Low-Dose Naltrexone (LDN) Side Effects

Reported Low-Dose Naltrexone (LDN) side effects

In low-dose trials In the two largest placebo-controlled fibromyalgia trials, adverse events were about as common with low-dose naltrexone as with placebo. In the Danish FINAL trial, 84 percent on low-dose naltrexone and 86 percent on placebo had an adverse event, 8 percent against 6 percent stopped because of one, and the only serious adverse event occurred on placebo (PMID: 38258677). In the Spanish INNOVA trial, 68.8 percent on low-dose naltrexone and 72 percent on placebo had an adverse event, mostly mild and short-lived, and none of five serious adverse events (four on low-dose naltrexone, one on placebo) was judged treatment related (PMID: 42385209). In INNOVA, nervous system disorders made up 21.1 percent of adverse events on low-dose naltrexone and 8.5 percent on placebo (p=0.024) (PMID: 42385209). A 2025 meta-analysis that included seven randomized chronic pain trials found more adverse events with low-dose naltrexone than with placebo (incidence rate ratio 1.4, 95% CI 1.12 to 1.75) (PMID: 40540205). Sleep and dreams. Sleep disturbance was the most common side effect in the 2007 Crohn's disease pilot, reported by 7 of 17 patients (PMID: 17222320). In the 2009 Stanford fibromyalgia pilot, insomnia and vivid dreams were rare, minor and transient (PMID: 19453963). In the 2011 Crohn's disease trial, insomnia was reported by 5 patients in each group and unusual dreams by 2 on naltrexone and 3 on placebo (PMID: 21380937). A 2025 meta-analysis of fibromyalgia trials found vivid dreams more often with low-dose naltrexone than with placebo (risk ratio 2.41, 95% CI 1.77 to 3.28) (PMID: 40337423). In the 2026 Auckland depression trial, nightmares or abnormal dreams that participants attributed to treatment were reported by 8 of 19 on low-dose naltrexone and 3 of 18 on placebo, and sleep problems by 7 and 5 (PMID: 41868116). Headache, nausea, fatigue and diarrhea. In a 2023 Danish crossover trial, patient diaries recorded headache in 9 people during low-dose naltrexone and 9 during placebo, fatigue in 9 and 4, nausea in 8 and 5, and dizziness in 7 and 4, all classed as minor; two people dropped out with nausea and vomiting just after starting (PMID: 38226027). The 2025 fibromyalgia meta-analysis found no significant link between low-dose naltrexone and headache (PMID: 40337423). Mild diarrhea was the most common adverse event with naltrexone in a diabetic neuropathy trial (PMID: 34014028), and 2 of 38 people who started low-dose naltrexone in an Irish long COVID study stopped because of new diarrhea (PMID: 35814187). A 2018 Cochrane review of the Crohn's disease trials found no significant differences from placebo in withdrawals for adverse events or in sleep disturbance, unusual dreams, headache, decreased appetite, nausea or fatigue, and no serious adverse events (PMID: 29607497). Serious adverse events across doses. A 2019 meta-analysis of 89 placebo-controlled trials of oral naltrexone at any dose (11,194 participants, with studies in opioid users excluded) found no increase in serious adverse events, risk ratio 0.84 (95% CI 0.66 to 1.06) (PMID: 30642329). The result was consistent across doses and conditions, and 26 of the trials, with 4,960 participants, reported serious adverse events by group (PMID: 30642329). At standard doses In an open-label safety study of about 570 people with alcoholism taking naltrexone tablets, new adverse reactions in 2 percent or more were nausea (10 percent), headache (7 percent), dizziness (4 percent), nervousness (4 percent), fatigue (4 percent), insomnia (3 percent), vomiting (3 percent), anxiety (2 percent) and somnolence (2 percent) (US prescribing information for naltrexone tablets). The label also reports depression, suicide, suicide attempts and suicidal thinking after marketing in people treated for opioid dependence, with no causal relationship shown (US prescribing information for naltrexone tablets). Liver The naltrexone tablet label warns that hepatitis and clinically significant liver dysfunction were seen during clinical development and after marketing, often alongside other possible causes such as alcoholic liver disease, hepatitis B or C, or other liver-toxic drugs (US prescribing information for naltrexone tablets). The label describes the liver injury as dose related: at 300 mg a day, 5 of 26 obese people (19 percent) and none of 24 on placebo developed raised transaminases after three to eight weeks (US prescribing information for naltrexone tablets). Naltrexone exposure (AUC) was about 5 and 10 times higher in compensated and decompensated cirrhosis (US prescribing information for naltrexone tablets). The boxed warning for hepatotoxicity has been removed from oral and injectable naltrexone labeling (PMID: 26717532), and a hospital medicine review on alcohol use disorder stated that earlier hepatotoxicity concerns had been disproven and that recent studies showed naltrexone to be safe in people with cirrhosis (PMID: 39655573). Liver data at low doses are limited. The 2007 Crohn's disease pilot noted no laboratory abnormalities (PMID: 17222320). The 2011 Crohn's disease trial excluded people with abnormal liver enzymes and recorded transient transaminase rises in 2 patients on naltrexone that resolved within a month, one of them during a respiratory infection (PMID: 21380937). A Penn State chart review of 54 people with multiple sclerosis found no significant differences in standard blood test values over follow-up of up to 50 months after diagnosis (PMID: 28607740). Opioids Naltrexone can bring on opioid withdrawal in anyone who is not free of opioids; the label describes symptoms within five minutes of a dose, lasting up to 48 hours, and postmarketing cases severe enough for hospital or intensive care admission (US prescribing information for naltrexone tablets). The label also warns that people may be more sensitive to opioids, even at lower doses, after naltrexone is stopped, that fatal overdoses have been reported after treatment ended, and that trying to overcome the blockade with large opioid doses can cause life-threatening or fatal overdose; the label does not address low doses (US prescribing information for naltrexone tablets). A 2017 case report described the opposite problem: a man taking low-dose naltrexone for multiple sclerosis became unresponsive after a single 5 mg dose of oxycodone and needed naloxone and a night in intensive care, and the authors suggested that low-dose naltrexone may make people more sensitive to opioids (PMID: 28410920). Pregnancy, breastfeeding and children The naltrexone label states that there are no adequate and well-controlled studies in pregnant women, that naltrexone increased early fetal loss in rats and rabbits at doses well above human doses, that it is unknown whether naltrexone passes into human milk, and that safe use under 18 years of age has not been established (US prescribing information for naltrexone tablets). A pilot trial of low-dose naltrexone in 14 children with Crohn's disease reported no serious adverse events (PMID: 23188075).

