priori regions of interest response from the brain (fMRI) patterns to rejection. The investigators will utilize a multivariate brain pattern developed and published in Woo et al., 2014, Nature Communications. This is a rejection-selected pattern of brain activity.

  Immediately after rejection stimuli

• Skin conductance

  Skin conductance response (SCR) will be recorded during the task.

  Immediately after pain/rejection stimuli

• Heart rate

  Heart rate will be recorded during the task.

  Immediately after pain/rejection stimuli

Secondary Outcomes (2)

• Whole-brain maps of intervention effects

  Immediately after pain/rejection stimuli

• Rejection Sensitivity Questionnaire

  Within 2 weeks before first fMRI scan

Study Arms (2)

Naloxone Group

EXPERIMENTAL

Participants will receive 4mg naloxone nasal spray.

Drug: Placebo Cream with Naloxone; Drug: Control Cream with Naloxone

Saline Group

EXPERIMENTAL

Participants will receive saline in the nasal spray.

Drug: Placebo Cream with Saline; Drug: Control Cream with Saline

Interventions

Control Cream with Naloxone DRUG

Participants will be informed that the spray is saline.

Naloxone Group

Placebo Cream with Naloxone DRUG

Participants will be informed that the spray is an effective pain and negative emotion reducing agent.

Naloxone Group

Placebo Cream with Saline DRUG

Participants will be informed that the spray is an effective pain and negative emotion reducing agent.

Saline Group

Control Cream with Saline DRUG

Participants will be informed that the spray is saline.

Saline Group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults aged 18-55 years
• No current psychiatric or major neurological diagnosis
• No reported substance abuse within the last six months
• Are capable of performing experimental tasks (e.g., are able to read, able to cooperate with fMRI examination)
• Are fluent or native speakers of English
• No current or recent history of pathological pain or reported neurological disorders.
• Having abstained from alcohol and substance use for 48 hours
• Passed fMRI safety screener
• Experienced a recent unwanted breakup of a romantic relationship

You may not qualify if:

• Current presence of pain
• Current or past history of primary psychiatric disorder
• Current or past history of psychoactive substance abuse or dependence
• Dementias
• Movement disorders except familial tremor
• CNS infection
• CNS vasculitis, inflammatory disease or autoimmune disease
• CNS demyelinating disease (e.g. multiple sclerosis)
• Space occupying lesions (mass lesions, tumors)
• Congenital CNS abnormality (e.g. cerebral palsy)
• Seizure disorder
• History of closed head trauma with loss of consciousness
• History of cerebrovascular disease (stroke, TIAs)
• Abnormal MRI (except changes accounted for by technical factors or UBOs)
• Neuroendocrine disorder (e.g., Cushings disease)

Sponsors & Collaborators

• Trustees of Dartmouth College: lead

Study Sites (1)

Dartmouth College

Hanover, New Hampshire, 03755, United States

Location

MeSH Terms

Conditions

Pain; Rejection, Psychology

Interventions

Naloxone; Sodium Chloride

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Tor D Wager, PhD

  Dartmouth College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tor D Wager, PhD

CONTACT

603-646-2196; Tor.D.Wager@Dartmouth.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Diana L. Taylor Distinguished Professor

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: December 3, 2020
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: All data will be de-identified prior to sharing. Raw data will be submitted to NDA within one year from the end of data collection or 6 months from the acceptance date of the first primary study manuscript on the full dataset (excluding methods development papers), whichever is later. Analyzed data/maps of statistical results and models accompanying each paper will be submitted to NDA/OpenFMRI when the primary study manuscript is accepted.
• Access Criteria: These data would generally be made available to any qualified investigator for neuroimaging studies only including: i. Research on any brain phenomenon; ii. Neuroimaging research on non-disease traits (intelligence, behavioral traits); iii. Methods development research. The requesting investigator must provide documentation of local IRB approval. These data would not be made available to: i. Any criminal justice organization, because data may not be used for any criminal justice applications; ii. Any commercial entity, because use of the data is limited to not-for-profit organizations and data may not be used for any commercial purposes.

Locations

US (1)