Exploring the Potential Role of Low-Dose Naltrexone LDN in Seizure Management: Emerging Evidence from Preclinical and Preliminary Clinical Studies - Integrative Functional Medicine San Antonio TX
- John Kim
- Dec 18, 2025
- 3 min read
Exploring the Potential Role of Low-Dose Naltrexone in Seizure Management: Emerging Evidence from Preclinical and Preliminary Clinical Studies
Edited by Yoon Hang Kim MD MPH
Low-dose naltrexone (LDN), typically administered at doses of 1–5 mg daily, represents an off-label application of a medication originally approved for opioid and alcohol dependence at higher doses (50 mg). Recent investigations have explored its potential anticonvulsant properties, primarily through modulation of neuroinflammation, glial activity, and opioid receptor signaling. These effects are thought to arise from transient blockade of toll-like receptor 4 (TLR4) on microglial cells, leading to reduced proinflammatory cytokine release and attenuation of excitotoxic pathways implicated in epileptogenesis.
Preclinical research in animal models has provided the foundational evidence for these effects. In zebrafish larvae modeling Dravet syndrome (scn1Lab mutants) and pentylenetetrazole (PTZ)-induced seizures, naltrexone significantly reduced abnormal locomotion and seizure-like behavior. Similar anticonvulsant activity was observed in mouse models, including decreased seizure-like events in acute brain slices, reduced duration and frequency of PTZ-induced convulsive seizures, and complete prevention of post-traumatic seizures following traumatic brain injury (TBI). In the TBI model, naltrexone also mitigated neuroinflammation (e.g., reduced IL-1β, TNFα expression), microgliosis, neurodegeneration, and oxidative stress markers, while preserving white matter integrity.
Human evidence remains limited but encouraging. A small case series of pediatric patients with intractable epilepsy reported substantial reductions in seizure frequency—some achieving seizure-free status—along with electrophysiological improvements on electroencephalogram (EEG) after adjunctive LDN therapy. These observations align with hypotheses that LDN's immune-modulating properties may interrupt neuroinflammatory cascades contributing to refractory seizures.
Despite these promising findings, significant caveats exist. No large-scale randomized controlled trials have confirmed efficacy or established optimal dosing for seizure disorders. Higher doses of naltrexone or combinations (e.g., with bupropion) are associated with increased seizure risk, potentially due to lowered seizure threshold in vulnerable individuals. Rare reports of seizures linked to standard-dose naltrexone underscore the need for caution.
In conclusion, while preclinical data robustly support anticonvulsant and neuroprotective roles for naltrexone, and preliminary human observations suggest clinical potential, LDN cannot currently be recommended as a standard therapy for seizures or epilepsy. Its use should be confined to supervised clinical settings, prioritizing established antiepileptic drugs. Future rigorous trials are essential to delineate efficacy, safety, and mechanisms in human populations.
For More Information, Join FB LDN Support Group: https://www.facebook.com/groups/2927649837416056
About The Author
At Direct Integrative Care, Dr. Yoon Hang Kim MD is dedicated to guiding you on your path to wellness through a deeply personalized and supportive approach. We focus on integrative medicine, looking beyond symptoms to uncover the root causes of chronic conditions and develop a treatment plan tailored specifically to your unique health journey. By combining compassionate care with innovative therapies, our goal is to empower you with the knowledge and tools needed to achieve lasting health. We invite you to explore our website to learn more about how our patient-centered practice can help you find balance and vitality.
Yoon Hang Kim MD
Integrative & Functional Medicine Physician
Virtual Practice Serving IA, IL, MO, FL, GA, and TX
References
Abokrysha, N. T., Kishk, N. A., Nawito, A. M., & Mounir, N. (2021). Effect of low-dose naltrexone on Egyptian children with intractable epilepsy: A case series study. Neurology India, 69(6), 1781–1784. https://doi.org/10.4103/0028-3886.333523
Rodriguez, S., Sharma, S., Tiarks, G., & Glykys, J. (2024). Neuroprotective effects of naltrexone in a mouse model of post-traumatic seizures. Scientific Reports, 14, Article 13507. https://doi.org/10.1038/s41598-024-63942-8
Sturgeon, M. L., Langton, R., Sharma, S., Cornell, R. A., Glykys, J., & Bassuk, A. G. (2021). The opioid antagonist naltrexone decreases seizure-like activity in genetic and chemically induced epilepsy models. Epilepsia Open, 6(3), 528–538. https://doi.org/10.1002/epi4.12512
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