NCT06786637

Investigating the Protective Impact of LY-2940094 on Stress-induced Depression- and Anxiety-related Phenotypes in Humans

A Combined Investigation of the Protective Impact of the NOF/Q Antagonist LY-2940094 on Stress-induced Depression- and Anxiety-related Phenotypes in Humans

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Mclean Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

This project will integrate pharmacological and psychophysiological methodology to mechanistically investigate, in humans, the role of N/OFQ in laboratory phenotypes of both disorders. Specifically, a N/OFQ receptor (NOPR) antagonist will be used to test the hypothesis that NOPR blockage will have antidepressant-like effects (potentiate reward processing); in addition, this study will also evaluate a key anxiety phenotype (fear learning). Finally, the impact of recent life stress on these processes will be assessed. Results will demonstrate the specificity of NOPR blockage on depressive phenotypes or suggest a common pathway for emotional disorders and will confirm a modulatory role of life stress.

Conditions

• Depression - Major Depressive Disorder
• Anxiety
• Stress

Interventions

Type	Name	Description
DRUG	Nociceptin Receptor Antagonist (LY-2940094)	Participants in the experimental arms will receive 40 mg of the nociceptin receptor antagonist LY-2940094. Peak concentrations are achieved 2-4 hours post-administration.
DEVICE	DS8R Biphasic Constant Current Stimulator	As part of the fear conditioning task, electrotactile stimulation will be used. The aversive stimulus is delivered in the form of a mild half-second stimulation to the ankle, calibrated to a subjective threshold that is uncomfortable but not painful. This stimulation is delivered by Digitimer DS8R Constant Current Stimulator (Digitimer North America, LLC. Ft. Lauderdale, FL). This model has been safely implemented in studies within McLean Hospital and Massachusetts General Hospital.

Timeline

• Start date: 2025-06-01
• Primary completion: 2026-01-01
• Completion: 2026-08-01
• First posted: 2025-01-22
• Last updated: 2025-09-25

Regulatory

• FDA-regulated drug study