Ewelina Mundzik-Janczarska, Andrzej Stańczak

Low Dose Naltrexone – Efficacy and safety of off-label use therapy
2020-01-10

Naltrexone is well-known opioid antagonist used in chronic or acute states of abuse, respectively. Nowadays the low doses of this drug are gaining popularity among researchers, doctors and patients seeking alternatives to well-known and widely used therapies in various indications. The low-dose naltrexone (LDN) is the therapy which involving the use of naltrexone at daily doses 10 times lower or even lower (usually 1 mg - 5 mg) than in the approved by Food and Drug Administration and European Medicines Agency. The therapy is usually prepared by using pure substance (obtained from manufacturer) or by preparing appropriate dosage from drug available on the market. In accordance with available reports low dosage of naltrexone may acts through short-term and intermittent binding to opioid receptors causes a compensatory increase in endogenous opioids including β-endorphins and increase in expression of μ and δ receptors. The LDN also binds briefly the opioid growth factor receptor (OGFr), causing blockage of binding to opioid growth factor (OGF, met-enkephalin). The researchers also believe that low-dose naltrexone is antagonist of TLR4 receptor and acts as glial cells modulator. Based on the mechanism of action of low-doses of naltrexone, which is not fully known, researchers are trying to confirm reports concerning the efficacy and safety of the therapy in many diseases, including autoimmune disorders (including Crohn’s disease, multiple sclerosis), fibromyalgia and chronic pain, cancer or dermatological diseases. The safety profile of naltrexone at standard doses (50–100 mg) is well known when the drug is used in accordance with registered indications. The information on the safety of LDN treatment protocol is still limited and the data collected is insufficient. Preliminary reports may suggest that treatment is relatively safe however, to confirm safety profile and effects of chronic use it is necessary to conduct extensive, long-term studies in large, varied populations. Despite the lack of registration in any indication and necessity of conducting extensive research on the safety and effectiveness of its use, this therapy has gained a wide range of supporters among both doctors and patients and has been adopted as an alternative off-label treatment. If the effectiveness and safety of LDN are confirmed, it will be undoubtedly a breakthrough therapy, willingly used by patients around the world due to its low cost, availability, safety profile and easy to use.

Keywords: LDN, low-dose naltrexone, fibromyalgia, Crohn’s disease, multiple sclerosis, off-label.

© Farm Pol, 2019, 75(12): 676–686