Low-Dose Naltrexone: Can a Higher Dose Lead to Better Results?

Q: I have a question about low-dose naltrexone for chronic pain, I understand you use this in your clinic. The standard dose appears to be 4.5 mg in almost all of the information I can find. There are a few chronic pain MDs in the U.S. that seem to be using higher doses with success — a couple say to go up as high as 10 mg while another one is using it up to 4.5 mgs 3xday with great success for those who do not respond to one dose of 4.5 mgs. Do you have any thoughts on this? What I’ve read is that one should not give up on this medication if not getting benefits at 4.5 mgs. Thank you.

A: LDN, or low-dose naltrexone has recently become popular as a method to boost the immune system for a number of conditions, such as HIV, cancer, Crohn’s disease, multiple sclerosis, neurodegenerative disorders, chronic neuropathic pain, fibromyalgia, and other autoimmune diseases.

How Low-Dose Naltrexone Works

LDN works by temporarily blocking endorphins in the brain which causes a reciprocal boost in natural endorphins, and by down-regulating the inflammatory effect of immune cells called microglia in the brain that get turned on in certain situations. At a low dose, the side effects are minimal. Higher doses can cause sleep disturbances and may cause elevation of liver enzymes. Although I don’t usually go higher than 4.5 mg, most likely the doses you are talking about – 10-14 mg – are far from the 50 mg or higher dose that is used to block opioid overdose, and are therefore are probably safe. I don’t see any research on the efficacy of using higher doses, however.

Dr. Lisa Lilienfield


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