Low-Dose Naltrexone: A Future Gold Medalist?

Lilian White, MD
Posted on August 12, 2024

Naltrexone is FDA-approved for treating alcohol use disorder. More recently, low doses (e.g., 4.5 mg) of naltrexone are being studied for use in a wide variety of disorders. Typical doses of naltrexone (i.e., 50 mg) are thought to work primarily through antagonism of the opioid receptor, reducing cravings for alcohol in those with the disorder; however, at lower doses, the mechanism of action of naltrexone appears to be more nuanced.

Low-dose naltrexone has been found to upregulate endogenous opioid production, perhaps explaining part of the mechanism by which it reduces central pain in patients. Many chronic conditions have immunomodulation and relief of neuroinflammation at the core of their pathophysiology, making low-dose naltrexone a medication with many potential applications. Currently, it has been studied for use in fibromyalgia, post-COVID syndrome, postural orthostatic tachycardia syndrome (POTS), Crohn’s disease, chronic pain, multiple sclerosis, inflammatory skin disorders, and others.

Perhaps the most evidence to date for off-label use of low-dose naltrexone is fibromyalgia, as noted by Dr. Manasa Irwin in a recent AFP letter to the editor. As many as one-third of patients with fibromyalgia experience significant disability, much of which is due to pain. Low-dose naltrexone reduces pain and improves sleep, fatigue, and cognitive symptoms in patients with fibromyalgia, making it a promising treatment option. In patients with Crohn’s disease, low-dose naltrexone improves quality of life and promotes disease remission. Low-dose naltrexone likewise improves mental health–related quality of life and disability in patients with multiple sclerosis.

Low-dose naltrexone is relatively safe and generally well tolerated. Possible adverse effects include headache, vivid dreams, and gastrointestinal upset and/or diarrhea. Headaches may be mitigated by reducing the dose or titrating up the dose more gradually. Vivid dreams can sometimes be mitigated by dosing the medication in the morning.

The use of low-dose naltrexone is somewhat limited by the necessity of requiring a compounding pharmacy for dispensing; lack of insurance coverage may also limit its use. However, naltrexone itself is inexpensive, and out-of-pocket costs for compounding low-dose naltrexone tend to be less than $100 per month. Dosing of the medication may vary by patient tolerability and the medical condition being treated. A typical dosing schedule is 1.5 mg for 1 week, increasing by 1.5 mg each week to a goal dose of 4.5 mg daily. 

Overall, low-dose naltrexone appears to be a well-tolerated medication with a broad array of possible applications for patient care. Anecdotally, I’ve had some patients with post-COVID syndrome, POTS, and fibromyalgia experience significant benefits. One patient in particular had significant orthostatic symptoms with post-COVID syndrome. He used to enjoy practicing taekwondo but was unable to participate due to his symptoms. After a couple of months of taking low-dose naltrexone, he arrived at the office with a smile: Not only was he enjoying practicing taekwondo again, but he had also begun training to become a teacher.

Of course, no medication is a panacea. The generic, off-patent status of naltrexone makes it unlikely there will be any large randomized controlled trials. Low-dose naltrexone is a promising treatment option, and we still have much to learn about these new applications of an older medication.