LDN: A Sensible Treatment for Chronic Fatigue Syndrome and Fibromyalgia
What Is Low-Dose Naltrexone (LDN)?
First synthesized in 1963, naltrexone is an opioid antagonist meaning it blocks the body’s opioid receptors. It is commonly used in 50 mg doses to treat opioid overdose and addiction. In the late 1980s, researchers discovered that lower doses of naltrexone (1–5 mg), now known as low-dose naltrexone (LDN), could have therapeutic effects on immune disorders. Despite its potential, LDN is not FDA-approved for any condition yet, but that may soon change.
LDN for Fibromyalgia: What the Research Says
Promising Study Results
A 2009 pilot study of 10 women with fibromyalgia found that LDN at 4.5 mg significantly improved pain in 6 participants after 8 weeks. Follow-up studies in 2013 and 2018 further validated these findings, demonstrating reductions in both pain and inflammatory cytokines. For example:
2013 Study: A double-blind crossover trial showed 57% of participants experienced pain reduction and overall improvement.
2018 Study: Reported a 15% decrease in pain and an 18% reduction in overall symptoms.
The Role of ESR and Inflammatory Markers
Interestingly, individuals in the 2013 study with higher ESR (erythrocyte sedimentation rate), a marker of inflammation, responded better to LDN. While ESR levels remained in the normal range, those at the higher end saw the greatest benefits.
LDN for Other Conditions
LDN has also shown potential in other conditions, including:
Crohn’s Disease: Up to 80% of participants reported improvement in clinical studies.
Multiple Sclerosis: LDN may help reduce neuroinflammation.
Neuropathic Pain, HIV/AIDS, and Cancer: Ongoing studies suggest it could provide symptom relief.
For pediatric Crohn’s disease, biotech company TNI obtained FDA orphan drug status in 2013. If trials are successful, FDA approval may follow, potentially increasing its availability—albeit at higher costs.
How Does LDN Work?
LDN works by targeting toll-like receptor 4 (TLR-4), a key receptor on microglial cells in the brain. Microglia release inflammatory cytokines like IL-1, TNF-α, and interferon-β in response to stimuli, contributing to neuroinflammation and symptoms like fatigue, pain, and cognitive dysfunction.
Microglia and Neuroinflammation
Over-activated microglia are associated with:
Pain and fatigue.
Sleep and mood disorders.
Cognitive decline and neurodegeneration.
By inhibiting TLR-4, LDN reduces this overactivation, mitigating symptoms associated with conditions like ME/CFS, fibromyalgia, Alzheimer’s, and ALS.
Why LDN Is a Logical Treatment for ME/CFS and Fibromyalgia
Brain imaging studies in ME/CFS and fibromyalgia consistently show over-activated microglia and generalized neuroinflammation, which correlate with symptom severity. Traditional anti-inflammatories cannot cross the blood-brain barrier, but LDN can. Its dual mechanisms include:
Enhancing natural opioids (endorphins): Reduces pain and sickness behaviors.
Blocking TLR-4 receptors: Shuts down over-activated microglia and decreases inflammatory cytokines like IL-6, TNF-α, and IL-17.
These mechanisms make LDN a targeted treatment for reducing the root causes of symptoms in ME/CFS and fibromyalgia.
What Are the Side Effects of LDN?
LDN is widely regarded as safe and well-tolerated, with only mild side effects reported in studies:
Vivid dreams and headaches (often resolved by reducing the dose to 3 mg).
Insomnia (minimized by taking LDN earlier in the day).
LDN is considered safe to use alongside other medications, including opioids, though consultation with a healthcare provider is recommended.
How to Access LDN
LDN is relatively inexpensive and available in various forms, making it accessible to ME/CFS and fibromyalgia patients who require careful dose adjustments:
Capsules or tablets (1.5–4.5 mg)
Oral liquid formulations (1 mg/1 mL)
Sublingual drops
Topical preparations (limited evidence of effectiveness)
Where to Get LDN
United States: LDN can be purchased in capsule form without a prescription through Anti-Aging Systems. This is Dr. Craig’s preferred source. Be prudent before embarking on self-prescription. Always consult with a healthcare provider before starting LDN, and review the research to make informed decisions.
UK and EU: Telemedicine services like Clinic 158 offer online consultations for a prescription, with costs around £35 for the consultation and £20 for the prescription. Clinic 158.
Dr. Craig’s Experience With LDN
Dr. Craig shares personal anecdotes highlighting LDN’s ability to mitigate post-exertional malaise, a hallmark symptom of ME/CFS. Whether recovering from sleepless flights or physically demanding hikes, LDN provided quick relief, enabling activity levels that would otherwise have been impossible. Hear more about my LDN experience in a YouTube video on the topic.
Final Thoughts: Why LDN Is a Game-Changer
LDN offers a promising, affordable treatment for ME/CFS and fibromyalgia. By addressing neuroinflammation and reducing overactive microglia, LDN targets the underlying causes of symptoms in these conditions. Its low side effect profile and accessibility make it a practical option for patients seeking relief. Do you have experience using LDN? Please share in the comments.
References
Younger J, Parkitny L, McLain D. (2014) The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 33(4):451-9.
Toljan K, Vrooman B (2018) Low-Dose Naltrexone (LDN)-Review of Therapeutic Utilization. Med Sci (Basel). 6(4). pii: E82.
Lehnardt S (2010) Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Glia. 58(3):253-63.
Parkitny L, Younger J (2017) Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia. Biomedicines. 2017 Apr 18;5(2).
Cote B, Ross B, Fortner J, & Rao D. (2018) The Use and Utility of Low-dose Naltrexone Capsules for Patients with Fibromyalgia. Int J Pharm Compd. 22(3):252-256.
