low-dose naltrexone
{{Short description|Off-label, experimental use of the drug}}
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{{More medical citations needed|date=January 2023}}
{{Use dmy dates|date=July 2021}}
Low-dose naltrexone (LDN) refers to daily naltrexone dosages that are roughly one-tenth of the standard opioid addiction treatment dosage. Most published research suggests a daily dosage of 4.5 mg, but this can vary by a few milligrams.{{cite journal | last1=Younger | first1=Jarred | last2=Parkitny | first2=Luke | last3=McLain | first3=David | title=The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain | journal=Clinical Rheumatology | publisher=Springer Science and Business Media LLC | volume=33 | issue=4 | date=2014-02-15 | issn=0770-3198 | doi=10.1007/s10067-014-2517-2 | pages=451–459| pmid=24526250 | pmc=3962576 }} Low-dose naltrexone has been studied for the treatment of multiple chronic pain disorders including fibromyalgia, multiple sclerosis, Crohn’s disease, and complex regional pain syndrome.{{cite journal | last1=Kim | first1=Phillip S. | last2=Fishman | first2=Michael A. | title=Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review | journal=Current Pain and Headache Reports | volume=24 | issue=10 | date=2020 | issn=1531-3433 | doi=10.1007/s11916-020-00898-0 | page=64| pmid=32845365 }}
Naltrexone is approved by the Food and Drug Administration (FDA) for medication-assisted treatment of alcoholism and opioid use disorders.{{cite journal | last=Sudakin | first=Daniel | title=Naltrexone: Not Just for Opioids Anymore | journal=Journal of Medical Toxicology | publisher=Springer Science and Business Media LLC | volume=12 | issue=1 | date=2015-11-06 | issn=1556-9039 | doi=10.1007/s13181-015-0512-x | pages=71–75| pmid=26546222 | pmc=4781804 }} Bernard Bihari's initial off-label usage of naltrexone in doses ranging from 1.5 mg to 3 mg as an adjuvant therapy for acquired immune deficiency syndrome (AIDS) in the 1980s led to the introduction of LDN into clinical practice.{{cite journal | last=Bihari | first=Bernard | title=Bernard Bihari, MD: low-dose naltrexone for normalizing immune system function | journal=Alternative Therapies in Health and Medicine | volume=19 | issue=2 | date=2013 | issn=1078-6791 | pmid=23594453 | pages=56–65}} Due to a lack of large-scale clinical trials and standardized research aimed at determining appropriate indications for LDN, it has remained an off-label option.{{cite journal | last1=Toljan | first1=Karlo | last2=Vrooman | first2=Bruce | title=Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization | journal=Medical Sciences | publisher=MDPI AG | volume=6 | issue=4 | date=2018-09-21 | issn=2076-3271 | doi=10.3390/medsci6040082 | doi-access=free | page=82| pmid=30248938 | pmc=6313374 }}
Mechanism of action
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.{{cite journal|last1=Niciu|first1=Mark J.|last2=Arias|first2=Albert J.|title=Targeted Opioid Receptor Antagonists in the Treatment of Alcohol Use Disorders|journal=CNS Drugs|date=24 July 2013|volume=27|issue=10|pages=777–787|doi=10.1007/s40263-013-0096-4|pmid=23881605|pmc=4600601}} 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). As Naltrexone is a competitive antagonist at the identical sites of action of many opioid agonists, such as morphine, care must be taken to ensure that Low-dose naltrexone is not taken near the same time as these medications, as they will not be as efficacious in relieving pain.{{Cite web |last=Papantoniou |first=E |date=2024-04-17 |title=What to Avoid When Taking Low Dose Naltrexone - Trinova Health |url=https://www.trinovahealth.com/what-to-avoid-low-dose-naltrexone/ |access-date=2025-02-17 |language=en-US}}
Research
Multiple studies have shown that low-dose naltrexone has promise as a treatment for chronic pain, some autoimmune disorders and cancers.