Low-Dose Naltrexone (LDN)

About Naltrexone

Naltrexone blocks opioid docking sites on cells and is used in clinical practice in people trying to rid themselves of addiction to opiates.
Low dose naltrexone (LDN) refers to the use of naltrexone in doses approximately one-tenth those used for drug/alcohol rehabilitation purposes. LDN is one of the more contentious but promising new potential therapies for MS.
The first formal clinical research into the effect of LDN on immune diseases took place at Penn State University's Hershey Medical Center. This was looking at its effect on people with Crohn's Disease, an inflammatory disease of the digestive tract. In the open label study, 17 people took LDN daily in addition to their other medication. All bar two of the participants exhibited a response to therapy. The treatment was well tolerated with the most common side effect being sleep disturbances, which affected seven participants. (1)

Trials of LDN in MS

A pilot study of low dose naltrexone therapy in multiple sclerosis was run by the Milan neurological researcher, Dr. Maira Gironi and colleagues. The Italian pilot study involved 40 people with primary progressive MS. Participants received 4mg of LDN for six months, with researchers looking primarily at safety but also at the effect on spasticity, pain, fatigue, depression, and quality of life.
The results were published in September 2008 and showed LDN was safe and well-tolerated. There was a significant reduction of spasticity during the trial, but half the participants reported an increase in pain. There were no significant changes to measures of fatigue, depression or quality of life during the trial (2)
More recently a pilot clinical study, by Bruce Cree, MD, Douglas Goodin, MD, and co-researchers at the Multiple Sclerosis Center at UCSF, published a “Pilot Trial 0f Low Dose Naltrexone and Quality of Life in MS” The trial which was presented at the 2008 American Academy of Neurology, suggested that LDN may improve several measures of mental health quality of life and pain, and that further testing in larger numbers of individuals may be warranted (3)
The clinical trial initially involved 80 people with all types of multiple sclerosis; however the finished trial only had complete data on 60 of the original participants as a result of drop outs and incomplete data. All participants received both the LDN for eight weeks and inactive dummy pills (placebo) for eight weeks in a study design known as “crossover,” with one week free of treatment in between. Some received the LDN during the first eight-week period and some during the second eight-week period. Participants were given a Web-based battery of quality of life tests called the MS Quality of Life Inventory (MSQLI) before the first treatment period and after each study period. The MSQLI asks the individual to report on mental and physical aspects of their condition including mental health, pain, perceived cognitive deficits, fatigue, and visual, bladder and bowel symptoms and sexual satisfaction.
The investigators found that LDN significantly improved quality of life (specifically, mental health, pain, and self-reported cognitive function), but no impact was observed on aspects of physical quality of life (such as fatigue, bowel and bladder control, sexual satisfaction, and visual function). Vivid dreaming was reported during the first week of treatment by some patients, but no other adverse effects were reported. The investigators emphasized that the results did not support the use of LDN instead of proven MS treatments.


Bruce Cree and his co-researchers concluded that during this exploratory, single center study, 8 weeks of treatment LDN was associated with symptomatic benefit with respect to mental health, pain and perceived cognitive deficits in MS. Confirmation of these findings in a multi center trial will be necessary to make definite conclusions about the possible symptomatic benefit of LDN in MS. The researchers conclude that a longer duration of treatment is necessary to determine whether LDN has any benefit with respect to physical outcome measures.
Based on some published laboratory studies, the investigators cite the possibility that LDN increases levels of endorphins in the brain, which are the body’s natural pain relievers. As such, immunological and endorphin studies may help elucidate the mechanism of action of LDN.
Because LDN stimulates the immune system, it should not be taken by people also taking one of the beta interferon drugs or other drugs that suppress the immune system. The full strength drug should not be used in conjunction with an opioid containing medication or with people with hepatitis or liver problems. The low dose treatment is not associated with significant side effects.

Further Info

Further updates and information about LDN can be found on the website which gives periodic updates on progress. There is also a gateway website where you will find many links to worldwide information, resources and events:


(1) Smith JP, Stock H, Bingaman S, et al.
Low-dose naltrexone therapy improves active Crohn's Disease.
American Journal of Gastroenterology 2007;102:1-9.

(2) Gironi M, Martinelli-Boneschi F, Sacerdote P, et al.
A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis.
Multiple Sclerosis 2008;14(8):1076-1083.

(3) Pilot trial of low dose naltrexone and quality of life in MS
Bruce A.C. Cree, Elena Kornyeyeva, Douglas S. Goodin
Multiple Sclerosis Center at UCSF.