Prospective of low dose naltrexone use in treatment of autoimmune pathology and endometriosis

In: REPRODUCTIVE ENDOCRINOLOGY · 2020 · pp. 53–57 · doi:10.18370/2309-4117.2020.55.53-57 · W3111751216
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Low dose naltrexone increases endogenous endorphins and enkephalins, potentially benefiting the immune system and cell growth, with evidence suggesting efficacy in autoimmune conditions and tumors.

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The paper discusses low-dose naltrexone (LDN) at 1.7–5 mg as a prospective therapy for autoimmune pathology in gynecology and reproductology, with endometriosis highlighted, proposing that receptor blockade produces a rebound increase in endogenous endorphins and enkephalins that modulates immune processes and inflammatory cytokine production. It summarizes evidence from clinical trials primarily in Crohn’s disease and multiple sclerosis, and it also describes mechanistic hypotheses involving reduced nitric oxide synthase activity and effects on T- and B-lymphocytes and toll-like receptor signaling, while noting that LDN remains off-label in autoimmune conditions. A caveat emphasized is that the evidence base includes limited trial types and that safety data across doses, including mid-therapeutic use during pregnancy, are reported but the broader clinical context is still evolving. Relevance to endometriosis: the paper is about endometriosis and includes prior findings such as an association between endometriosis and altered mu-opioid receptor expression, using these links to support its argument that LDN may be effective for endometriosis, though it reviews other autoimmune diseases for clinical trial data.

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Abstract

There are still many complex issues in the management of autoimmune pathologies in gynecology and reproductology, endometriosis in particular. Naltrexone, a competitive antagonist of opiate receptors in the central and peripheral nervous systems, reveals new qualities such as effects on autoimmune processes. Naltrexone in low doses of 1.7–5 mg (Low Dose Naltrexone, LDN) revealed the opposite effect on opiate receptors in the form of a rebound effect and, as a consequence, a strong increase in endogenous endorphins and enkephalins. Studies of elevated levels of these neurotransmitters have provided evidence of a multidisciplinary beneficial effect on the immune system of people with endorphin and enkephalin deficiency, an association between the endogenous opiate system and cells and tissue growth in general and healthy immune function was confirmed. The most explored effects of them are such as blocking the synthesis ofpro inflammatory cytokines IL-6, IL-12, tumor necrosis factor, the effect on neuroglia through toll-like receptors, the effect on the cycle cells growth, especially malignant tumor cells, through interaction with opiate growth factor, modulation synthesis of T- and B-lymphocytes. Growing evidence of LDN efficacy is becoming a potentially effective clinical practice in autoimmune pathologies, but still off-label used.Some data of clinical trials is presented. Four studies with Crohn's disease with results of relief of symptoms and remission, including experience in pediatrics. Three clinical trials with LDN results in multiple sclerosis with improved quality of life and improved symptoms. The scientific hypothesis suggests the success of LDN due to the reduction of induced nitric oxide synthase activity. The success of management of patients with malignant tumors is also presented. The article contains the latest data from clinical trials on reported serious and non-serious side effects of naltrexone at various doses, including data confirming the safety of taking mid-therapeutic naltrexone doses throughout pregnancy. These effects of LDN may prove to be effective in management patients with endometriosis.
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Prospective of low dose naltrexone use in treatment of autoimmune pathology and endometriosis DOI: https://doi.org/10.18370/2309-4117.2020.55.53-57Keywords: naltrexone, autoimmune pathology, pregnancy, endometriosisAbstract There are still many complex issues in the management of autoimmune pathologies in gynecology and reproductology, endometriosis in particular. Naltrexone, a competitive antagonist of opiate receptors in the central and peripheral nervous systems, reveals new qualities such as effects on autoimmune processes. Naltrexone in low doses of 1.7–5 mg (Low Dose Naltrexone, LDN) revealed the opposite effect on opiate receptors in the form of a rebound effect and, as a consequence, a strong increase in endogenous endorphins and enkephalins. Studies of elevated levels of these neurotransmitters have provided evidence of a multidisciplinary beneficial effect on the immune system of people with endorphin and enkephalin deficiency, an association between the endogenous opiate system and cells and tissue growth in general and healthy immune function was confirmed. The most explored effects of them are such as blocking the synthesis of pro inflammatory cytokines IL-6, IL-12, tumor necrosis factor, the effect on neuroglia through toll-like receptors, the effect on the cycle cells growth, especially malignant tumor cells, through interaction with opiate growth factor, modulation synthesis of T- and B-lymphocytes. Growing evidence of LDN efficacy is becoming a potentially effective clinical practice in autoimmune pathologies, but still off-label used. Some data of clinical trials is presented. Four studies with Crohn's disease with results of relief of symptoms and remission, including experience in pediatrics. Three clinical trials with LDN results in multiple sclerosis with improved quality of life and improved symptoms. The scientific hypothesis suggests the success of LDN due to the reduction of induced nitric oxide synthase activity. The success of management of patients with malignant tumors is also presented. The article contains the latest data from clinical trials on reported serious and non-serious side effects of naltrexone at various doses, including data confirming the safety of taking mid-therapeutic naltrexone doses throughout pregnancy. These effects of LDN may prove to be effective in management patients with endometriosis. References - Sudakin, D. “Naltrexone: Not Just for Opioids Anymore.” J Med Toxicol 12.1 (2016): 71–5. 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DOI: 10.1186/s12916-018-1242-0 - Towers, C.V., et al. “Use of Naltrexone in treating pregnant women with opioid use disorder (OUD).” American Journal of Obstetrics and Gynecology 220.1 (2019): S109. DOI: 10.1016/j.ajog.2018.11.162 - Wachman, E.M., et al. “Naltrexone Treatment for Pregnant Women With Opioid Use Disorder Compared With Matched Buprenorphine Control Subjects.” Clinical Therapeutics 41.9 (2019). DOI: 10.1016/j.clinthera.2019.07.003 Downloads Published How to Cite Issue Section License Copyright (c) 2020 O. V. Golianovskyi, O. O. Andrienko, O. V. Furman, Phil Boyle This work is licensed under a Creative Commons Attribution 4.0 International License. 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