Why Take Low-Dose Naltrexone at Night?

As an opioid receptor antagonist (also called an opiate antagonist), naltrexone is being used at higher doses (50 mg) for the treatment of alcohol and drug addiction. It does this by preventing the euphoric and sedating effects of addictive drugs. (1)

At lower doses (up to 4.5 mg), low-dose naltrexone (LDN) temporarily blocks opioid receptors in the body (the "feel good" chemicals endorphins and enkephalins). When this happens, your body produces more endogenous opioids, which are initially blocked. These endogenous opioids then flood the body in a "rebound" effect—endorphins and enkephalins. (1,2)

Off-label uses, non-addictive

Although naltrexone is FDA-approved at higher doses for addiction, LDN is used off-label for a variety of chronic conditions involving pain and inflammation. (3,4,5,6,7)

• Reduces inflammatory signaling, leading to decreased pain and inflammation
• May reduce brain fog, especially in patients with long COVID. Brain fog is often associated with inflammation, a result of impaired immune function.
• Autoimmune and inflammatory diseases, including multiple sclerosis, Crohn's disease, inflammatory bowel disease, autoimmune thyroid disease, and arthritis
• Chronic pain syndromes such as fibromyalgia and neuropathic pain
• Erythrodermic psoriasis
• Autoimmune alopecia (hair loss)
• Under investigation as a solo and adjunct treatment for various cancers (lung, breast, ovarian, etc.) (8)

How to take LDN

Start low, stay consistent

Your provider will start you at a very low dose and increase it as tolerated. LDN can take several months to provide meaningful relief from symptoms.

Take it at night.

Your body is in repair mode when you sleep. During this time, inflammation and cytokine production increase, while anti-inflammatory cortisol levels decrease. With a half-life of 4–6 hours, taking LDN before bedtime can help decrease inflammation and regulate immune response. (1,6,10)

Medications to avoid

Low-dose naltrexone (LDN) is generally safe to combine with most antidepressants.

• It may enhance their effectiveness, particularly for treatment-resistant depression or co-occurring chronic pain. However, bupropion (Wellbutrin) may cause high blood pressure and a faster heart rate. (9)
• Avoid all forms of opioids (including tramadol, oxycodone, and codeine), as they can cause severe withdrawal and render pain medication ineffective. Avoid alcohol, which can cause excessive drowsiness.
• Consult a doctor regarding immunosuppressants. (2)

Side effects

While generally well tolerated, LDN does carry some side effects:

• Difficulty sleeping (insomnia)
• Nausea
• Nightmares or vivid dreams
• Rarely, prolonged erections (priapism)
• Rarely, weight loss

LDN is best thought of as a long-term, foundational therapy. It may take a few months to notice improvement, and for some, up to a year.

With consistent use, many people report:

• Gradual reduction in pain
• Fewer inflammatory "flares" and quicker recovery
• Better sleep quality and clearer thinking
• A general sense of improved resilience and well-being

Safe, effective, and with few side effects. Low-dose naltrexone holds promise for alleviating many symptoms of modern life—namely, inflammation.

References

1. Toljan K, Vrooman B. Low-dose naltrexone (LDN)—review of therapeutic utilization. Med Sci (Basel). 2018;6(4):82. doi:10.3390/medsci6040082.
2. Center for Pain Management. Low dose naltrexone. Center for Pain Management. https://www.centerforpain.net/low-dose-naltrexone. Accessed February 5, 2026.
3. de Carvalho, J. F., & Skare, T. (2023). Low-Dose Naltrexone in Rheumatological Diseases. Mediterranean journal of rheumatology, 34(1), 1–6. https://doi.org/10.31138/mjr.34.1.1
4. Long-COVID symptoms- preliminary studies reveal relief from long covid symptoms, such as Bonilla, H., Tian, L., Marconi, V. C., Shafer, R., McComsey, G. A., Miglis, M., Yang, P., Bonilla, A., Eggert, L., & Geng, L. N. (2023). Low-dose naltrexone use for the management of post-acute sequelae of COVID-19. International immunopharmacology, 124(Pt B), 110966. https://doi.org/10.1016/j.intimp.2023.110966
5. Isman A, Nyquist A, Strecker B, Harinath G, Lee V, Zhang X, Zalzala S. Low-dose naltrexone and NAD+ for the treatment of patients with persistent fatigue symptoms after COVID-19. Brain Behav Immun Health. 2024 Feb 1;36:100733. doi: 10.1016/j.bbih.2024.100733. PMID: 38352659; PMCID: PMC10862402.
6. Beltran Monasterio E. P. (2019). Low-dose Naltrexone: An Alternative Treatment for Erythrodermic Psoriasis. Cureus, 11(1), e3943. https://doi.org/10.7759/cureus.3943
7. American Hair Loss Association. (n.d.). Low dose naltrexone: A new frontier in the battle against hair loss. https://www.americanhairloss.org/low-dose-naltrexone-a-new-frontier-in-the-battle-against-hair-loss
8. Khan, A. (2018). Low dose naltrexone in cancer prevention and treatment [Conference presentation]. LDN Research Trust Conference. https://ldnresearchtrust.org/sites/default/files/inline-files/Dr-Akbar-Khan.pdf
9. MedlinePlus. (n.d.). Naltrexone and bupropion. U.S. National Library of Medicine. https://medlineplus.gov/druginfo/meds/a6190
10. Krueger J. M. (2008). The role of cytokines in sleep regulation. Current pharmaceutical design, 14(32), 3408–3416. https://doi.org/10.2174/138161208786549281
    

Written by Brooke Lounsbury