Low Dose Naltrexone for Refractory Cancer Pain: Case Series of Initial Safety and Effectiveness

J Pain Symptom Manage. 2025 Dec;70(6):e492-e497. doi: 10.1016/j.jpainsymman.2025.08.015. Epub 2025 Aug 21.

Abstract

Context: Low dose naltrexone (LDN) has been utilized off-label for chronic non-cancer pain; its benefits in treating cancer-related pain remain unclear.

Objectives: We describe the safety and effectiveness of LDN therapy from initiation to the first two follow-up visits in treating refractory cancer-pain.

Methods: Medical charts of cancer patients seen in the Pain Management Center who were prescribed LDN between 2022 and 2023 were reviewed. They were classified as "responders" if they attributed improvement in their primary pain complaints to LDN therapy.

Results: Among the 20 cancer patients who were prescribed LDN, the most common cancer diagnosis was breast cancer (45%). There were 10 patients with cancer burden-related pain and 10 patients with therapy-related pain. Positive response rates of 80% (16/20), and 76.9% (10/13) were recorded at the first and second follow-up visits, respectively which occurred at a mean (SD) of 65.9 (53.3), and 104.8 (60.4) days following LDN initiation, respectively. The most common maximum titration dose of naltrexone was 3.0 mg daily (n = 9) (range 1.5-4.5 mg daily). Therapy-related neuropathy accounted for seven cases with a 71% positive response rate in this subset at the first follow-up. Minor adverse events were noted in two patients (insomnia, GI upset) at the first follow-up; these did not require discontinuation of LDN. The discontinuation rate by the second follow-up was 15% (3/20) (two with inadequate pain relief, one with diarrhea).

Conclusion: Early follow-up indicates potential benefits for patients with refractory cancer pain with LDN being well-tolerated, with a low incidence of adverse events.

Keywords: Low dose naltrexone; cancer pain; chronic pain; non-opioid analgesia.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / physiopathology
  • Cancer Pain* / drug therapy
  • Female
  • Gastrointestinal Tract / drug effects
  • Humans
  • Intractable Pain* / drug therapy
  • Male
  • Middle Aged
  • Naltrexone* / administration & dosage
  • Naltrexone* / adverse effects
  • Narcotic Antagonists* / administration & dosage
  • Narcotic Antagonists* / adverse effects
  • Neoplasm Metastasis / physiopathology
  • Neoplasms* / physiopathology
  • Retrospective Studies
  • Sleep Initiation and Maintenance Disorders / chemically induced
  • Treatment Outcome

Substances

  • Naltrexone
  • Narcotic Antagonists