{{cite journal|url=https://pubmed.ncbi.nlm.nih.gov/32845365|journal=Current Pain and Headache Reports|title=Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review|first1=Phillip S|last1=Kim|first2=Michael A|last2=Fishman|volume=24|edition=10|date=26 August 2020|issue=10|page=64|doi=10.1007/s11916-020-00898-0|pmid=32845365|s2cid=221310708|access-date=5 October 2021|archive-date=5 October 2021|archive-url=https://web.archive.org/web/20211005191937/https://pubmed.ncbi.nlm.nih.gov/32845365/|url-status=live}}{{cite journal|journal=Clinical Rheumatology|title=The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain|first1=Jarred|last1=Younger|first2=Luke|last2=Parkitny|first3=David|last3=McLain|volume=33|edition=4|pages=451–9|doi=10.1007/s10067-014-2517-2|pmid=24526250|pmc=3962576|date=April 2014|issue=4 }}{{cite journal|url=https://pubmed.ncbi.nlm.nih.gov/29885638|journal=International Immunopharmacology|title=Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy|author1=Zijian Li|author2=Yue You|author3=Noreen Griffin|author4=Juan Feng|author5=Fengping Shan|volume=61|pages=178–184|doi=10.1016/j.intimp.2018.05.020|pmid=29885638|date=August 2018|s2cid=47009754|access-date=5 October 2021|archive-date=5 October 2021|archive-url=https://web.archive.org/web/20211005191928/https://pubmed.ncbi.nlm.nih.gov/29885638/|url-status=live}}
As of 2014, no peer-reviewed studies supporting low-dose naltrexone for multiple sclerosis (MS) have been published.{{cite web|url=http://www.nationalmssociety.org/Treating-MS/Complementary-Alternative-Medicines/Low-Dose-Naltrexone|title=Low-Dose Naltrexone|work=National MS Society|access-date=9 January 2022|archive-date=27 January 2022|archive-url=https://web.archive.org/web/20220127190321/https://www.nationalmssociety.org/Treating-MS/Complementary-Alternative-Medicines/Low-Dose-Naltrexone|url-status=live}}{{cite web |last=Eve |first=Marianne |date=5 February 2020 |title=What is the evidence for low dose naltrexone for treatment of multiple sclerosis? |url=https://www.sps.nhs.uk/wp-content/uploads/2020/02/UKMI_QA_LDNfor-MS_Feb_2020.pdf |access-date=9 January 2022 |work=Specialist Pharmacy Service |publisher=National Health Service |archive-date=10 February 2022 |archive-url=https://web.archive.org/web/20220210010913/https://www.sps.nhs.uk/wp-content/uploads/2020/02/UKMI_QA_LDNfor-MS_Feb_2020.pdf |url-status=live }} Clinical trials for treatment of fibromyalgia were initiated in 2021.{{Cite journal |last1=Bruun |first1=Karin Due |last2=Amris |first2=Kirstine |last3=Vaegter |first3=Henrik Bjarke |last4=Blichfeldt-Eckhardt |first4=Morten Rune |last5=Holsgaard-Larsen |first5=Anders |last6=Christensen |first6=Robin |last7=Toft |first7=Palle |date=December 2021 |title=Low-dose naltrexone for the treatment of fibromyalgia: protocol for a double-blind, randomized, placebo-controlled trial |journal=Trials |language=en |volume=22 |issue=1 |pages=804 |doi=10.1186/s13063-021-05776-7 |issn=1745-6215 |pmc=8591911 |pmid=34781989 |doi-access=free }}
Low-dose naltrexone is also being studied in long COVID.{{cite news |url=https://www.reuters.com/business/healthcare-pharmaceuticals/addiction-drug-shows-promise-lifting-long-covid-brain-fog-fatigue-2022-10-18/ | title=Addiction drug shows promise lifting long COVID brain fog, fatigue | newspaper=Reuters | date=18 October 2022 | last1=Steenhuysen | first1=Julie | access-date=19 October 2022 | archive-date=19 October 2022 | archive-url=https://web.archive.org/web/20221019171516/https://www.reuters.com/business/healthcare-pharmaceuticals/addiction-drug-shows-promise-lifting-long-covid-brain-fog-fatigue-2022-10-18/ | url-status=live }}{{cite journal | vauthors = O'Kelly B, Vidal L, McHugh T, Woo J, Avramovic G, Lambert JS | title = Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study | journal = Brain, Behavior, & Immunity — Health | volume = 24 | pages = 100485 | date = October 2022 | pmid = 35814187 | pmc = 9250701 | doi = 10.1016/j.bbih.2022.100485 }}
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]."{{cite journal |last1=Toljan |first1=Karlo |last2=Vrooman |first2=Bruce |year=2018 |title=Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization |journal=Medical Sciences |volume=6 |issue=4 |pages=82 |doi=10.3390/medsci6040082 |doi-access=free |pmc=6313374 |pmid=30248938}} The UK’s National Health Service echoed this sentiment in 2020.
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 further research is needed.{{cite journal |last1=Aitcheson |first1=Nicholas |last2=Lin |first2=Zhen |last3=Tynan |first3=Kristin |year=2023 |title=Low-dose naltrexone in the treatment of fibromyalgia: A systematic review and narrative synthesis |journal=Australian Journal of General Practice |publisher=Royal Australian College of General Practitioners |volume=52 |issue=4 |pages=189–195 |doi=10.31128/AJGP-09-22-6564 |doi-access=free|pmid=37021443 }}
References
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{{Opioidergics}}
{{DEFAULTSORT:Low Dose Naltrexone}}