# Low-dose naltrexone

Low-dose naltrexone (LDN) refers to daily naltrexone dosages that are roughly one-tenth of the standard opioid addiction treatment dosage. Most published research suggests a daily dosage of 4.5 mg, but this can vary by a few milligrams. Low-dose naltrexone has been studied for the treatment of multiple chronic pain disorders including fibromyalgia, multiple sclerosis, Crohn’s disease, and complex regional pain syndrome.
Naltrexone is approved by the Food and Drug Administration (FDA) for medication-assisted treatment of alcoholism and opioid use disorders. Bernard Bihari's initial off-label usage of naltrexone in doses ranging from 1.5 mg to 3 mg as an adjuvant therapy for acquired immune deficiency syndrome (AIDS) in the 1980s led to the introduction of LDN into clinical practice. Due to a lack of large-scale clinical trials and standardized research aimed at determining appropriate indications for LDN, it has remained an off-label option.

## 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). As Naltrexone is a competitive antagonist at the identical sites of action of many opioid agonists, such as morphine, care must be taken to ensure that Low-dose naltrexone is not taken near the same time as these medications, as they will not be as efficacious in relieving pain.

## Research

Multiple studies have shown that low-dose naltrexone has promise as a treatment for chronic pain, some autoimmune disorders and cancers. As of 2014, no peer-reviewed studies supporting low-dose naltrexone for multiple sclerosis (MS) have been published. Clinical trials for treatment of fibromyalgia were initiated in 2021.
Low-dose naltrexone is also being studied in long COVID. However, efficacy has not been shown.
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.
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 further research is needed.