Low-Dose Naltrexone Side Effects: Incidence Rates Across Trials

Where LDN side-effect rates come from

LDN is naltrexone at 0.5 to 6 mg a day, most often 4.5 mg, used off-label and made mainly by compounding pharmacies. FDA says compounded drugs are not FDA-approved and that it does not verify their safety, effectiveness or quality before marketing [4][6].

A 2026 review screened 105 studies and found 15 randomized trials, with most other evidence being case reports, case series and observational studies. Because most LDN studies are small, rates for less common effects are uncertain [4].

What the trials show

The 2024 meta-analysis of four randomized fibromyalgia trials (222 patients) found a higher incidence of vivid dreams and nausea with LDN than placebo, and no significant difference in serious adverse events [3].

In the 12-month INNOVA trial of 98 women, 68.8% on LDN 4.5 mg reported an adverse event versus 72% on placebo. Events were predominantly mild and transient, and no treatment-related serious events occurred [5]. A 2013 crossover trial of 31 women rated LDN equally tolerable as placebo, with no serious side effects reported [7].

The 2026 review describes LDN as generally safe and well tolerated, and lists insomnia, vivid dreams, nausea and dizziness as the effects most often reported [4].

The 50 mg tablet figures, for contrast

In an open-label study of about 570 people with alcoholism taking 50 mg tablets, new-onset reactions in 2% or more were nausea 10%, headache 7%, dizziness 4%, nervousness 4%, fatigue 4%, insomnia 3%, vomiting 3%, anxiety 2% and somnolence 2% [1]. In two placebo-controlled 12-week alcohol trials with 93 patients on 50 mg daily, five stopped because of nausea [1]. The tablet label says naltrexone has not been shown to cause significant increases in complaints in placebo-controlled trials in patients known to be opioid-free for more than 7 to 10 days [1].

What the labels list as serious

The labels list as contraindications receiving opioid analgesics, being currently dependent on opioids (including methadone or buprenorphine), acute opioid withdrawal, a failed naloxone challenge or positive urine screen for opioids, and a history of hypersensitivity to naltrexone or the product's components [1][2].

The tablet label says precipitated withdrawal can be severe: symptoms usually appeared within five minutes and lasted up to 48 hours, with mental status changes and fluid losses requiring intravenous fluids, and postmarketing cases needing hospital admission and sometimes intensive care [1]. After treatment ends, at the end of a dosing interval or after a missed dose, opioid tolerance is lower and fatal overdoses have been reported; both labels advise strongly considering an opioid overdose reversal agent such as naloxone or nalmefene [1][2]. The tablet label also describes hepatitis and clinically significant liver dysfunction in development and postmarketing, and hepatocellular injury in studies using up to 300 mg a day [1].

What is not known

Published LDN evidence is limited. The 2026 review concludes that current evidence does not support routine clinical use, and that safety data for LDN in pregnancy and in liver or kidney impairment are sparse [4].