Have You Tried Low-Dose Naltrexone?

Patient Expert

There seems to be a subculture of patients who have tried low-dose naltrexone (LDN) to treat a variety of conditions from autoimmune diseases such as multiple sclerosis, to Alzheimer's disease, to HIV/AIDS and cancer.

Does it work?

Fans of the treatment say yes; but it's practically impossible to know because few double-blind clinical trials have taken place. How many people have tried LDN, for what disease, and with what outcomes? We don't know because these patients are rarely tracked, and some may not even tell their doctors they have used this drug off-label.

What is low-dose naltrexone (LDN)?

Naltrexone is a drug approved by the FDA for the treatment of opioid addiction. Opioids are medications that relieve pain. The typical dosage of naltrexone for opioid addiction is 50mg to 100mg daily.

LDN refers to daily dosages of naltrexone that are in the range of 3mg to 4.5mg. At this level, naltrexone has analgesic and anti-inflammatory properties not seen with larger doses and "may represent one of the first glial cell modulators to be used for the management of chronic pain disorders" (Younger, 2014).

Have studies explored LDN therapy and MS?

In three small studies, LDN was found to be safe and well tolerated in patients with MS. A 6-month phase 2 study in Italy also showed that spasticity levels were significantly improved in patients with PPMS (n=40) who took 5mg of LDN daily. Five participants dropped out of the trial and two participants experienced major adverse events. One participant experienced increased disability. Common side effects included urinary tract infections, mild agitation, sleep disturbance, and increased liver enzymes (Gironi, 2008).

In a 17-week randomized, double-blind, placebo-controlled, parallel-group, crossover study in persons with RRMS or SPMS (n=96), no statistical difference was seen in things such as pain, energy, emotional well-being, social, cognitive, and sexual functions, role limitations, health distress, and overall quality of life in patients taking LDN compared to those taking placebo (Sharafaddinzadeh, 2010). However, researchers note that health perception scores were statistically different between the groups throughout the trial and suggest a longer trial is needed to determine LDN's effect on quality of life for people with MS.

In an 8-week doubled-blind, placebo-controlled, crossover study, patients with MS taking 4.5mg LDN (n=80) reported significantly improved quality of life related to pain, mental health, and cognitive function (Cree, 2010). LDN had no impact on physical symptoms such as fatigue, visual function, or bowel, bladder, and sexual function. Unfortunately, complete data was only available for 60 of the original 80 participants due to dropouts and incomplete data which severely reduces the study's statistical power.

In a pilot study funded by the National MS Society, low-dose naltrexone, but not high-dose naltrexone, was found to be protective against the development of signs of neurological disease in a mouse model of MS called experimental autoimmune encephalomy (EAE) (Zagon, 2009). In a follow-up study in mice, low doses of naltrexone were found to halt progression of the MS-like disease, reverse neurological deficits, prevent the onset of neurological dysfunction over time (Rahn, 2011).

How might we examine LDN use in the broader MS community?

This is where a patient-powered research network such as iConquerMSâ„¢ may be able to help. If each person in the US who has ever tried LDN registers and shares their health data at iconquerMS.org, and those participants submit research questions related to LDN, scientists may be able to examine the data contributed by MS patients combined with data from millions of patients registered through the larger, national PCORnet to begin to look for deeper answers related to LDN's effectiveness for various conditions, including MS.

Please join me at iConquerMS to make research studies using Big Data a reality for MS patients!

See More Helpful Articles:


Cree BA, Komyeyeva E, Goodin DS. Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. Ann Neurol. 2010 Aug;68(2):145-50. doi: 10.1002/ana.22006.

Gironi M, Martinelli-Boneschi F, Sacerdote P, et al. A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis. Mult Scler. 2008 Sep;14(8):1076-83. doi: 10.1177/1352458508095828.

Rahn KA, McLaughlin PJ, Zagon IS. Prevention and diminished expression of experimental autoimmune encephalomyelitis by lowdose naltrexone (LDN) or opioid growth factor (OGF) for an extended period: Therapeutic implications for multiple sclerosis. Brain Res. 2011 Mar 24;1381:243-53. doi: 10.1016/j.brainres.2011.01.036. Epub 2011 Jan 20.

Sharafaddinzadeh N, Moghtaderi A, Kashipazha D, et al. The effect of low-dose naltrexone on quality of life of patients with multiple sclerosis: a randomized placebo-controlled trial. Mult Scler. 2010 Aug;16(8):964-9. doi: 10.1177/1352458510366857. Epub 2010 Jun 9.

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 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15.

Zagon IS, Rahn KA, Turel AP, McLaughlin PJ. Endogenous opioids regulate expression of experimental autoimmune encephalomyelitis: a new paradigm for the treatment of multiple sclerosis. Exp Biol Med (Maywood). 2009 Nov;234(11):1383-92. doi: 10.3181/0906-RM-189.