Low-dose naltrexone

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==