Real-World Effectiveness and Tolerability of Low Dose Naltrexone to Treat Chronic Pain: A Retrospective Cohort Study of One Pain Physician’s Practice

Journal of Pain Research, Volume 18

Authors: Hannah Aalto, Sara Paul & Virginia McEwen

Published 10 December 2025 Volume 2025:18 Pages 6637—6649

https://www.dovepress.com/real-world-effectiveness-and-tolerability-of-low-dose-naltrexone-to-tr-peer-reviewed-fulltext-article-JPR

Purpose: Low-dose naltrexone (LDN) is an off-label treatment for chronic pain, with evidence supporting its use mainly consisting of small-scale studies. This retrospective cohort review aimed to contribute to this growing body of literature and evaluate the real-world effectiveness of LDN across a range of chronic pain conditions in a single physician’s practice.

Patients and Methods: A total of 128 patients prescribed LDN between September 2021 and June 2024 were reviewed independently by two investigators, with 93 meeting inclusion criteria. Patients were categorized into 12 groups based on diagnosis, with fibromyalgia representing the largest subgroup (27 patients). Retrospective cohort data was collected and included patient demographics, adverse effects, dosage, duration of therapy, and reported symptom relief. Descriptive statistics were used to analyze findings.

Results: Subjective symptom relief was reported by 53.8% of patients, most commonly improvements in pain (49 patients) and fatigue (25 patients), when taking LDN. The highest response rates were seen in patients with mast cell activation syndromes and arthritis-related conditions (71.4%). Adverse effects occurred in 49.5% of patients, most frequently nausea and fatigue. No serious adverse effects were reported.

Conclusion: These findings suggest that LDN may be an effective and well-tolerated treatment option for a range of chronic pain conditions. Further studies, such as randomized controlled trials, are warranted to confirm these results and optimize dosing strategies.