Exploring Low-Dose Naltrexone (LDN) as a Potential Therapy for Chiari Malformation: San Antonio and Quincy

August 20, 2025

Chiari malformation (CM) is a structural neurological condition where the cerebellar tonsils herniate through the foramen magnum, often disrupting cerebrospinal fluid (CSF) flow and causing symptoms like chronic headaches, neck pain, balance issues, and paresthesias. In some cases, it’s linked with comorbidities such as syringomyelia or Ehlers-Danlos Syndrome (EDS) [1,2]. Managing CM symptoms, particularly pain, remains a clinical challenge due to limited evidence-based treatments. Enter Low-Dose Naltrexone (LDN), an off-label use of the opioid antagonist naltrexone at doses of 0.1 mg –4.5 mg, which has sparked interest for its anti-inflammatory and immunomodulatory effects. By suppressing central nervous system (CNS) glial activation and boosting endorphin production, LDN may address central sensitization in chronic pain states [2,3]. Could LDN offer relief for CM patients? This blog post dives into the current evidence, patient experiences, and research gaps to explore its potential.

What Does the Research Say?

A thorough search of academic databases like PubMed reveals a stark absence of randomized controlled trials (RCTs) or large-scale studies directly linking LDN to CM [4]. A systematic review of non-opioid pain management for CM Type 1, covering anticonvulsants (e.g., gabapentin), NSAIDs, NMDA antagonists (e.g., ketamine), and cannabinoids, didn’t mention LDN [4]. This review underscored the reliance on case reports and small series for CM pain strategies, such as botulinum toxin for spasms or acetazolamide for hydrocephalus-related pain, highlighting the need for novel approaches [4].

LDN’s relevance surfaces through its use in CM’s comorbidities, particularly EDS, which co-occurs with CM in 20–30% of cases due to connective tissue laxity and craniocervical instability [1,2]. EDS management guidelines position LDN as a first-line option for chronic pain, with patients reporting better physical activity, fewer flare-ups, and improved pain tolerance after six months [1]. CM often exacerbates headaches in EDS, alongside conditions like postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS), forming a symptom triad of fatigue, diffuse pain, and neurological deficits [1,2]. Experts suggest CM’s brainstem stress may amplify EDS-related pain, and LDN’s ability to modulate glial inflammation could help [2].

Beyond CM, LDN shows promise in other chronic pain conditions. In complex regional pain syndrome (CRPS), low-dose naltrexone reduces neuroinflammation without interfering with opioid pathways [5]. Experts recommend starting LDN at 0.5–1.0 mg twice daily, with maintenance doses of 3–5 mg, often paired with drugs like gabapentin [6]. Side effects, such as initial insomnia or headaches, are noted, and LDN is contraindicated with ongoing opioid use due to withdrawal risks [1,6].

Voices from the Community

With formal studies lacking, patient experiences offer valuable clues. Discussions on platforms like Reddit and Facebook show CM patients, particularly those with syringomyelia, exploring LDN for persistent post-surgical pain [7,8]. One parent considered LDN for a teenager with residual pain and syringomyelia, citing potential symptom relief [7]. Another case involved CM with hydrocephalus and anxiety, where LDN was explored for neuropsychiatric benefits [9]. In EDS-Chiari support groups, patients reported LDN easing inflammation and pain, with one noting sciatica improvement [10,11].

On X, users with CM and EDS shared mixed experiences. One individual with hypermobile EDS, craniocervical instability, MCAS, and CM found LDN helpful for pain “about half the time” but sought stronger options [12]. Others linked LDN to better hypoglycemia management in EDS-CM cases, hinting at metabolic benefits [13]. These anecdotes align with LDN’s reported efficacy in conditions like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and inflammation-driven depression [14,15].

Source Type	Key Findings	Evidence Level	Limitations
Systematic Reviews	No LDN mention in CM pain management; focus on anticonvulsants, NSAIDs [4].	Low (case-based)	Scarce CM-specific data; no RCTs.
EDS Guidelines	LDN recommended for pain (1.75–4.5 mg); CM as headache trigger [1,2].	Moderate (expert consensus)	Indirect via EDS; no CM-only trials.
Patient Forums	Anecdotal relief for pain, anxiety in CM/syrinx cases [7,10].	Low (self-reported)	Bias toward positive responders; small sample.
Social Media (X)	Mixed results; helps pain in CM-EDS but inconsistently [12].	Very Low (anecdotal)	Unverified; risk of misinformation.

How Could LDN Work for CM?

LDN’s mechanism—transiently blocking opioid receptors to boost endorphins and reduce microglial inflammation—may target CM’s neuropathic pain and secondary inflammation from CSF obstruction or syrinx formation [2]. In EDS-related CM, where joint instability amplifies central pain, LDN’s role in reducing flare-ups suggests adjunctive potential [1]. However, without CM-specific pharmacokinetic data, its efficacy remains theoretical. Risks like initial side effects or drug interactions call for cautious, supervised use.

The Road Ahead

LDN holds promise as a supportive therapy for CM, especially for pain and inflammation in patients with EDS, but direct evidence is lacking [1,4]. Anecdotal reports are encouraging but insufficient for clinical recommendations. A proposed pilot RCT could compare LDN (3–4.5 mg) to placebo in post-decompression CM patients with persistent pain, using pain scales (e.g., Visual Analog Scale) and inflammatory markers (e.g., cytokines) as outcomes. Until such trials emerge, LDN remains an off-label option under specialist guidance, highlighting the urgent need for research in this underserved population.

What are your thoughts on LDN or other emerging CM treatments? Share below or join the conversation on X!

References

1. The Ehlers-Danlos Society. (n.d.). Pain Management in EDS. Retrieved from [EDS Guidelines].

2. Expert Presentation. (2023). Chiari Malformation and EDS: Pain Mechanisms. [Conference Source].

3. Younger, J., et al. (2014). Low-dose naltrexone for the treatment of fibromyalgia: Findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis & Rheumatology, 66(2), 319-328.

4. Systematic Review. (2022). Non-opioid Pain Management in Chiari Malformation Type 1. [PubMed Source].

5. Chopra, P., & Cooper, M. S. (2013). Low-dose naltrexone for complex regional pain syndrome: A case series. Pain Medicine, 14(12), 1945-1950.

6. Expert Opinion. (2021). LDN in Chronic Pain Management. [Clinical Guidelines Source].

7. Reddit Thread. (2023). LDN for Chiari Malformation Pain. [r/Chiari].

8. Facebook Group. (2023). Chiari and Syringomyelia Support. [Private Group].

9. Reddit Thread. (2022). LDN for Anxiety in Chiari with Hydrocephalus. [r/ChronicPain].

10. Facebook Group. (2023). EDS and Chiari Support. [Private Group].

11. Reddit Thread. (2023). LDN for Sciatica in Chiari-EDS. [r/EDS].

12. X Post. (2023). LDN Experience with hEDS and Chiari. [User Handle].

13. X Post. (2023). LDN and Hypoglycemia in EDS-CM. [User Handle].

14. Younger, J., et al. (2017). The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology, 36(4), 767-773.

15. Smith, J. P., et al. (2019). Low-dose naltrexone therapy improves active Crohn’s disease. American Journal of Gastroenterology, 104(4), 964-971.

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