Low-dose naltrexone (LDN) for autoimmune disease means taking very small doses of naltrexone, usually at bedtime, to calm inflammation and pain signaling. This small dose at bedtime blocks opiate receptors in the brain, producing a rebound in endogenous opiates for the next 24 hours. This increase in endogenous opiates is the basis for clinical benefit. (22-23)
LDN is used off-label, and the evidence is early, with small trials and mixed results. Some people notice changes within weeks, others need longer, and some see no benefit. Knowing the timeline, side effects, and safety limits helps you judge it fairly.
What Is LDN and Why Is It Used?
In 2013, Dr. Jeffrey Dach described the history of the low-dose naltrexone protocol and its first clinical uses in his series beginning with Low Dose Naltrexone Part One. Naltrexone is an opioid receptor blocker. At low doses, usually 3 to 4.5 mg, it is thought to reduce inflammation and pain through opioid receptors and an immune receptor called TLR4. Within the brain, the immune cells are called microglia. These microglia are another proposed target. In 2017, Dr. Rachel Cant found LDN reduces inflammatory cytokines such as IL-6 and TNF-alpha which cause microglial activation (inflammation in the brain). The mechanisms are still being worked out. (13)
Standard naltrexone is a 50 mg tablet FDA approved for treatment of alcohol addiction.
This 50 mg dose is much higher than the 3-4.5 mg dose used for low dose LDN. This is made by a compounding pharmacy and prescribed off-label. The FDA regulators have not approved LDN for autoimmune conditions. So, it is being used off-label. For an overview and background on this topic, see: what low-dose naltrexone is and who may benefit. Dr. Dach’s earlier writing traces the history of the low-dose naltrexone protocol back to its first clinical use. This article focuses on what the experience looks like. (10-12)
Interest in LDN for autoimmune disease largely comes from patient reports and small studies, so one must have realistic expectations. (1-3)
How Strong Is the Evidence?
The evidence is limited. Most human studies are small trials or retrospective analyses, and larger controlled studies are still needed.
Inflammatory Bowel Disease
In 2018, Dr. Mitchell Lie reviewed the use of low dose Naltrexone for remission in inflammatory bowel disease, finding clinical improvement in about 75% of patients, writing:
Low dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers. Inflamed mucosa from IBD patients showed high ER stress levels, which was reduced in patients treated with LDN. Cytokine levels in neither epithelial cells nor serum from IBD patients were affected. Naltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal ER stress levels. Low dose Naltrexone treatment is effective and safe, and could be considered for the treatment of therapy refractory IBD patients. (16-17)
In 2018, Dr. Claire E. Parker and colleagues published a Cochrane review of Crohn’s disease that found two small trials with 46 participants and rated the certainty as low. In the adult trial, 12 weeks of 4.5 mg daily beat placebo on clinical response, 83 percent versus 38 percent, and on endoscopic response, 72 percent versus 25 percent. Although response rate was impressive, the complete remission rate was not statistically significant, and no serious adverse events were reported.
For more on this topic, see this article on a case report on Crohn’s disease using LDN: Remission from Crohn’s Disease with Low Dose Naltrexone. Case reports can illustrate what a response looks like, but it cannot replace randomized controlled trials. Unfortunately, since LDN is off-patent, there is no financial incentive to do expensive trials.(4-6)
Multiple Sclerosis
In 2008, Dr. M. Gironi and colleagues conducted a six-month pilot of 40 people with primary progressive multiple sclerosis (MS) and found LDN generally safe and well tolerated. (7-9)
In 2016, Dr. Michael Ludwig did a retrospective chart review of 54 patients with relapsing-remitting MS treated with LDN (alone or as adjunct) over years found no disease exacerbation, stable MRI scans and walking times, and overall clinical stability without toxicity. (20)
In 2014, Dr. Turel did a respective review of 215 MS patients exposed to LDN; substantial proportions reported good or excellent effect on fatigue and improved or stable perception of MS and quality of life; generally well tolerated. (21)
Fibromyalgia, Chronic Pain, Cancer, and Sarcoidosis
The strongest signals for LDN benefit appear in fibromyalgia and chronic pain, as discussed in the article: Low Dose Naltrexone Part Four. For Hashimoto’s thyroiditis, reports are mostly anecdotal, with no published trials showing efficacy. That gap is why we call LDN for autoimmune disease a trial, never a promise.
