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What is low dose naltrexone (LDN)?

Medically reviewed by Carmen Pope, BPharm. Last updated on Oct 17, 2024.

Official answer

by Drugs.com

What is low dose naltrexone?

Low dose naltrexone (LDN) means taking a dose of naltrexone that is up to one-tenth, or 10%, of the dose that is usually taken for opioid addiction. A low dose of naltrexone is approximately 4.5mg of naltrexone a day compared with the usual dosage of naltrexone for opioid addiction which is 50mg to 100mg a day.

Low dose naltrexone uses

Low dose naltrexone has been used to treat:

  • Autoimmune thyroid disorders
  • Cancer
  • Chronic fatigue syndrome
  • Chronic pain
  • Crohn’s disease
  • Fibromyalgia
  • Gulf War syndrome
  • Multiple sclerosis
  • Myalgic encephalomyelitis.

Using low dose naltrexone for these conditions is “off-label” (which means it hasn't been approved by the FDA but it is still a recognized use).

There actually haven't been many big trials at all investigating low dose naltrexone, but the benefits of low dose naltrexone became apparent when people on a tapering schedule of naltrexone reported improvement in pain and fatigue symptoms with lower dosages of naltrexone rather than higher dosages. Small trials have shown that low dose naltrexone is beneficial for some conditions such as fibromyalgia, Crohn's disease, and pain.

What should I avoid when taking low dose naltrexone?

Low dose naltrexone blocks opioid receptors and can precipitate opioid withdrawal, so it is important that you do not take any opioid (narcotic) pain relieving drugs at the same time as low dose naltrexone. You should not use low dose naltrexone treatment if you:

  • Are receiving opioid (narcotic) analgesics
  • Are addicted to opioids
  • Are withdrawing from opioids or have symptoms of opioid withdrawal
  • Have failed a naloxone challenge test or have a positive urine screen for opioids
  • Have acute hepatitis but may be allowed in patients with stable or compensated cirrhosis after considering the risks versus benefits
  • Are allergic to or have had a hypersensitivity reaction to naltrexone, polylactide-co-glycolide (PLG), or any other diluent or inactive ingredient in the product.

Tell your doctor or other health care provider of any recent use of opioids or any history of opioid dependence before starting low dose naltrexone to avoid having an opioid withdrawal. Your doctor may require that you pass a naloxone challenge test and/or a urine screen for opioids prior to low dose naltrexone use.

If you have been taking opioids of any kind, allow at least 7 days after your last dose of short-acting opioids or 10 to 14 days after your last dose of long-acting opioids to pass before starting low dose naltrexone.

If you are on opioids long term for conditions such as chronic fatigue and do not want to stop them, then you cannot take low dose naltrexone. Low dose tramadol (50mg two to three times daily) does not appear to cause problems with low dose naltrexone, according to some sources.

Low dose naltrexone should also be stopped at least 7 days before surgery.

What are the side effects of low dose naltrexone?

Side effects with low dose naltrexone are uncommon because the dose is so low and have been reported by less than 8% of people. Low dose naltrexone is unlikely to cause the same side effects as high dose naltrexone. Side effects of low dose naltrexone may include:

  • Difficulty sleeping (insomnia)
  • Nausea
  • Nightmares or wild dreams
  • Rarely, prolonged erections (priapism)
  • Rarely, weight loss.

Difficulty sleeping initially was reported by approximately 8% of people receiving low dose naltrexone but this resolved within two weeks in most people. Other side effects (such as nausea and wild dreams) were reported by less than 1% of people.

Low dose naltrexone is usually well tolerated with few side effects. Some people need a more gradual increase in their dosage to help them tolerate the drug. Low dose naltrexone should be started at an extremely low dose, such as 1 to 1.5mg/day, and the dosage should be increased by 1mg every week to a maximum of 4.5 mg/day.

What are the long term side effects of low dose naltrexone?

The long term side effects of low dose naltrexone are unknown because research has not investigated what happens to people who take the medication long term. However, naltrexone has a long history of safe use when used to treat opioid addiction.

What is the mechanism of low dose naltrexone?

