Low dose Naltrexone (LDN) for Chronic Pain

Low dose naltrexone (LDN) has been used to treat a number of chronic pain conditions. Although the research is limited, case reports and smaller trials have shown success for patients with post-COVID pain syndrome, fibromyalgia, chronic back pain, and various other central pain syndromes.

LDN (typically dosed 1.5 mg-4.5 mg/day) is well tolerated and inexpensive, making it a great off-label option for refractory pain. It has a very favorable safety profile, which makes it a great choice for patients unable to tolerate other nerve or sedating pain medications. The most common reported side effects are headaches or vivid dreams.

The idea behind LDN is that it acts like a glial modulator, antagonizing Toll-like receptor 4 (TLR4) on microglia and reducing pro-inflammatory cytokines (IL-6, TNF-α, nitric oxide, interferon-β). It also transiently blocks opioid receptors. What does that mean? These actions target central sensitization, which is the method of pain for a lot of chronic, challenging pain syndromes such as fibromyalgia and post-COVID pain syndrome.

For post-COVID pain, LDN has the most favorable research, although still limited, of any chronic pain condition. However, there are still no large scale randomized controlled trials.

Other conditions that have been studied and shown to have benefit with LDN are centralized/neuropathic conditions such as CRPS, burning mouth syndrome, vulvodynia, trigeminal neuropathic pain, and treatment-resistant back pain. Most of these studies have been case reports, case series, and retrospective cohort studies rather than large, randomized controlled trials.

At Revitalize Medical Center, we utilize low dose naltrexone (LDN) for a variety of conditions. If you would like to seek an evaluation, please give us a call at 847-834-4018.

References:

1. Low-Dose Naltrexone: What is the Evidence? A Narrative Review.

Advances in Therapy. 2026. Gouda AHK, Aitcheson NEC, Steadman KJ.RecentReview

2. Managing Pain in Fibromyalgia: Current and Future Options.

Drugs. 2025. Clarke H, Peer M, Miles S, Fitzcharles MA.Review

3. Efficacy of Low-Dose Naltrexone in Women With Fibromyalgia Syndrome: A 12-Month Randomised, Double-Blind, Placebo-Controlled Single-Centre Clinical Trial (INNOVA Study).

European Journal of Pain. 2026. Rodríguez-Freire C, Navarrete J, Rozadilla-Sacanell A, et al.RecentRCT

4. The Utilization of Low Dose Naltrexone for Chronic Pain.

CNS Drugs. 2023. Poliwoda S, Noss B, Truong GTD, et al.

5. Managing Burning Mouth Syndrome: Current and Future Directions.

Drugs. 2025. Sangalli L, Mirfarsi S, Kramer JM, Eisa E, Miller CS.Review

6. Novel Therapies for Centralized Pain: a Brief Review.