A targeted pharmacotherapy approach to aid opioid tapering

SHORT DESCRIPTION
A pharmacotherapy to improve opioid tapering success by countering opioid-induced adaptations in cortical receptor activity.

• Apkar Apkarian*
  • Principal Investigator
• Marwan Baliki

NU Tech ID: NU 2025-023

IP STATUS

US Patent Pending

DEVELOPMENT STAGE

TRL-1 - Basic Principles Observed: Implicated receptors identified in human studies and validated in mouse model

BACKGROUND
Chronic pain affects over 20% of the world’s population and is a leading cause of disability. Current pain management strategies often rely on opioids, which can lead to misuse, opioid use disorder, and significant societal burden. Beyond these known issues, neurobiological and psychological consequences of long-term opioid use remain a risk as these effects are largely unexplored. A major challenge lies in safely and effectively tapering patients off opioids, with existing tapering protocols failing in over 50% of patients due to the complex interplay of pain and opioid-induced neuroadaptations. There is a critical unmet need for targeted pharmacotherapies that can alleviate negative side effects and improve overall success rates of opioid tapering.

ABSTRACT
Through investigations into neural circuit adaptations caused by long-term opioid use, Northwestern researchers have identified a clinically actionable molecular target and candidate drug for aiding opioid tapering. Researchers analyzed cortical receptor-related activity in chronic back pain patients on long-term opioid therapy and found that these patients exhibited hyperactivity in opioidergic circuits and hypoactivity in serotonergic circuits, changes that were associated with increased functional disability and negative affect. These neurobiological adaptations were further validated in a mouse model of long-term opioid exposure. In a proof-of-concept study in healthy volunteers, the researchers demonstrated that the serotonergic agonist vortioxetine modulated neural circuit activity in a manner opposite to the alterations observed in long-term opioid users, supporting its potential as a therapeutic strategy to improve opioid tapering outcomes.

APPLICATIONS

• Opioid tapering treatment: May improve success rates in reducing long-term opioid dependence in chronic pain patients.
• Chronic pain management: Can serve as an adjunct therapy to optimize overall pain management strategies.

ADVANTAGES

• Improves tapering success: Targets specific molecular receptors for a biologically informed tapering treatment plan.
• Leverages existing medicine: Repurposes FDA-approved drug to accelerate commercial development timeline.
• Supports translational validation: Integrates human data and animal model proof-of-concept for robust evidence.

PUBLICATIONS

• Marwan Baliki, Apkar Apkarian, Andrew Vigotsky et al. "Multi-receptor whole-cortex adaptations with long-term opioid use in chronic pain." Research Square, 2024.

KEYWORDS
Pain management, opioid tapering, molecular targets, vortioxetine, chronic pain, translational research