When to continue, reduce, or stop Low-Dose Naltrexone (LDN)

Low-Dose Naltrexone (LDN) contraindications

Opioid use. The naltrexone label lists as contraindications people receiving opioid pain medicines, people currently dependent on opioids, including those maintained on methadone or buprenorphine, people in acute opioid withdrawal, anyone who has failed a naloxone challenge test or has a positive urine screen for opioids, and anyone with a history of sensitivity to naltrexone (US prescribing information for naltrexone tablets). Precipitated withdrawal. For people previously dependent on short-acting opioids, the label calls for an opioid-free interval of at least 7 to 10 days before naltrexone is started, and it says people coming off buprenorphine or methadone may be vulnerable to precipitated withdrawal for as long as two weeks (US prescribing information for naltrexone tablets). Opioid overdose after stopping. The label warns that people may be more sensitive to opioids, even at lower doses, after naltrexone is stopped, that fatal overdoses have been reported after treatment ended, and that attempts to overcome the blockade with large opioid doses are especially dangerous; the label does not address low doses (US prescribing information for naltrexone tablets). Emergency pain care. The label states that in an emergency needing opioid pain relief, people on fully blocking doses may need more opioid than usual, with deeper and longer depression of breathing, and that reactions such as facial swelling, itching and bronchoconstriction may occur; the label does not address low doses (US prescribing information for naltrexone tablets). A case report described unresponsiveness after a small oxycodone dose in a person on low-dose naltrexone (PMID: 28410920). Liver disease. The label warns of hepatitis and clinically significant liver dysfunction, reports about 5- and 10-fold higher naltrexone exposure in compensated and decompensated cirrhosis, and notes that adequate studies in severe liver or kidney impairment have not been done (US prescribing information for naltrexone tablets). Kidney impairment. Naltrexone and its main metabolite leave the body mainly in urine, and the label advises caution in kidney impairment (US prescribing information for naltrexone tablets). Depression. The label reports depression and suicidal thinking after marketing in people treated for opioid dependence, with no causal relationship shown, and calls for monitoring (US prescribing information for naltrexone tablets). Pregnancy, breastfeeding and children. The label reports no adequate human studies in pregnancy, unknown passage into human milk, and no established safe use under 18 years of age (US prescribing information for naltrexone tablets).

Why vendor quality drives Low-Dose Naltrexone (LDN) side-effect frequency

Research-compound communities consistently report that adverse-event frequency tracks with source quality. Three reasons: (1) impurity profiles vary by lab (residual synthesis byproducts can trigger reactions); (2) mislabeled mass means actual dose can be 50-150% of stated dose; (3) reconstitution-grade water and capping methodology affect long-term storage stability. COA-verified vendors with published HPLC data minimize all three failure modes. Check a vendor's COA record and Trust Score before you buy.

Low-Dose Naltrexone (LDN) side effects FAQ

Research-use disclaimer. All safety information on this page summarizes published research literature and community-reported reactions. It is not medical advice and not authorization for human consumption. Always consult a licensed practitioner before any compound enters a clinical context. Compounds linked from this page are sold for research-use only.
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