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 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 suggested that LDN might operate as an anti-inflammatory agent and therefore be used to treat some chronic conditions such as chronic pain, but the research is still highly experimental and few studies have been replicated.[3]

Some proponents of low-dose naltrexone have brought forth unproven[2] claims about its efficacy in treating a wide range of diseases, including cancer, chronic fatigue syndrome and HIV/AIDS.

Mechanism of action

Action of naltrexone

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.[4] Standard therapeutic doses of naltrexone blocks these receptors, which does two things; it prevents inhibition of GABA receptors (normally, signalling 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).[4]

Hypothesised action of LDN

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.[3] It is hypothesised that 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, and any reported anti-inflammatory effects might be due to that.[3][6]

These apparent effects have not been seen at standard doses or in major trials.[3] 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.[3]

Research

Organizations promoting low-dose naltrexone have advocated it as a treatment for a variety of medical conditions,[7] but research has not demonstrated its effectiveness.[2]

No peer-reviewed studies that would justify clinical use of low-dose naltrexone in treating multiple sclerosis (MS) have been published.[1] As of 2015 the UK National Health Service had concluded that it could not be recommended for treating the symptoms of multiple sclerosis due a lack of evidence. Prescription and medical formulation of low-dose naltrexone in the UK are unlicensed in the treatment of multiple sclerosis.[5]

Criticisms

In addition to proposed uses for low-dose naltrexone that have been studied in clinical research, low-dose naltrexone advocates make unproven claims of its efficacy in treating other conditions, including: various types of cancer, Alzheimer's disease, HIV/AIDS, rheumatoid arthritis, and others. Steven Novella of the Yale University School of Medicine disputed these claims as unsupported by rigorous clinical research, calling many applications pseudoscientific.[2]

References
  1. "Low-Dose Naltrexone". National MS Society. Retrieved 12 May 2014.
  2. Novella, Steven (5 May 2010). "Low Dose Naltrexone – Bogus or Cutting Edge Science?". Retrieved 5 July 2011.
  3. 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. PMC 3962576. PMID 24526250.
  4. 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. PMC 4600601. PMID 23881605.
  5. Smith, Katie (6 November 2015). "What is the evidence for low dose naltrexone for treatment of multiple sclerosis?". Specialist Pharmacy Service, National Health Service. Retrieved 12 November 2016.
  6. Ngian GS, Guymer EK, Littlejohn GO (February 2011). "The use of opioids in fibromyalgia". Int J Rheum Dis. 14 (1): 6–11. doi:10.1111/j.1756-185X.2010.01567.x. PMID 21303476.
  7. Bowling, Allen C. "Low-dose naltrexone (LDN) The "411" on LDN". National Multiple Sclerosis Society. pp. 44–46. Archived from the original on 29 September 2009. Retrieved 14 May 2014.

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