Can low-dose naltrexone (LDN) be used as an adjunct therapy for autoimmune patients?

Low-Dose Naltrexone as Adjunct Therapy for Autoimmune Patients

Low-dose naltrexone (LDN) is not recommended as an adjunct therapy for autoimmune patients based on current clinical guidelines, which suggest against its use for inducing or maintaining remission in autoimmune conditions. 1

Evidence Assessment

Primary Guideline Recommendations

The Canadian Association of Gastroenterology's clinical practice guideline for Crohn's disease (2019) explicitly recommends against the use of naltrexone:

• "In patients with CD, we suggest against the use of naltrexone to induce OR maintain symptomatic remission." (Conditional recommendation, low-quality evidence for induction, very low-quality evidence for maintenance) 1
• This recommendation was strongly supported by the guideline panel (65% strongly agree, 35% agree)

Mechanism and Pharmacology

Naltrexone is an opioid antagonist that:

• Primarily blocks mu, kappa, and delta opioid receptors
• At standard doses (50mg), is FDA-approved for alcohol and opioid dependence 1
• Has a plasma half-life of 4 hours, with an active metabolite (6-b-naltrexol) having a half-life of 13 hours 1
• At low doses (typically 1-4.5mg), has been theorized to have immunomodulatory effects through different mechanisms than its standard opioid antagonism

Limited Evidence for Autoimmune Conditions

While some small studies suggest potential benefits in specific autoimmune conditions, the evidence is insufficient to support clinical use:

• A case report described successful use of LDN for guttate psoriasis in a 75-year-old male patient 2
• A Norwegian prescription database study suggested that persistent LDN users with rheumatoid and seropositive arthritis had reduced dispensing of disease-modifying antirheumatic drugs (DMARDs) by 6.7 percentage points and reduced use of NSAIDs and opioids 3
• A 2023 review noted LDN may help with symptoms in fibromyalgia, Sjögren's syndrome, scleroderma, and dermatomyositis, but emphasized that "data is limited and needs to be reproduced in larger studies" 4

Recent Clinical Trial Evidence

A 2023 randomized, double-blind, placebo-controlled crossover trial specifically examining LDN for arthritis pain found:

• No difference in pain interference between LDN and placebo
• No significant differences in pain severity, fatigue, depression, or health-related quality of life
• The authors concluded that findings "do not support LDN being efficacious in reducing nociceptive pain due to arthritis" 5

Important Clinical Considerations

If a patient is already taking LDN and requires surgery:

• Oral naltrexone should be held for 2-3 days prior to elective surgical procedures if opioids are expected to be used perioperatively 1
• For extended-release naltrexone, it should be held for 24-30 days after the last injection before elective procedures 1

Potential Risks and Contraindications

LDN should not be used in patients:

• Requiring short-term or long-term opioid therapy, as it could reduce analgesic efficacy or precipitate withdrawal 1
• Undergoing procedures requiring opioids (should be discontinued beforehand) 1
• With seizure disorders (particularly when combined with bupropion) 1

Conclusion

Based on current guidelines and evidence, LDN cannot be recommended as an adjunct therapy for autoimmune conditions. The highest quality evidence (clinical practice guidelines) explicitly recommends against its use in Crohn's disease, and recent clinical trials have failed to demonstrate efficacy for arthritis pain. Patients seeking adjunctive therapies for autoimmune conditions should be directed toward evidence-based treatments with established efficacy and safety profiles.