Low-dose naltrexone describes the

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...

, experimental use of the medication

naltrexone Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been foun ...

at low doses for diseases such as Crohn's disease and multiple sclerosis. Naltrexone is typically prescribed for

opioid dependence Opioid use disorder (OUD) is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. Op ...

or alcohol dependence, as it is a strong opioid antagonist. It has been suggested 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. Anecdotal reports have suggested that low-dose naltrexone may be effective in treating a wide range of diseases, including

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

, chronic

Lyme Disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the ''Borrelia'' bacterium, which is spread by ticks in the genus ''Ixodes''. The most common sign of infection is an expanding red rash, known as erythema migran ...

, chronic fatigue syndrome

HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...

, fibromyalgia patients, arthritis, and immunity for immunosuppressed patients. Its use is increasing due to its anti-inflammatory properties and minimal

side effects In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

. LDN's mechanism of action (if any) is still incompletely understood.

Mechanism of action

Action of naltrexone at normal dose

Naltrexone Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been foun ...

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 receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous lig ...

s. Standard therapeutic doses of naltrexone block these receptors, which does two things; it prevents inhibition of

GABA receptor The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and ...

s (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).

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. 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; it may also antagonize

Toll-like receptor 4 Toll-like receptor 4 is a protein that in humans is encoded by the ''TLR4'' gene. TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. Its activation leads to an ...

that are found on

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

, including microglia, possibly resulting in the reported anti-inflammatory effects. Researchers have also examined "ultra-low-doses" of naltrexone at microgram, nanogram, and picogram doses, that are co-administered with

opioid analgesic Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid u ...

s with the goal of increasing pain relief and reducing side effects.

Research

Multiple studies have been claimed to show that low-dose naltrexone has promise as a treatment for chronic pain, some autoimmune disorders and cancers. More research is needed. As of 2014 no peer-reviewed studies that would justify clinical use of low-dose naltrexone in treating multiple sclerosis (MS) have been published. Prescription and medical formulation of low-dose naltrexone in the UK are unlicensed in the treatment of multiple sclerosis. Clinical trials for treatment of fibromyalgia were initiated in 2021. Its use in

Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid may enlarg ...

is promising for those patients. In 2022, a handful of studies have begun experimenting the safety of using the drug for treatment of

Long COVID Long COVID or long-haul COVID (also known as post-COVID-19 syndrome, post-COVID-19 condition, post-acute sequelae of COVID-19 (PASC), or chronic COVID syndrome (CCS)) is a condition characterized by long-term health problems persisting or app ...

, although efficacy has not been shown. 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." Between March 2008 and November 2022,

PubMed Central PubMed Central (PMC) is a free digital repository that archives open access full-text scholarly articles that have been published in biomedical and life sciences journals. As one of the major research databases developed by the National Center fo ...

of the

United States National Library of Medicine The United States National Library of Medicine (NLM), operated by the United States federal government, is the world's largest medical library. Located in Bethesda, Maryland, the NLM is an institute within the National Institutes of Health. Its ...

listed 68 open-access full-text articles published on low-dose naltexone by article title alone, among a total of 8408 by all search-fields beginning 1975 (not counting restricted-access publications). Across roughly the same time-span,

Europe PubMed Central Europe PubMed Central (Europe PMC) is an open-access repository which contains millions of biomedical research works. It was known as UK PubMed Central until 1 November 2012. Service Europe PMC provides free access to more than 3.7 million full-te ...

(including Canada 2018 onward) listed 6,425 by all search-fields.http://europepmc.org/search?query=low%20dose%20naltrexone (These and other databases include duplicated listings as a result of cooperation across the PubMed Central International network.) Th
LDN Research Trust
was founded in 2004 as a nonprofit charity in the U.K. with a mission to raise funds for clinical trials of LDN, increase awareness of LDN's potential as a treatment, and promote patient access.

Criticisms

In addition to proposed uses for low-dose naltrexone that have been studied in clinical research, low-dose naltrexone advocates make claims of its efficacy in treating other conditions, including: various types of cancer, Alzheimer's disease,

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...

, fibromyalgia, chronic fatigue, Hashimoto’s, and immunocompromised patients. More research is needed: however, as the UK's

National Health Service The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...

noted in 2020, "...trials are necessary to draw firm conclusions on the efficacy of ow-dose naltrexone.. However, there is little incentive for pharmaceutical companies to conduct this research as naltrexone is inexpensive and off-patent."

References

{{DEFAULTSORT:Low Dose Naltrexone Opioid receptors sv:Låg dos Naltrexon