Introduction to Low Dose Naltrexone

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Low-dose naltrexone (LDN) is a medication that has been gaining attention in recent years for its potential therapeutic benefits in various medical conditions. In this comprehensive guide, we will explore what LDN is, its pharmacological mechanism of action, its uses, benefits, risks, and potential side effects.

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What is Low-Dose Naltrexone?

Naltrexone is a competitive opioid receptor antagonist that is typically used to treat opioid and alcohol dependence Rodriguez et al., 2023. However, when used in low doses, typically ranging from 0.1 to 4.5 mg per day, it has been found to have therapeutic effects in various conditions, including chronic pain, fibromyalgia, and multiple sclerosis J Marcus et al., 2024.

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Pharmacological Mechanism of Action

Naltrexone works by blocking the opioid receptors in the brain, which can help to reduce the perception of pain and inflammation B Margolis et al., 2022. It also has anti-inflammatory properties, which can help to reduce the production of pro-inflammatory cytokines C. Toledano, 2021.

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Uses of Low-Dose Naltrexone

LDN has been used to treat a variety of conditions, including:
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• Chronic pain: LDN has been found to be effective in reducing chronic pain in patients with fibromyalgia and other chronic pain conditions Bruun-Plesner et al., 2020.
• Fibromyalgia: LDN has been found to be effective in reducing symptoms of fibromyalgia, including pain, fatigue, and sleep disturbances B Weinstock et al., 2020.
• Multiple sclerosis: LDN has been found to be effective in reducing symptoms of multiple sclerosis, including fatigue, pain, and cognitive impairment Mohammed Dheyaa Marsool Marsool et al., 2024.
• Autoimmune disorders: LDN has been found to be effective in reducing symptoms of autoimmune disorders, including rheumatoid arthritis and lupus Carmona-Rivera & J Kaplan, 2022.

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Benefits of Low-Dose Naltrexone

The benefits of LDN include:
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• Reduced pain and inflammation: LDN has been found to be effective in reducing chronic pain and inflammation in various conditions B Margolis et al., 2022.
• Improved mood: LDN has been found to have antidepressant effects and can help to improve mood in patients with depression C. Toledano, 2021.
• Improved sleep: LDN has been found to improve sleep quality in patients with insomnia and other sleep disorders Bruun-Plesner et al., 2020.
• Reduced fatigue: LDN has been found to reduce fatigue in patients with chronic fatigue syndrome and other conditions J Marcus et al., 2024.

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Risks and Side Effects of Low-Dose Naltrexone

The risks and side effects of LDN include:
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• Nausea and vomiting: LDN can cause nausea and vomiting, especially when first starting the medication S Smith et al., 2022.
• Headache: LDN can cause headaches, especially when first starting the medication S Smith et al., 2022.
• Fatigue: LDN can cause fatigue, especially when first starting the medication J Marcus et al., 2024.
• Insomnia: LDN can cause insomnia, especially when first starting the medication Bruun-Plesner et al., 2020.
• Allergic reactions: LDN can cause allergic reactions, including hives, itching, and difficulty breathing S Smith et al., 2022.

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Conclusion

Low-dose naltrexone is a medication that has been found to have therapeutic benefits in various medical conditions, including chronic pain, fibromyalgia, and multiple sclerosis. While it has several benefits, it also has potential risks and side effects, including nausea, headache, fatigue, insomnia, and allergic reactions. Further research is needed to fully understand the effects of LDN and to determine its potential uses in various medical conditions.

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References

Cited References:

Rodriguez, F., Carvalho, M., & Banov, F. (2023). Case study: personalized oral low-dose naltrexone titration for pain management.. International Journal Of Pharmaceutical Compounding. https://pubmed.ncbi.nlm.nih.gov/38100664
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J Marcus, N., Robbins, L., Araki, A., J Gracely, E., & C Theoharides, T. (2024). Effective doses of low-dose naltrexone for chronic pain - an observational study.. Journal Of Pain Research. https://doi.org/10.2147/JPR.S451183
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B Margolis, E., G Moulton, M., S Lambeth, P., & J O'Meara, M. (2022). The life and times of endogenous opioid peptides: updated understanding of synthesis, spatiotemporal dynamics, and the clinical impact in alcohol use disorder. Neuropharmacology. https://doi.org/10.1016/j.neuropharm.2022.109376
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C. Toledano, A. (2021). The acute treatment of migraine with low-dose naltrexone and acetaminophen combinations and each component: findings of a small, randomized, double-blind, and placebo-controlled clinical trial. MedRxiv. https://doi.org/10.1101/2021.03.22.21254145
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Bruun-Plesner, K., Rune Blichfeldt-Eckhardt, M., Bjarke Vaegter, H., T Lauridsen, J., Amris, K., & Toft, P. (2020). Low-dose naltrexone for the treatment of fibromyalgia: investigation of dose-response relationships.. Pain Medicine (Malden, Mass.). https://doi.org/10.1093/pm/pnaa001
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B Weinstock, L., Cottel, J., Aldridge, L., & Egeberg, A. (2020). Low-dose naltrexone therapy for psoriasis.. International Journal Of Pharmaceutical Compounding. https://pubmed.ncbi.nlm.nih.gov/32196470
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Mohammed Dheyaa Marsool Marsool, M., Prajjwal, P., John, J., S Keluskar, H., V Sivarajan, V., A Kundiri, K., R Lam, J., Chavda, S., G Atew, H., Ali Dheyaa Marsool Marsool, A., Al-Tuaama A Z Hameed, A., & A Hussin, O. (2024). Association of multiple sclerosis with stroke: a comprehensive review.. Health Science Reports. https://doi.org/10.1002/hsr2.1837
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Carmona-Rivera, C. & J Kaplan, M. (2022). Low-density granulocytes in systemic autoimmunity and autoinflammation.. Immunological Reviews. https://doi.org/10.1111/imr.13161
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S Smith, S., Cernaro, N., & Tonti, E. (2022). Eosinophilic pustular folliculitis due to naltrexone: a case report.. Journal Of The American Pharmacists Association : JAPhA. https://doi.org/10.1016/j.japh.2022.07.007
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Relevant but not cited:
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Shahbazi Nia, S., T Ortiz, Y., D Zuarth Gonzalez, J., Shamir, L., Frimpong-Manson, K., Anwar Hossain, M., Shahi, S., Bandy, R., Bhat, A., Patel, D., Diab, H., Thompson, J., R McMahon, L., L Wilkerson, J., & A German, N. (2024). Characterization of a nonselective opioid receptor functional antagonist: implications for development as a novel opioid dependence medication.. ACS Pharmacology & Translational Science. https://doi.org/10.1021/acsptsci.3c00262
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L Withey, S., Bergman, J., & A Paronis, C. (2023). The effects of chronic naltrexone on reinstatement of opioid-induced drug-seeking behavior and antinociception.. The Journal Of Pharmacology And Experimental Therapeutics. https://doi.org/10.1124/jpet.122.001570
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A Higginbotham, J., Markovic, T., Massaly, N., & A Morón, J. (2022). Endogenous opioid systems alterations in pain and opioid use disorder.. Frontiers In Systems Neuroscience. https://doi.org/10.3389/fnsys.2022.1014768
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Liu, K., Gao, Y., Wu, X., Hu, X., Shi, C., He, Q., Wu, H., Yao, H., Ma, D., Yang, J., & Ji, M. (2024). Microglia phagocytosis of pnns mediates pv-positive interneuron dysfunction and associated gamma oscillations in neuroinflammation-induced cognitive impairment in mice.. Neuropharmacology. https://doi.org/10.1016/j.neuropharm.2024.110205
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J Risen, S., W Boland, S., Sharma, S., M Weisman, G., M Shirley, P., S Latham, A., Arielle J D Hay, A., S Gilberto, V., D Hines, A., Brindley, S., M Brown, J., McGrath, S., Chatterjee, A., Nagpal, P., & A Moreno, J. (2024). Targeting neuroinflammation by pharmacologic downregulation of inflammatory pathways is neuroprotective in protein misfolding disorders.. ACS Chemical Neuroscience. https://doi.org/10.1021/acschemneuro.3c00846
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Aitcheson, N., Lin, Z., & Tynan, K. (2023). Low-dose naltrexone in the treatment of fibromyalgia: a systematic review and narrative synthesis.. Australian Journal Of General Practice. https://doi.org/10.31128/AJGP-09-22-6564
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Gao, Y., Wang, Y., Li, R., & Zhou, X. (2021). Comprehensive analysis of clinical trials registration for lupus nephritis therapy on clinicaltrials.gov.. Frontiers In Medicine. https://doi.org/10.3389/fmed.2021.680302
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R Ehrenstein, M. & Shipa, M. (2023). Sle is not a one-size-fits-all disease.. The Journal Of Experimental Medicine. https://doi.org/10.1084/jem.20230559
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Goel, A., Kapoor, B., Wu, M., Iyayi, M., Englesakis, M., Kohan, L., S Ladha, K., & A Clarke, H. (2024). Perioperative naltrexone management: a scoping review by the perioperative pain and addiction interdisciplinary network.. Anesthesiology. https://doi.org/10.1097/ALN.0000000000005040
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Bielekova, B., Wu, T., Kosa, P., & Calcagni, M. (2024). Data-driven risk/benefit estimator for multiple sclerosis therapies. MedRxiv. https://doi.org/10.1101/2024.08.16.24312134
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Hee Tay, S., Celhar, T., & Fairhurst, A. (2020). Low-density neutrophils in systemic lupus erythematosus.. Arthritis & Rheumatology (Hoboken, N.J.). https://doi.org/10.1002/art.41395
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T Carreno-Davidson, J., M Castellani, C., J Carreno, J., P DeLuca, J., J Selig, D., V Vuong, C., M Pasiakos, S., & M Ritland, B. (2023). Daily naltrexone use does not adversely affect physical, cognitive or marksmanship performance in u.s. army soldiers.. Military Medicine. https://doi.org/10.1093/milmed/usad325
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J Onakpoya, I., J Lee, J., R Mahtani, K., K Aronson, J., & J Heneghan, C. (2020). Naltrexone-bupropion (mysimba) in management of obesity: a systematic review and meta-analysis of unpublished clinical study reports.. British Journal Of Clinical Pharmacology. https://doi.org/10.1111/bcp.14210
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P Drozda Jr, J., Ssemaganda, H., A Frankenberger, E., Brandt, E., Robbins, S., Khairnar, N., Cha, A., & S Resnic, F. (2024). Testing a cloud-based model for active surveillance of medical devices with analyses of coronary stent safety using the data extraction and longitudinal trend analysis (delta) system.. Medical Devices (Auckland, N.Z.). https://doi.org/10.2147/MDER.S445160
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Gujral, H., Sharma, A., Jain, P., Juneja, S., & Mittal, S. (2022). Design and implementation of a quantitative network health monitoring and recovery system.. Wireless Personal Communications. https://doi.org/10.1007/s11277-022-09554-9