In 2006, Dr. Burt Berkson published a case report of a good outcome using LDN to treat B-cell Lymphoma. Another case report by Dr. Berkson in 2007 used LDN combined with Alpha Lipoic Acid to obtain long-term survival in a patient with pancreatic cancer. (14-15)
In 2017, Dr. Leonard Weinstock found LDN useful for two patients with sarcoidosis, writing;
In this report, a patient with systemic sarcoidosis was treated with LDN which increases endorphin levels and helps regulate inflammation including lymphocyte activity. This mechanism of action could play a role in the treatment of sarcoidosis. The radiographic improvement helped substantiate the therapeutic efficacy in the case study. Clinical improvement was seen in her fatigue and ability to stop taking antibiotic therapy for the sarcoid rash. It is unclear if the perceived improvement in dyspnea was directly responsible from LDN. The pulmonary function test did not improve but this is not surprising since cardiopulmonary exercise testing may be the most discriminant test in sarcoidosis. After seeing success in this case, we administered LDN to a 64 year old African American female with pulmonary sarcoidosis. She had required steroids and oxygen on and off over the past few years. Two months after initiating therapy with LDN she reported less dyspnea and was able to reduce the need for oxygen. As was seen in the case report, the most dramatic improvement was noted in her fatigue…Further studies are required to substantiate the efficacy of LDN in a variety of sarcoidosis involvement. (18)
What Should You Expect When You Start?
Expect a low starting dose, often a 3 mg bedtime capsule, with slow increases over time. The goal is to limit side effects while watching for benefit. LDN is also made as a liquid, sublingual drops, or a cream. If side effects appear, the prescriber may lower the dose for a while before increasing it again.
Common effects include:
- Sleep disturbance and vivid dreams, which often appear early
- Headache and nausea
- Mood changes
Many people have no significant side effects. Slower increases usually ease vivid dreams. In MS, fewer than 10 percent of people report a temporary symptom flare for several weeks.
Timing varies. Some people notice improvement within several weeks, others need longer observation, and benefits can occasionally take two to three months. Keep a simple symptom diary so you can compare honestly.
Who Should Avoid LDN?
Anyone using opioids should avoid it. LDN can block opioid pain medicine and trigger withdrawal, including with some opioid-containing cough products.
Tell your clinician about:
- Current or past opioid or naltrexone use
- Liver or kidney disease
- Planned surgery
- Every medication, herb, and supplement you take
Studies suggest LDN is compatible with some disease-modifying therapies, but confirm that with your specialist. Source matters as well. Medicine from unregulated online sellers cannot be guaranteed to contain LDN or to be safe, so use a licensed prescriber and pharmacy. Report any new symptom promptly, and never start or stop other medicines on your own.
How Do You Know Whether It Is Working?
Judge LDN for autoimmune disease by symptoms and labs together, not by one good week. Track pain, fatigue, sleep, and flares, and repeat relevant tests. A realistic plan sets review points, for example, after several weeks and again after a few months, so a trial doesn’t drift on indefinitely.
For autoimmune thyroid disease, antibody results and thyroid levels need careful interpretation. For autoimmune thyroid disease, see the article on: TPO and TgAb thyroid antibodies which explains what antibody results mean. And see the article on how often we check thyroid levels, including retesting.
Stress can drive flares, as described in this article: how stress can trigger Hashimoto’s flare-ups.
Fatigue, brain fog, and pain that overlap with hormone or thyroid imbalance suggest the need to check thyroid and hormone levels first. Disrupted sleep can also stem from chronic stress and elevated cortisol. Decisions are based on history, symptoms, and the full lab panel, as outlined on our services page.
