Low-dose naltrexone

Mechanism of action

Naltrexone and its active metabolite 6-β-naltrexol are competitive antagonists at μ-opioid and κ-opioid receptors, and to a lesser extent at δ-opioid receptors. Standard therapeutic doses of naltrexone block these receptors, which does two things; it prevents inhibition of GABA receptors (normally, signaling through the GABA receptors inhibits the activity of neurons; many recreational drugs inhibit GABA and thus "free up" neuronal activation; preventing inhibition of GABA allows GABA's normal inhibition activity to take place) and it blocks dopamine release (many recreational drugs stimulate dopamine release, which is part of the brain's reward system that creates pleasure).

Research

Multiple studies have shown that low-dose naltrexone has promise as a treatment for chronic pain, some autoimmune disorders and cancers. Studies on the efficacy of low-dose naltrexone for multiple sclerosis (MS) have been inconclusive. Clinical trials for treatment of fibromyalgia were initiated in 2021.

Low-dose naltrexone is also being studied in long COVID.

A 2018 therapeutic utilization review concluded that low-dose naltrexone may be an appropriate option for treatment of fibromyalgia and irritable bowel disease, but that "Proper clinical trials are needed in order to establish evidence that could lead to correct indications, mode of administration, and other aspects necessary for effective clinical pharmacology of [low-dose naltrexone]." The UK's National Health Service echoed this sentiment in 2020.

Younger et al. (2014) found reduced pro‑inflammatory cytokines and self‑reported pain in fibromyalgia patients using LDN. A 2018 review summarized mixed trial outcomes and emphasized methodological limitations.

A 2023 systematic review published in the Australian Journal of General Practice found that preliminary research into the use of low-dose naltrexone as a treatment for fibromyalgia is promising. All clinical studies examined showed statistically significant improvements in pain and pain tolerance with mild side effects, however, sample sizes were small and the evidence is inconclusive.

A 2025 scoping review article recommended larger, placebo‑controlled Randomized controlled trials with standardized dosing and long‑term follow‑up to establish efficacy and appropriate clinical indications.

References

sv:Låg dos Naltrexon

References

1. (2014-02-15). "The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain". Springer Science and Business Media LLC.
2. (2020). "Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review". Current Pain and Headache Reports.
3. Sudakin, Daniel. (2015-11-06). "Naltrexone: Not Just for Opioids Anymore". Springer Science and Business Media LLC.
4. Bihari, Bernard. (2013). "Bernard Bihari, MD: low-dose naltrexone for normalizing immune system function". Alternative Therapies in Health and Medicine.
5. (2018-09-21). "Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization". MDPI AG.
6. (24 July 2013). "Targeted Opioid Receptor Antagonists in the Treatment of Alcohol Use Disorders". CNS Drugs.
7. Papantoniou, E. (2024-04-17). "What to Avoid When Taking Low Dose Naltrexone - Trinova Health".
8. (26 August 2020). "Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review". [[Current Pain and Headache Reports]].
9. (April 2014). "The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain". [[Clinical Rheumatology]].
10. (August 2018). "Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy". International Immunopharmacology.
11. (2017). "Low dose naltrexone in multiple sclerosis: Effects on medication use. A quasi-experimental study". PLOS ONE.
12. (2016). "Long-term treatment with low dose naltrexone maintains stable health in patients with multiple sclerosis". Multiple Sclerosis Journal - Experimental, Translational and Clinical.
13. (December 2021). "Low-dose naltrexone for the treatment of fibromyalgia: protocol for a double-blind, randomized, placebo-controlled trial". Trials.
14. (18 October 2022). "Addiction drug shows promise lifting long COVID brain fog, fatigue". Reuters.
15. (October 2022). "Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study". Brain, Behavior, & Immunity — Health.
16. (2018). "Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization". Medical Sciences.
17. Eve, Marianne. (5 February 2020). "What is the evidence for low dose naltrexone for treatment of multiple sclerosis?". [[National Health Service]].
18. (2013). "Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study". Arthritis & Rheumatology.
19. (2018). "Low-dose naltrexone (LDN)—review of therapeutic utilization". Medical Sciences.
20. (2023). "Low-dose naltrexone in the treatment of fibromyalgia: A systematic review and narrative synthesis". Royal Australian College of General Practitioners.
21. Leiber, Kayla K.. (2025). "Therapeutic Uses and Efficacy of Low-Dose Naltrexone: A Scoping Review of Human Clinical Trials". Cureus.