Efficacy of Ketamine Infusion for Treatment of Opioid Use Disorder in Patients with Chronic Pain: a Narrative Review.

Summary

Ketamine, an NMDA receptor antagonist, shows promise as an adjunctive treatment for patients with both chronic pain and opioid use disorder. It blocks NMDA receptors, reducing neural excitability and promoting neuroplastic changes that may help manage pain and reduce opioid dependence. Clinical studies suggest ketamine can reduce pain severity, decrease opioid consumption, and alleviate withdrawal symptoms in select populations. However, evidence is limited by small sample sizes, non-standardized protocols, and short follow-up periods. Side effects include dissociative symptoms, sympathomimetic activity, and potential for misuse, requiring careful patient selection and monitoring. Ketamine is a promising option in multimodal care when conventional therapies fail, but further research is needed.

Study at a glance

Abstract

Chronic pain and opioid use disorder (OUD) are highly prevalent and frequently co-occurring conditions that pose complex treatment challenges. While opioids are effective for pain management, prolonged use significantly enhances risk of developing substance dependence. Conversely, addiction-focused therapies often fail to relieve persistent somatic pain. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a novel adjunctive treatment with potential to address chronic pain and substance use disorders concurrently. The present investigation examines the role of intravenous ketamine infusions in cases with coexisting chronic pain and OUD. It explores pharmacological mechanisms, therapeutic applications, clinical efficacy, and safety considerations of ketamine. Ketamine primarily acts by blocking NMDA receptors, which are central to glutamatergic signaling. This inhibition reduces neural excitability and promotes neuroplastic changes, including upregulation of brain-derived neurotrophic factor (BDNF), a protein associated with synaptic remodeling and recovery within pain and addiction pathways. These mechanisms are likely to contribute to ketamine mediated dual efficacy in managing nociceptive symptoms and reducing opioid dependence. Clinical studies suggest that ketamine may reduce pain severity, decrease opioid consumption, and alleviate withdrawal symptoms in select populations. While early evidence supports ketamine's use, its side effect profile, including dissociative symptoms, sympathomimetic activity, and potential for misuse, necessitates careful patient selection, monitoring, and oversight. Evidence remains limited by inadequate sample sizes, non-standardized protocols, and short follow-up periods. Despite these limitations, ketamine remains a promising adjunct in multimodal care, especially when conventional therapies are ineffective. Ongoing research is essential to refine protocols and to explore integration with behavioral and pharmacologic addiction interventions.