Low-Dose Naltrexone LDN in Multiple Sclerosis MS: An Integrative Medicine Functional Medicine Perspective
- John Kim
- Jan 2
- 9 min read
Yoon Hang "John" Kim, MD, MPH
Low-Dose Naltrexone in Multiple Sclerosis: An Integrative Medicine Perspective
About Dr. Kim
Dr. Yoon Hang "John" Kim is a board-certified integrative medicine physician with over 20 years of clinical experience. He completed his integrative medicine fellowship at the University of Arizona under Dr. Andrew Weil and holds certifications in preventive medicine, medical acupuncture, and integrative/holistic medicine. Through his telemedicine practice, Dr. Kim specializes in utilizing LDN or Low Dose Naltrexone for treating autoimmune conditions, chronic pain, integrative oncology, and complex conditions including fibromyalgia, chronic fatigue, MCAS, and mold toxicity. He is the author of three books and more than 20 articles, and has helped establish integrative medicine programs at institutions nationwide.
Professional: www.yoonhangkim.com | Clinical: www.directintegrativecare.com
LDN MS Integrative Medicine Functional Medicine
Introduction
Multiple sclerosis (MS) remains one of the most challenging autoimmune disorders affecting the central nervous system, characterized by chronic inflammation, progressive demyelination, and cumulative neurological disability. For the estimated 2.8 million people living with MS worldwide, the journey involves navigating complex treatment decisions, managing unpredictable symptoms, and maintaining quality of life despite disease progression (Walton et al., 2020). While conventional disease-modifying therapies (DMTs) form the cornerstone of MS management, many patients and practitioners within integrative medicine and functional medicine are exploring complementary approaches that address the multifaceted nature of this condition.
Low-dose naltrexone (LDN), typically administered at 0.5 to 4.5 mg nightly, has emerged as one such option garnering significant attention. Originally developed at standard doses (50 mg) for opioid and alcohol dependence, naltrexone at low doses appears to exert fundamentally different pharmacological effects—shifting from sustained opioid receptor blockade to transient receptor modulation with potential immunomodulatory consequences. This article examines the current evidence base for LDN in MS, explores proposed mechanisms of action, and contextualizes its role within a comprehensive integrative medicine framework.
Understanding Low-Dose Naltrexone: Mechanisms and Rationale
The therapeutic rationale for LDN diverges substantially from its parent compound's original application. At standard doses, naltrexone provides continuous opioid receptor antagonism lasting approximately 24 hours. In contrast, low-dose naltrexone at 4.5 mg produces a brief blockade lasting only 4 to 6 hours, typically during sleep. This transient blockade triggers a compensatory upregulation of endogenous opioid production—including beta-endorphin and met-enkephalin—and may increase opioid receptor sensitivity (Brown & Panksepp, 2009). This interaction with opioid receptors also influences immune system balance, as LDN's effects on opioid pathways can modulate inflammatory responses.
From a functional medicine perspective, this mechanism is particularly relevant. Endogenous opioids play crucial roles in immune regulation, with beta-endorphin affecting natural killer cell activity, T-lymphocyte proliferation, and inflammatory cytokine production. The endorphin hypothesis suggests that many autoimmune conditions, including MS, may involve relative deficiencies in endogenous opioid tone, contributing to immune dysregulation and chronic inflammation (Zagon & McLaughlin, 2017).
Additionally, LDN appears to modulate glial cell activity within the central nervous system. Microglia and astrocytes, when chronically activated, contribute substantially to neuroinflammation and may perpetuate the inflammatory cascade seen in MS. Research suggests that LDN may attenuate this glial activation, potentially reducing the production of pro-inflammatory cytokines and neurotoxic mediators (Younger & Mackey, 2014). This dual action—peripheral immune modulation combined with central nervous system effects—aligns well with integrative medicine approaches that seek to address disease processes at multiple levels simultaneously.
Clinical Evidence: What the Research Demonstrates
Randomized Controlled Trials
The clinical investigation of LDN in MS, while still evolving, has produced several noteworthy studies.
Cree et al. (2010) conducted a pilot crossover trial examining 4.5 mg LDN in 80 patients with clinically definite MS over an 8-week period. Despite some attrition affecting statistical power, the study yielded important findings: LDN demonstrated excellent tolerability with no serious adverse events, and participants showed significant improvements in mental health-related quality of life measures. Specifically, improvements were documented in the SF-36 Mental Component Summary and the Perceived Deficits Questionnaire, suggesting potential benefits for cognitive and psychological well-being—domains that significantly impact daily functioning.
A subsequent trial by Sharafaddinzadeh et al. (2010) employed a 17-week crossover design in 96 patients with relapsing-remitting or secondary progressive MS. While confirming LDN's favorable safety profile, this study found limited benefit across most quality of life domains. However, a modest improvement in health perception scores emerged, prompting the investigators to recommend longer-duration studies.
Gironi et al. (2008) specifically examined LDN in primary progressive MS (PPMS), a subtype historically resistant to many interventions. Their Phase II pilot trial followed 40 patients over six months, demonstrating safety and tolerability alongside intriguing secondary findings: significant reduction in spasticity and elevated beta-endorphin levels, providing some mechanistic validation for the endorphin hypothesis. These results hold particular relevance for integrative medicine practitioners, as spasticity management represents a significant unmet need in progressive MS.