Low dose naltrexone works in the opposite way to high dose naltrexone. This is called a paradoxical effect. At low dosages, naltrexone appears to “trick” the brain into producing more natural opioids (these are called endogenous opioids). It does this by binding briefly to opioid receptors, blocking our naturally occurring opioids from binding. Our body counteracts this by producing more naturally occurring opioids to "wash off" the low dose naltrexone. This increases the levels of naturally occurring opioids in our body which makes us feel good and provides pain relief.

Low dose naltrexone has a very short half-life – around 4 to 6 hours – which means its binding effects wear off quickly, but this is long enough to boost levels of naturally occurring opioids for 18 to 24 hours. Endogenous opioids are natural pain relievers and having more of these around in the body is one of the ways low dose naltrexone is thought to work.

Low dose naltrexone also appears to have anti-inflammatory effects by regulating microglial cells which have a key role in general and nerve inflammation. When microglial cells are activated, they produce pro-inflammatory cytokines, free radicals (reactive oxygen species), and nitric oxide – all of these substances have been associated with pain, inflammation, fatigue, feeling rundown or like you have come down with something. Low dose naltrexone is thought to stop microglial cells from being activated by blocking the TLR-4 receptor.

Low dose naltrexone is thought to relieve symptoms such as pain, fatigue, stress, and inflammation by increasing the production of endogenous opioids and dampening down the effect of microglial cells.

Related questions

How long does it take low dose naltrexone to work?

It may take up to 8 to 10 weeks for low dose naltrexone to work. It is important to keep taking it until at least then to know if it works for you.

What are the benefits of low dose naltrexone?

Most studies investigating low dose naltrexone have been small with most reporting a favorable effect for conditions such as fibromyalgia, Crohn's disease, and pain. Research has shown low dose naltrexone is safe, well tolerated, inexpensive, and has minimal side effects.

Low dose naltrexone for fibromyalgia

Two, separate small clinical trials investigated low dose naltrexone for fibromyalgia. A 28.8% reduction in baseline pain and a decrease in symptoms such as general satisfaction with life and improved mood (but not improved fatigue or sleep) was reported by 31 women in one trial. In the other trial, 10 women reported a 30% reduction in symptoms after 8 weeks of treatment with low dose naltrexone; those with a higher baseline erythrocyte sedimentation rate (a measure of underlying inflammation) reported the greatest response.

User reviews for low dose naltrexone has been mostly favorable with an average rating of 7.0 out of 10 from a total of 61 ratings for using low dose naltrexone for the off-label treatment of Fibromyalgia. 62% of reviewers reported a positive experience, while 25% reported a negative experience. Comments included "Naltrexone has been a Godsend for me", "I have Lupus, Fibromyalgia and severe arthritis in my neck. Naltrexone is the only drug that has worked", and "Naltrexone has changed my life in almost every way! Cured: fibromyalgia, rheumatoid arthritis, and Cushing disease! No more chronic pain".

Low dose naltrexone for Crohn’s disease

88% of people assigned low dose naltrexone (4.5mg/day) had at least a 70-point decline in the Crohn’s Disease Activity Index score (CDAI) after 12 weeks compared to 40% of placebo-treated patients (n=40). There was also a 5-point decline in the Crohn’s disease endoscopy index severity score in 78% of people taking low dose naltrexone compared with 28% taking placebo. Similar results were seen in an open-label prospective trial.

Low dose naltrexone for multiple sclerosis

A 17-week trial involving 96 patients with relapse-remitting or secondary progressive multiple sclerosis found health perception scores improved during the study although it did not reveal any significant difference in other symptoms such as pain, energy, emotional wellbeing, or overall quality of life.

Low dose naltrexone for other conditions

Small case series and other uncontrolled small trials have reported beneficial effects for low dose naltrexone for complex regional pain syndrome, diabetic painful neuropathy, chronic back pain, depression, autism, and cancer treatment, but more research is needed.

Does low dose naltrexone cause weight loss?

It is possible that low dose naltrexone may help with weight loss because lower dosages of naltrexone are thought to curb hunger and food cravings. Contrave is a long-acting tablet that contains 8mg of naltrexone and 90mg of bupropion that is FDA approved for weight loss in people who are overweight or obese with at least one weight-related condition such as high blood pressure or type 2 diabetes. In clinical trials, 36% to 48% of patients taking Contrave lost at least 5% of body weight. The dosage of naltrexone in Contrave is 8mg, which is higher than the amount typically used for low dose naltrexone but much less than the dose used for opioid withdrawal.

