Low-Dose Naltrexone (LDN): What It Is and How It's Being Studied

Low-dose naltrexone, usually shortened to LDN, has a loyal following online. The research is early. The two pilot trials cited most often enrolled 10 and 80 people.

What is LDN?

Naltrexone is a prescription medication that blocks opioid receptors. At its standard strength, it has been used for decades in addiction medicine.

"Low-dose" naltrexone refers to taking naltrexone at a small fraction of that standard strength. Researchers have proposed that, at these much lower amounts, naltrexone acts differently in the body than it does at full strength. Your physician sets the strength and schedule if LDN is prescribed.

How researchers think LDN works

There are two main theories, both described in a 2018 review in Medical Sciences (Toljan and Vrooman):

Short opioid-receptor blockade. A brief block of opioid receptors may prompt the body to increase its own opioid signaling afterward.

Effects on glial cells. Naltrexone may also act on immune cells in the brain and spinal cord, called glia, through a receptor known as TLR4. A 2014 review in Clinical Rheumatology (Younger, Parkitny, and McLain) describes this glial pathway and notes that it appears separate from naltrexone's better-known opioid effects.

Both are working theories. Neither has been fully confirmed in people.

What studies have measured

Most LDN studies are small pilot trials. Here are two that are often cited.

A fibromyalgia pilot (2009). Younger and Mackey enrolled 10 women with fibromyalgia in a single-blind crossover study published in Pain Medicine. Participants reported lower daily symptom scores during the LDN phase than during the placebo phase. Side effects, including insomnia and vivid dreams, were described as rare, minor, and short-lived. Ten participants is a very small group, and the authors called for larger trials. Individual results vary.

A multiple sclerosis quality-of-life pilot (2010). Cree and colleagues ran an 8-week, double-masked, placebo-controlled crossover trial published in Annals of Neurology. Eighty people enrolled and 60 completed it. Participants reported small improvements on several mental-health quality-of-life questionnaires. LDN was well tolerated, and no serious adverse events occurred. The authors noted that dropouts and data errors reduced the study's statistical power. Individual results vary.

The 2014 review by Younger and colleagues summed up the field this way: LDN use for chronic conditions is still highly experimental, published trials are small, and few results have been replicated.

What the research has not shown

LDN has not been proven to work for any specific condition in large, well-controlled trials. The studies above measured symptoms and questionnaire scores in small groups. They did not establish LDN as a therapy for fibromyalgia, multiple sclerosis, or any other disease. If you are managing a diagnosed condition, keep working with the clinician who manages it.

LDN at NUVARA

LDN (Low-Dose Naltrexone) is available as capsules after physician review. Compounded medication. Not FDA-approved.

Compounding is how LDN is usually supplied, because standard naltrexone tablets come in a much higher strength. Compounded medications are prepared for one patient from a prescription, and the FDA does not review them for safety, effectiveness, or quality before they are dispensed.

Common side effects

Side effects reported with LDN include:

• Vivid dreams
• Trouble sleeping
• Headache
• Nausea
• Feeling tired or on edge in the first weeks

Tell your physician if a side effect does not settle. Get medical care right away for signs of an allergic reaction, such as swelling of the face or throat, hives, or trouble breathing.

Who LDN is not for

LDN may not be appropriate if you:

• Take any opioid medication, including prescription pain relievers, some cough medicines, or medication for opioid use disorder. Naltrexone blocks opioids and can cause sudden withdrawal.
• Expect surgery or a procedure that may need opioid pain control. Tell your surgeon and anesthesia team that you take naltrexone.
• Have liver disease or hepatitis
• Are pregnant, trying to become pregnant, or breastfeeding
• Have had an allergic reaction to naltrexone
• Are under 18

Bring a full list of your medications and supplements to your intake.

How ordering works at NUVARA

Start online from home. A U.S.-licensed physician reviews your intake, usually within 24 hours. Your first visit includes a brief live telehealth call to establish care, and refills are usually reviewed online.

If your physician prescribes LDN, the prescription is prepared by one of our US-based partner pharmacies, a state-licensed 503A compounding pharmacy, and shipped to you. NUVARA is not a pharmacy and does not prepare medications. A prescription is required and approval is not guaranteed. Your card is authorized when you order and charged only if the physician approves. If not, the hold is released.

See the LDN page. Compounded medication. Not FDA-approved.

Frequently asked questions

What is LDN?

LDN stands for low-dose naltrexone: the prescription medication naltrexone, taken at a small fraction of its standard strength.

What is low-dose naltrexone used for?

LDN is being studied in small trials for conditions involving chronic pain and immune activity. It has not been proven to work for any specific condition. Physicians may prescribe it off-label after reviewing your history.

What are low-dose naltrexone side effects?

The most commonly reported side effects are vivid dreams and trouble sleeping. Headache and nausea have also been reported.

Can I take LDN with opioid pain medication?

No. Naltrexone blocks opioids and can trigger withdrawal. Tell your physician about any opioid use before starting.

What is the FDA status of LDN?

LDN at NUVARA is a compounded medication. Not FDA-approved. Consult with your MyNuvara Health physician about whether it fits your health history.

References

1. Toljan K, Vrooman B. Low-dose naltrexone (LDN): review of therapeutic utilization. Med Sci (Basel). 2018;6(4):82. PubMed 30248938 · doi:10.3390/medsci6040082
2. Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014;33(4):451-459. PubMed 24526250 · doi:10.1007/s10067-014-2517-2
3. Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. 2009;10(4):663-672. PubMed 19453963 · doi:10.1111/j.1526-4637.2009.00613.x
4. Cree BA, Kornyeyeva E, Goodin DS. Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. Ann Neurol. 2010;68(2):145-150. PubMed 20695007 · doi:10.1002/ana.22006

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Medical disclaimer: This article is for general education only and is not medical advice. It does not replace an evaluation by a licensed clinician. Talk with your MyNuvara Health physician before starting, stopping, or changing any medication. If you think you are having a medical emergency, call 911.