What Should You Do Next?
LDN for autoimmune disease can be a reasonable trial for some people, but it is not a cure, and the evidence is still developing. Start with a full medical evaluation with history and physical examination, laboratory studies, and careful follow up. If you are considering LDN, contact our Davie, FL office to discuss whether it fits your situation. Bring your symptom diary and a full medication list. (19)
Frequently Asked Questions
1. Is LDN for autoimmune disease FDA-approved?
No. Naltrexone was approved at 50 mg for addiction. LDN for autoimmune conditions is compounded and used off-label.
2. How long does LDN take to work?
Some people notice improvement within several weeks. Others need longer, and benefits can occasionally take two to three months.
3. What are the common side effects?
Sleep disturbance, vivid dreams, headache, nausea, and mood changes. Vivid dreams often appear early and may ease with slower dose increases.
4. Can I take LDN with opioid pain medicine?
No. LDN can block opioids and trigger withdrawal. Tell your clinician about every opioid-containing product you use.
5. Does LDN cure autoimmune disease?
No. Research suggests some people may see symptom improvement, but no evidence shows it cures autoimmune disease.
6. Is it safe to buy LDN online?
Unregulated sellers cannot guarantee the product contains LDN or is safe. Use a licensed prescriber and pharmacy.
Articles With Related Interest:
Low Dose Naltrexone Part Three, Remission from Crohn’s Disease
The Non-Mystery of Chronic Fatigue
References
1. Smith, Jill P., et al. “Therapy with the Opioid Antagonist Naltrexone Promotes Mucosal Healing in Active Crohn’s Disease: A Randomized Placebo-Controlled Trial.” *Digestive Diseases and Sciences*, vol. 56, no. 7, 2011, pp. 2088–97.
2. Gironi, M., et al. “A Pilot Trial of Low-Dose Naltrexone in Primary Progressive Multiple Sclerosis.” *Multiple Sclerosis Journal*, vol. 14, no. 8, 2008, pp. 1076–83.
3. Parker, Claire E., et al. “Low Dose Naltrexone for Induction of Remission in Crohn’s Disease.” *Cochrane Database of Systematic Reviews*, 2018, issue 4, CD010410.
4. Parker, Claire E., et al. “Low Dose Naltrexone for Induction of Remission in Crohn’s Disease.” *Cochrane Database of Systematic Reviews*, 2018, issue 4, CD010410.
5. Smith, Jill P., et al. “Therapy with the Opioid Antagonist Naltrexone Promotes Mucosal Healing in Active Crohn’s Disease: A Randomized Placebo-Controlled Trial.” *Digestive Diseases and Sciences*, vol. 56, no. 7, 2011, pp. 2088–97.
6. Smith, Jill P., et al. “Low-Dose Naltrexone Therapy Improves Active Crohn’s Disease.” *American Journal of Gastroenterology*, vol. 102, no. 4, 2007, pp. 820–28.
7. Gironi, M., et al. “A Pilot Trial of Low-Dose Naltrexone in Primary Progressive Multiple Sclerosis.” *Multiple Sclerosis Journal*, vol. 14, no. 8, 2008, pp. 1076–83.
8. Cree, Bruce A. C., et al. “Pilot Trial of Low-Dose Naltrexone and Quality of Life in Multiple Sclerosis.” *Annals of Neurology*, vol. 68, no. 2, 2010, pp. 145–50..
9. Ludwig, M. D., et al. “Long-Term Treatment with Low Dose Naltrexone Maintains Stable Health in Patients with Multiple Sclerosis.” *Multiple Sclerosis Journal – Experimental, Translational and Clinical*, 2016.
