Biology:Low-dose naltrexone
Low-dose naltrexone (LDN) describes the off-label, experimental use of the medication naltrexone at low doses for diseases such as Crohn's disease, Hashimoto's and multiple sclerosis, but evidence for recommending such use is lacking.[1][2]
Naltrexone is typically prescribed for opioid dependence or alcohol dependence, as it is a strong opioid antagonist. It has been hypothesized that low-dose naltrexone might operate as an anti-inflammatory agent and therefore could be used to treat some chronic conditions involving immune system dysregulation.
Mechanism of action
Action of naltrexone at normal dose
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.[3] 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).[3]
Hypothesized action at low doses
Low-dose naltrexone refers to doses about 1/10th the size of the dose used normally, typically 4.5 mg or within a couple of milligrams of that value.[4] It is hypothesized that if there are any effects, low-dose naltrexone may inhibit opioid receptors and therefore cause the body to increase production of endorphins and upregulate the immune system;[5] it may also antagonize Toll-like receptor 4 that are found on macrophages, including microglia, possibly resulting in the reported anti-inflammatory effects.[4] Researchers have also examined "ultra-low-doses" of naltrexone at microgram, nanogram, and picogram doses, that are co-administered with opioid analgesics with the goal of increasing pain relief and reducing side effects.[4]
Research
Multiple studies have shown that low-dose naltrexone has promise as a treatment for chronic pain, some autoimmune disorders and cancers.[6][7][8] As of 2014, no peer-reviewed studies supporting low-dose naltrexone for multiple sclerosis (MS) have been published.[1] [5] Clinical trials for treatment of fibromyalgia were initiated in 2021.[9]
Prescription and medical formulations of low-dose naltrexone are not licensed or approved in the UK, EU and USA.
Low-dose naltrexone is also being studied in long COVID. However, efficacy has not been shown.[10][11]
In 2017, Raknes and Småbrekke published a drug utilization cohort study on Norwegian patient and prescriber characteristics, and dispense patterns, following a 2013 television documentary on low-dose naltrexone. They reported drawing upon the Norwegian Prescription Database and sales data not recorded in NorPD from the only Norwegian LDN manufacturer, with the caveat that these sources could not encompass the total. Their findings included that "Twenty percent of all doctors and 71% of general medicine practitioners registered in Norway in 2014 prescribed LDN at least once."[12]
Criticisms
Low-dose naltrexone advocates make numerous efficacy claims for myriad conditions, including those listed above, as well as; various types of cancer and immunocompromising conditions, Alzheimer's disease, HIV/AIDS, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, and Hashimoto’s thyroiditis.[citation needed]
As the UK's National Health Service noted in 2020, "...trials are necessary to draw firm conclusions on the efficacy of [low-dose naltrexone]."[5]
References
- ↑ 1.0 1.1 "Low-Dose Naltrexone". National MS Society. http://www.nationalmssociety.org/Treating-MS/Complementary-Alternative-Medicines/Low-Dose-Naltrexone.
- ↑ Parker, Claire E; Nguyen, Tran M; Segal, Dan; MacDonald, John K; Chande, Nilesh (1 April 2018). "Low dose naltrexone for induction of remission in Crohn's disease". Cochrane Database of Systematic Reviews 4 (4): CD010410. doi:10.1002/14651858.CD010410.pub3. PMID 29607497.
- ↑ 3.0 3.1 Niciu, Mark J.; Arias, Albert J. (24 July 2013). "Targeted Opioid Receptor Antagonists in the Treatment of Alcohol Use Disorders". CNS Drugs 27 (10): 777–787. doi:10.1007/s40263-013-0096-4. PMID 23881605.
- ↑ 4.0 4.1 4.2 Younger, J; Parkitny, L; McLain, D (April 2014). "The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain.". Clirheumatology 33 (4): 451–9. doi:10.1007/s10067-014-2517-2. PMID 24526250.
- ↑ 5.0 5.1 5.2 Eve, Marianne (5 February 2020). "What is the evidence for low dose naltrexone for treatment of multiple sclerosis?". Specialist Pharmacy Service. National Health Service. https://www.sps.nhs.uk/wp-content/uploads/2020/02/UKMI_QA_LDNfor-MS_Feb_2020.pdf.
- ↑ Kim, Phillip S; Fishman, Michael A (26 August 2020). "Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review". Current Pain and Headache Reports 24 (10): 64. doi:10.1007/s11916-020-00898-0. PMID 32845365. https://pubmed.ncbi.nlm.nih.gov/32845365.
- ↑ Younger, Jarred; Parkitny, Luke; McLain, David (April 2014). "The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain". Clinical Rheumatology 33 (4): 451–9. doi:10.1007/s10067-014-2517-2. PMID 24526250.
- ↑ Zijian Li; Yue You; Noreen Griffin; Juan Feng; Fengping Shan (August 2018). "Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy". International Immunopharmacology 61: 178–184. doi:10.1016/j.intimp.2018.05.020. PMID 29885638. https://pubmed.ncbi.nlm.nih.gov/29885638.
- ↑ Bruun, Karin Due; Amris, Kirstine; Vaegter, Henrik Bjarke; Blichfeldt-Eckhardt, Morten Rune; Holsgaard-Larsen, Anders; Christensen, Robin; Toft, Palle (December 2021). "Low-dose naltrexone for the treatment of fibromyalgia: protocol for a double-blind, randomized, placebo-controlled trial" (in en). Trials 22 (1): 804. doi:10.1186/s13063-021-05776-7. ISSN 1745-6215. PMID 34781989.
- ↑ Steenhuysen, Julie (18 October 2022). "Addiction drug shows promise lifting long COVID brain fog, fatigue". Reuters. https://www.reuters.com/business/healthcare-pharmaceuticals/addiction-drug-shows-promise-lifting-long-covid-brain-fog-fatigue-2022-10-18/.
- ↑ "Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study". Brain, Behavior, & Immunity - Health 24: 100485. October 2022. doi:10.1016/j.bbih.2022.100485. PMID 35814187.
- ↑ Raknes, G.; Småbrekke, L. (2016). "A sudden and unprecedented increase in low dose naltrexone (LDN) prescribing in Norway. Patient and prescriber characteristics, and dispense patterns. A drug utilization cohort study". Pharmacoepidemiology and Drug Safety 26 (2): 136–142. doi:10.1002/pds.4110. PMID 27670755.
- Wagner, George C; Masters, David B; Tomie, Arthure (1984). "Effects of phencyclidine, haloperidol, and naloxone on fixed-interval performance in rats". Psychopharmacology 84 (1): 32–38. doi:10.1007/BF00432020. PMID 6436887.
sv:Låg dos Naltrexon
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