NCT04650841

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

• Status: Not Yet Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Trustees of Dartmouth College · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

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.

Detailed description

Background: Loss of close relationships is one of the most aversive life events. An unwanted romantic breakup leads to a 20% risk of developing depression within a month, a dramatic increase in depression risk. The investigators recently identified brain pathways mediating placebo effects on physical heat pain and the social pain associated with an unwanted breakup, including common involvement of dlPFC-PAG pathways and vmPFC. Other recent studies have identified rejection-related opioidergic activity in these circuits that may reflect endogenous regulatory mechanisms. This experiment probes the involvement of the opioid system in placebo effects on social pain, using the opioid antagonist naloxone. Design: Extending the investigator's previous design, participants who recently experienced an unwanted breakup will submit pictures of their ex-partners, places associated with strong memories of the partner, and written descriptions of memories that evoke rejection and social pain. Participants will 1) experience rejection-related stimuli and 2) receive painful heat and pressure stimuli in separate runs during fMRI scanning. FMRI scans after Control and Placebo treatment-nasal spray with suggestions of efficacy for emotion and pain-will be performed in a 2-session within-person counterbalanced design. Participants will be randomized into two groups that receive either (1) 4mg naloxone nasal spray or (2) saline in the nasal spray in both sessions, implementing a 2 x 2 (Placebo/Control x Saline/Naloxone) design.

Conditions

• Pain
• Rejection
• Placebo Effect

Interventions

Type	Name	Description
DRUG	Placebo Cream with Naloxone	Participants will be informed that the spray is an effective pain and negative emotion reducing agent.
DRUG	Control Cream with Naloxone	Participants will be informed that the spray is saline.
DRUG	Placebo Cream with Saline	Participants will be informed that the spray is an effective pain and negative emotion reducing agent.
DRUG	Control Cream with Saline	Participants will be informed that the spray is saline.

Timeline

• Start date: 2026-09-01
• Primary completion: 2027-03-01
• Completion: 2027-03-01
• First posted: 2020-12-03
• Last updated: 2025-12-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study