Low Dose Naltrexone for chronic pain and fatigue in Ehlers Danlos Syndrome

Exploring the Benefits of Low Dose Naltrexone in Ehlers-Danlos Syndrome

Ehlers-Danlos Syndrome (EDS) is a group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. For many patients, chronic pain becomes a significant and often debilitating feature of their condition, posing a major challenge for long-term management. While conventional treatments such as physical therapy, analgesics, and muscle relaxants are often used, their effectiveness can be limited and side effects significant. This has prompted interest in alternative or adjunctive therapies—one of which is Low Dose Naltrexone (LDN).

What is Low Dose Naltrexone?

Naltrexone is traditionally used in much higher doses (50 mg or more) to manage alcohol and opioid dependence. However, when used at doses ranging from 0.5 mg to 4.5 mg, it has been found to exhibit unique immunomodulatory and anti-inflammatory properties without the opioid-blocking effects seen at higher doses.

Why Consider LDN for EDS?

1. Chronic Pain Relief
   Many EDS patients experience pain that is disproportionate to imaging findings or injury, often neuropathic or central in nature. LDN has been shown to reduce central sensitization—one of the key contributors to chronic pain in EDS. By modulating glial cell activity and reducing neuroinflammation, LDN can help “reset” the pain threshold, potentially offering relief in a way that typical analgesics do not.

2. Improved Sleep and Fatigue
   EDS is frequently associated with poor sleep quality, fatigue, and cognitive dysfunction (often referred to as "brain fog"). Some patients on LDN report more restorative sleep and improved mental clarity—benefits that may be tied to better regulation of the endorphin system and decreased cytokine levels.

3. Immunomodulation
   Several subtypes of EDS have an autoimmune or mast cell activation component. LDN’s ability to reduce pro-inflammatory cytokines like TNF-α and interleukin-6 may help in controlling systemic inflammation, especially in patients with comorbid conditions like fibromyalgia, POTS, or autoimmune symptoms.

4. Low Side Effect Profile
   At low doses, naltrexone is generally well-tolerated. Side effects are rare and typically mild—such as vivid dreams or transient headaches. This makes it a favorable option compared to opioids or other immunomodulators, particularly in long-term management.

Clinical Evidence and Patient Experience

Though large-scale randomized controlled trials are limited, emerging evidence and case reports support LDN’s role in chronic pain conditions such as fibromyalgia, complex regional pain syndrome (CRPS), and Crohn’s disease—many of which share pathophysiological similarities with EDS. Anecdotal reports and small open-label studies suggest that some EDS patients respond well to LDN, especially those with prominent neuropathic or inflammatory symptoms.

Practical Considerations

• Starting Dose: Begin at 0.5 mg and titrate slowly to a target of 3.0–4.5 mg nightly.
• Compounding Required: Since LDN is not commercially available in low doses, it must be specially compounded by a pharmacy experienced in LDN preparations.
• Avoid Opioids: As even low doses of naltrexone can block opioid receptors, it is contraindicated in patients actively using opioids.

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1. Chopra P, Cooper M: Treatment of Complex Regional Pain Syndrome (CRPS) using Low Dose Naltrexone (LDN). J Neuroimmune Pharmacol DOI 10.1007/s 11481-013-9451-y, March 2013

This is an orginal publication that discussed the use of LDN in chronic for the first time

2. Patten DK, Schultz BG, Berlau DJ.
The safety and efficacy of low-dose naltrexone in the management of chronic pain and inflammation.
Journal of Pain Research. 2018;11:2589–2597.
https://doi.org/10.2147/JPR.S181706
→ A review paper summarizing current evidence on LDN in chronic pain and inflammation.

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