Low-dose naltrexone (LDN) describes the off-label 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.
Naltrexone is typically prescribed for opioid dependence or alcohol dependence, as it is a strong opioid antagonist. Preliminary research has been promising for use of LDN in treating chronic medical conditions such as chronic pain, but at this stage the use of LDN as a treatment is still experimental and more research needs to be done before it can be widely recommended.
Some proponents of low-dose naltrexone have brought forth unproven claims about its efficacy in treating a wide range of diseases, including cancer and HIV/AIDS. Low-dose naltrexone organizations have promoted its use on their webpages.
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. 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).
Low-dose naltrexone refers to doses at about 1/10th the size of the dose used normally. One hypothesis behind low-dose naltrexone's mechanism of action is that inhibiting opioid receptors at low doses might cause the body to increase production of endorphins and upregulate the immune system; 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. These apparent effects have not been seen at standard doses or in major trials. 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.
Organizations promoting low-dose naltrexone have advocated it as a treatment for a variety of medical conditions. However, currently no peer-reviewed studies that would justify clinical use of low-dose naltrexone in treating multiple sclerosis (MS) have been published.
Low-dose naltrexone may relieve certain symptoms in people with multiple sclerosis, although medical practitioners often advise against using it as a substitute to proven therapies, and the evidence supporting its use in MS is not robust, as different studies have come to conflicting conclusions. 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.
Although preliminary studies have been published on Crohn's disease, the small size and preliminary nature of the studies prevent drawing "any firm conclusions regarding the efficacy and safety of LDN used to treat patients with active Crohn's disease."[needs update]
One small pilot study found a reduction in fibromyalgia symptoms in patients treated with low-dose naltrexone.
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. He further argues that the claim that low-dose naltrexone as an effective treatment for both immune dysfunction and autoimmune diseases is contradictory, as increasing activity of the immune system could make the autoimmune disease, in which overstimulation of the immune system causes the system to attack the host, worse.
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