10. U.S. Food and Drug Administration / DailyMed. “Naltrexone Hydrochloride Tablets USP 50 mg.” DailyMed,
11. StatPearls. “Naltrexone.” NCBI Bookshelf,
12. Substance Abuse and Mental Health Services Administration (SAMHSA). “Chapter 4—Oral Naltrexone.” Incorporating Alcohol Pharmacotherapies Into Medical Practice, NCBI Bookshelf
13. Cant, Rachel, Angus G. Dalgleish, and Rachel L. Allen. “Naltrexone inhibits IL-6 and TNFα production in human immune cell subsets following stimulation with ligands for intracellular toll-like receptors.” Frontiers in Immunology 8 (2017): 809.
14. Berkson, Burton M., Daniel M. Rubin, and Arthur J. Berkson. “Reversal of signs and symptoms of a B-cell lymphoma in a patient using only low-dose naltrexone.” Integrative cancer therapies 6.3 (2007): 293-296. Reversal B Cell Lymphoma Using Low Dose Naltrexone Integr Cancer Ther Burton Berkson 2007
15. Berkson, Burton M., Daniel M. Rubin, and Arthur J. Berkson. “The long-term survival of a patient with pancreatic cancer with metastases to the liver after treatment with the intravenous α-lipoic acid/low-dose naltrexone protocol.” Integrative cancer therapies 5.1 (2006): 83-89.
16. Lie, Mitchell RKL, et al. “Low dose Naltrexone for induction of remission in inflammatory bowel disease patients.” Journal of Translational Medicine 16 (2018).
17. Weinstock, Leonard B. “Naltrexone Therapy for Crohn’s Disease and Ulcerative Colitis.” Journal of clinical gastroenterology 48.8 (2014): 742. Naltrexone Therapy Crohns Disease Ulcerative Colitis Weinstock Leonard B J clin gastroenterology 2014
18. Weinstock, Leonard, Trisha L. Myers, and Anup Shetty. “Low-dose Naltrexone for the treatment of sarcoidosis.” Sarcoidosis vasculitis and diffuse lung disease 34.2 (2017): 184-187. Low-dose Naltrexone for Sarcoidosis Weinstock Leonard Sarcoidosis vasculitis lung disease 2017
19. Toljan, Karlo, and Bruce Vrooman. “Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization.” Medical Sciences 6.4 (2018): 82. Low Dose Naltrexone LDN Review of Therapeutic Utilization Toljan Karlo Bruce Vrooman Medical Sciences 2018
20. Ludwig, Michael D., et al. “Long-Term Treatment with Low Dose Naltrexone Maintains Stable Health in Patients with Multiple Sclerosis.” Multiple Sclerosis Journal – Experimental, Translational and Clinical, vol. 2, 2016, 2055217316672242. https://doi.org/10.1177/2055217316672242.
21. Turel, A. P., et al. (Penn State Hershey MS Clinic retrospective series, presented/abstracted 2014). “Safety, Tolerability, and Benefits of Low-Dose Naltrexone in Patients with Multiple Sclerosis: A Retrospective Review.” CMSC 2014 abstract / clinic data. https://cmsc.confex.com/cmsc/2014/webprogram/Handout/Paper2771/CMSCLDN2014.pdf.
22. Donahue, Renee N., Patricia J. McLaughlin, and Ian S. Zagon. “Low-Dose Naltrexone Targets the Opioid Growth Factor–Opioid Growth Factor Receptor Pathway to Inhibit Cell Proliferation: Mechanistic Evidence from a Tissue Culture Model.” *Experimental Biology and Medicine*, vol. 236, no. 9, 2011, pp. 1036–50.
23. Zagon, Ian S., and Patricia J. McLaughlin. “Intermittent Blockade of OGFr and Treatment of Autoimmune Disorders.” *Experimental Biology and Medicine*, vol. 243, no. 15-16, 2018, pp. 1323–30.
24. Younger, Jarred, Luke Parkitny, and David McLain. “The Use of Low-Dose Naltrexone (LDN) as a Novel Anti-Inflammatory Treatment for Chronic Pain.” *Clinical Rheumatology*, vol. 33, no. 4, 2014, pp. 451–59.