Weight gain is not a common side effect with low dose naltrexone treatment.

References
  • Younger, J., & Mackey, S. (2009). Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain medicine (Malden, Mass.), 10(4), 663–672. https://doi.org/10.1111/j.1526-4637.2009.00613.x
  • Parkitny L, Younger J. Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia. Biomedicines. 2017; 5(2):16. https://doi.org/10.3390/biomedicines5020016
  • Younger, J., Parkitny, L., & McLain, D. (2014). The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical rheumatology, 33(4), 451–459. https://doi.org/10.1007/s10067-014-2517-2
  • Bolton MJ, Chapman BP, Van Marwijk H. Low-dose naltrexone as a treatment for chronic fatigue syndrome BMJ Case Reports CP 2020;13:e232502.
  • What is Low Dose Naltrexone (LDN)? LDN Research Trust. https://ldnresearchtrust.org/what-is-low-dose-naltrexone-ldn
  • How low dose naltrexone helps treat autoimmune conditions. Barr center. https://barrcenter.com/how-low-dose-naltrexone-works-in-autoimmunity/#iLightbox[gallery12708]/0
  • Low Dose Naltrexone (LDN) – a review of evidence. Te Ora NZ. https://teora.co.nz/wp-content/uploads/2019/08/Low-Dose-Naltrexone-a-brief-review.pdf
  • Low Dose Naltrexone (LDN) Fibromyalgia and Chronic Fatigue Syndrome Resource Center Health Rising https://www.healthrising.org/treating-chronic-fatigue-syndrome/drugs/low-dose-naltrexone-ldn-fibromyalgia-chronic-fatigue-syndrom/
  • Younger J, Noor N, McCue R, Mackey S. Low-dose naltrexone for the treatment of fibromyalgia:
  • Findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis & Rheumatism 2013;65(2):529-538.
  • Smith, J. P., Bingaman, S. I., Ruggiero, F., Mauger, D. T., Mukherjee, A., McGovern, C. O., & Zagon, I. S. (2011). Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn's disease: a randomized placebo-controlled trial. Digestive diseases and sciences, 56(7), 2088–2097. https://doi.org/10.1007/s10620-011-1653-7
  • Smith, J. P., Stock, H., Bingaman, S., Mauger, D., Rogosnitzky, M., & Zagon, I. S. (2007). Low-dose naltrexone therapy improves active Crohn's disease. The American journal of gastroenterology, 102(4), 820–828. https://doi.org/10.1111/j.1572-0241.2007.01045.x
  • Sharafaddinzadeh, N., Moghtaderi, A., Kashipazha, D., Majdinasab, N., & Shalbafan, B. (2010). The effect of low-dose naltrexone on quality of life of patients with multiple sclerosis: a randomized placebo-controlled trial. Multiple sclerosis (Houndmills, Basingstoke, England), 16(8), 964–969. https://doi.org/10.1177/1352458510366857

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Does naltrexone cause weight gain?

Weight gain is not a common side effect with oral naltrexone treatment. When used in combination with bupropion, naltrexone is approved to help promote weight loss. Naltrexone is known to frequently cause stomach side effects like nausea and vomiting, stomach pain or cramping, and loss of appetite which could contribute to weight loss. Weight gain and increased appetite have been reported as a possible side effect, but is not common. Continue reading

Acamprosate vs naltrexone: How do they compare?

Acamprosate and naltrexone are two different medications that are used in the treatment of alcohol use disorder. They work in different ways to help people who are dependent on alcohol to abstain from drinking it. Naltrexone is also used for the treatment of opioid use disorder.

Acamprosate was thought to be slightly more effective at helping people with alcohol use disorder remain off alcohol, while naltrexone was thought to be slightly more effective at helping reduce heavy drinking and cravings, according to the results of a meta-analysis which used data from 64 trials.

Results from two small studies, however, indicate that naltrexone is more effective than acamprosate in a number of areas. Continue reading

How does naltrexone make you feel?

When taken as directed, naltrexone may reduce your cravings for alcohol or opioids. You’ll feel less of a need to take drugs or drink. Continue reading

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