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Prescription medicine / off-label wellness

Naltrexone

Prepared by the ezGLP team. Sources last checked . Profile reviewed .

Also known as Low-dose naltrexone, LDN

Routes represented in the knowledgebase: Oral / Subcutaneous (SubQ).

Educational overview

Approved for alcohol and opioid use disorders; low-dose use for pain or inflammation is off-label. It blocks opioid analgesia and can precipitate withdrawal.

Naltrexone is a competitive antagonist at opioid receptors, with greatest affinity for the mu receptor and further activity at kappa and delta sites. Structurally it is a derivative of oxymorphone, but unlike an agonist it occupies the receptor without producing opioid effects, blocking both exogenous opioids and endogenous endorphins. In alcohol use disorder its benefit is attributed to blunting the opioid-mediated reward signalling that follows drinking. The parent molecule has a plasma half-life of a few hours while the active metabolite 6-beta-naltrexol persists longer, and receptor blockade outlasts plasma concentrations, which is what allows once-daily oral or monthly injectable administration.

Evidence for the approved indications is substantial. In alcohol use disorder, the COMBINE trial published in JAMA in 2006 randomised 1383 adults and reported better drinking outcomes with naltrexone plus medical management than with placebo, while acamprosate did not separate from placebo. In opioid use disorder, trials of the extended-release injectable form given after detoxification reported less relapse than placebo and outcomes comparable to buprenorphine-naloxone among participants who managed to start treatment. Evidence for low-dose naltrexone is far thinner: systematic reviews covering fibromyalgia, chronic pain and long COVID describe small, frequently unblinded studies with heterogeneous outcomes and conclude that adequately powered trials are still absent.

The FDA approved oral naltrexone for opioid dependence in 1984 and for alcohol dependence in 1994, then approved the extended-release intramuscular suspension Vivitrol for alcohol dependence in 2006 and for prevention of relapse to opioid dependence following detoxification in 2010; other national regulators have authorised equivalent products. A hepatotoxicity boxed warning once carried by oral naltrexone was removed in 2013 after review of accumulated data. Labels still warn about precipitated withdrawal in anyone with opioids in their system, reduced opioid tolerance after a period of blockade, and interference with opioid analgesia. Low-dose naltrexone is not an approved product anywhere and is compounded off-label.

Oral tablets are held at controlled room temperature under the manufacturer's label, while the extended-release injectable suspension is refrigerated, has a limited window out of refrigeration before administration, and is supplied as a kit with its own diluent and needles. Compounded low-dose capsules or liquids instead carry the dispensing pharmacy's beyond-use date and a strength chosen for the individual prescription, which can differ from a commercial tablet by an order of magnitude. Recording formulation, strength, route, manufacturer or pharmacy and lot number in an inventory record is what keeps a dose log unambiguous across such different presentations.

Category
Prescription medicine / off-label wellness
Routes represented
Oral / Subcutaneous (SubQ)
Storage context
Follow the product or pharmacy label; requirements vary by route and formulation.
Authoritative overview

Published literature

No verified PubMed or DOI link is available for this entry.

Safety evidence

Common or reported: nausea, headache, dizziness, fatigue, insomnia, vomiting, anxiety, sleepiness.

Serious or important: precipitated opioid withdrawal, liver injury, blocked opioid analgesia.

Safety evidence source

Interaction evidence

These are general, pairwise evidence notes. Green identifies the potential-synergy category, while Lv3/Lv2/Lv1 communicates evidence strength; it does not guarantee benefit or cancel a safety warning.

With opioids

Safety flag

Naltrexone can precipitate severe withdrawal, block analgesia, and prompt dangerous attempts to overcome opioid blockade.

Interaction evidence source

With PT-141

Safety flag

Bremelanotide substantially decreases oral naltrexone exposure and can cause treatment failure.

Interaction evidence source

Common questions

What is naltrexone approved for?

Its approved indications are alcohol use disorder and opioid use disorder. Oral tablets are approved for alcohol dependence and for blockade of exogenous opioids, and the extended-release intramuscular suspension is approved for alcohol dependence and for prevention of relapse to opioid dependence after detoxification. Naltrexone also appears as one component of an approved fixed-dose combination with bupropion for chronic weight management.

What is low-dose naltrexone (LDN) and is it proven?

Low-dose naltrexone describes compounded strengths far below those in approved products, prescribed off-label for conditions including fibromyalgia, Crohn's disease, multiple sclerosis and long COVID. No regulator has approved it for any indication. Systematic reviews published between 2020 and 2026 found mostly small studies, limited blinding and inconsistent outcome measures, and concluded that the evidence remains preliminary rather than established.

Does naltrexone block pain medication?

Yes, for opioid analgesics. Because naltrexone occupies opioid receptors, labels state that opioid-containing medicines will not produce their usual analgesic effect during blockade, and that attempts to overcome the blockade with large opioid amounts risk fatal overdose. Labels also describe reduced opioid tolerance after a period of treatment. Non-opioid analgesics are unaffected by the receptor blockade.

What is the difference between oral naltrexone and Vivitrol?

Both deliver naltrexone, but the route and duration differ. Oral tablets are taken daily and depend on continued adherence, whereas Vivitrol is an extended-release suspension given as a gluteal intramuscular injection about once a month by a health professional, producing sustained blockade between visits. Vivitrol carries additional labelled warnings about injection-site reactions, including necrosis in rare cases.

Is naltrexone the same as naloxone?

No, although both are opioid antagonists with similar names. Naloxone acts within minutes and is short-acting, which suits emergency reversal of opioid overdose, and it is poorly absorbed by mouth. Naltrexone is orally active with a much longer duration of receptor blockade, which suits maintenance treatment of alcohol and opioid use disorder rather than acute reversal.

Further reading

Summarised from published literature for reference only, with citations to the source. Evidence is graded as reported and is not a recommendation to combine, dose, or use any compound.

For personal tracking and education only. Not medical advice, diagnosis, or treatment, and not a medical device. Peptides may be prescription-only or unapproved where you live. Consult a licensed healthcare professional.