What are the common side effects of Low-Dose Naltrexone (LDN) and how are they managed?

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Last updated: June 2, 2025View editorial policy

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From the Guidelines

Low-Dose Naltrexone (LDN) is generally well-tolerated, with common side effects including headache, tachycardia, and vivid dreams, which can be managed by starting with a low dose of 1.5 mg at bedtime and gradually increasing to a maximum dose of 4.5 mg. According to a study published in the journal Ophthalmology in 2017 1, LDN has been used effectively as an off-label treatment in patients with chronic neuropathic pain, including fibromyalgia, complex regional pain syndrome, low-back pain, and painful diabetic neuropathy. The study found that LDN 4.5 mg resulted in significant decrease of pain and improved satisfaction with life as compared to placebo.

Some key points to consider when managing side effects of LDN include:

  • Starting with a low dose of 1.5 mg at bedtime and gradually increasing to a maximum dose of 4.5 mg to minimize side effects
  • Taking LDN at bedtime to reduce sleep disturbances
  • Managing temporary headaches with acetaminophen
  • Taking LDN with food to reduce nausea
  • Monitoring for initial symptom flares in autoimmune conditions, which are often considered a positive sign that the medication is engaging with the immune system

It's worth noting that the side effects of LDN are typically mild and transient, and most patients are able to tolerate the medication well. As reported in the study 1, the common side effects of LDN include headache, tachycardia, and vivid dreams, which can be managed with proper dosing and monitoring. By following these guidelines, patients can minimize the risk of side effects and maximize the benefits of LDN treatment.

From the FDA Drug Label

While extensive clinical studies evaluating the use of naltrexone hydrochloride in detoxified, formerly opioid-dependent individuals failed to identify any single, serious untoward risk of naltrexone hydrochloride use, placebo-controlled studies employing up to five-fold higher doses of naltrexone hydrochloride (up to 300 mg per day) than that recommended for use in opiate receptor blockade have shown that naltrexone hydrochloride causes hepatocellular injury in a substantial proportion of patients exposed at higher doses Reported Adverse Events Naltrexone hydrochloride has not been shown to cause significant increases in complaints in placebo-controlled trials in patients known to be free of opioids for more than 7 to 10 days Studies in alcoholic populations and in volunteers in clinical pharmacology studies have suggested that a small fraction of patients may experience an opioid withdrawal-like symptom complex consisting of tearfulness, mild nausea, abdominal cramps, restlessness, bone or joint pain, myalgia, and nasal symptoms Alcoholism In an open label safety study with approximately 570 individuals with alcoholism receiving naltrexone hydrochloride, the following new-onset adverse reactions occurred in 2% or more of the patients: nausea (10%), headache (7%), dizziness (4%), nervousness (4%), fatigue (4%), insomnia (3%), vomiting (3%), anxiety (2%) and somnolence (2%) Opioid Addiction The following adverse reactions have been reported both at baseline and during the naltrexone hydrochloride clinical trials in opioid addiction at an incidence rate of more than 10%: Difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea and/or vomiting, low energy, joint and muscle pain, and headache

The common side effects of Low-Dose Naltrexone (LDN) include:

  • Gastrointestinal symptoms: nausea, vomiting, abdominal cramps
  • Neurological symptoms: headache, dizziness, nervousness, anxiety, insomnia
  • Musculoskeletal symptoms: joint and muscle pain, bone pain, myalgia
  • Psychiatric symptoms: depression, suicidal ideation, suicidal attempts These side effects are usually mild and transient, but can be managed by:
  • Dose adjustment: reducing the dose or switching to an alternative dosing pattern
  • Symptomatic treatment: using medications or other interventions to manage specific symptoms, such as anti-nausea medications or pain relievers
  • Monitoring: closely monitoring patients for signs of adverse reactions and adjusting treatment as needed 2, 2

From the Research

Common Side Effects of Low-Dose Naltrexone (LDN)

  • Insomnia: Studies have shown that naltrexone can affect sleep patterns, with some participants experiencing insomnia 3.
  • Anxiety and Depression: While some studies suggest that LDN may not have a significant impact on anxiety and depression 4, others indicate that it may be used to reduce symptoms related to chronic pain conditions, which can be comorbid with anxiety and depression 5.
  • Vivid Dreams: There is limited research on the specific side effects of LDN, but some users have reported experiencing vivid dreams.
  • Headaches: Some users have reported experiencing headaches when starting LDN, but this is not supported by the available research.

Management of Side Effects

  • Insomnia: Melatonin supplementation has been shown to improve sleep quality and duration, and may be a useful alternative for managing insomnia related to LDN use 6.
  • Anxiety and Depression: Participants with anxiety, depression, or insomnia should be closely monitored when starting LDN, and alternative treatments should be considered if symptoms worsen 4.
  • Dosage Adjustment: The dosage of LDN may need to be adjusted to minimize side effects, with some studies suggesting that low-dose naltrexone (0.01 mg/kg) may have different effects on motivation and behavior compared to higher doses 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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