Beyond MS, LDN has been studied in other autoimmune and inflammatory conditions. Research in Crohn's disease has shown clinical improvement in active disease, and studies in fibromyalgia and rheumatoid arthritis suggest LDN may help modulate immune responses. These findings support LDN as a potential adjunctive option for various chronic inflammatory conditions.
Long-Term Observational Data
Observational studies provide insights into real-world effectiveness and long-term outcomes. Ludwig et al. (2016) conducted a 10-year retrospective review of patients treated with LDN, either as monotherapy or adjunctively with glatiramer acetate. Participants demonstrated stable health outcomes without exacerbation of symptoms or significant MRI changes over this extended period. The authors characterized the regimen as safe, non-toxic, and cost-effective—attributes particularly valued within functional medicine practice.
A pharmacoepidemiological analysis by Raknes et al. (2017) examined medication patterns among 341 Norwegian MS patients following LDN initiation. The study found no reduction in the use of standard DMTs or symptomatic medications after starting LDN, suggesting that patients and physicians viewed LDN as complementary rather than as a replacement for conventional therapies. This observation aligns with the integrative medicine philosophy of combining evidence-based conventional treatments with complementary approaches.
Positioning LDN Within an Integrative Medicine Framework
For practitioners of integrative medicine and functional medicine, LDN represents one component within a comprehensive approach to MS management. Rather than viewing it as an alternative to conventional DMTs, LDN may be most appropriately considered as an adjunctive therapy targeting specific symptomatic domains—particularly quality of life, mental health, fatigue, and spasticity—where conventional options may fall short.
The functional medicine model emphasizes identifying root causes of disease, supporting the body's inherent healing mechanisms, and personalizing treatment. LDN fits within this framework through its proposed action on endogenous regulatory systems rather than through direct immunosuppression. By potentially restoring opioid system balance and modulating neuroinflammation, LDN may support the body's own regulatory capacity—a principle central to functional medicine philosophy.
A comprehensive integrative approach to MS often includes dietary modifications, stress management, physical activity, and addressing environmental factors—all of which can support medical treatments and improve overall wellness. LDN can be one element within this broader therapeutic strategy.
From a practical standpoint, LDN offers several advantages: it is generally well-tolerated, relatively inexpensive (typically $35–70 monthly from compounding pharmacies), does not require monitoring bloodwork, and appears to have minimal drug interactions with most MS medications. Common side effects—vivid dreams and transient sleep disturbance during the initial weeks—are typically mild and self-limiting.
Organizational and Expert Perspectives
Major MS organizations have addressed LDN with measured positions. The National Multiple Sclerosis Society (2024) recognizes the popularity of off-label LDN use but notes that most supporting evidence remains anecdotal or derived from small trials. They advise patients to discuss LDN with their neurologists, particularly regarding potential interactions with opioid medications.
The MS Trust (2020) acknowledges reported benefits among some individuals while emphasizing that LDN is unlicensed for MS in the UK and lacks robust clinical evidence. Their guidance appropriately cautions that LDN should not replace proven disease-modifying therapies.
The LDN Research Trust (2020) provides a more optimistic assessment, summarizing practitioner reports indicating potential benefits for fatigue, pain, and spasticity. They position LDN as a complementary approach that may contribute to disease stabilization through immune modulation and endorphin enhancement, while acknowledging the need for larger confirmatory trials.
Compounding Pharmacy Considerations
Since LDN is unavailable in commercial formulations at therapeutic doses, it requires preparation by compounding pharmacies. This specialized process involves creating precisely customized doses—typically 1.5 mg to 4.5 mg—tailored to individual patient needs.
The quality of compounded LDN matters significantly. Reputable compounding pharmacies adhere to standards established by the United States Pharmacopeia (USP) and state boards of pharmacy, ensuring medications are prepared in controlled environments using pharmaceutical-grade ingredients. Patients and healthcare providers should consider pharmacies with accreditation from organizations such as the Pharmacy Compounding Accreditation Board (PCAB).
When selecting a compounding pharmacy, it's reasonable to inquire about batch testing procedures, ingredient sourcing, and established protocols. Consistent compounding practices help maintain stable therapeutic levels and minimize variability between refills—an important consideration for ongoing therapy.
Clinical Considerations and Patient Selection
For clinicians considering LDN, several practical points merit attention. Patient selection should account for current opioid use, as LDN is contraindicated in patients taking opioid medications due to potential precipitation of withdrawal. A washout period of 7 to 14 days is typically recommended before initiating LDN in patients transitioning off opioids.
Dosing typically begins at 1.5 mg nightly, with gradual titration to the target dose of 4.5 mg over 2 to 4 weeks. This approach minimizes initial side effects and allows for individual optimization. Some patients find their best response at doses below 4.5 mg, highlighting the importance of individualized titration—a hallmark of integrative medicine practice.
LDN may also benefit symptoms beyond those traditionally studied, including brain fog and chronic pain conditions such as complex regional pain syndrome. Emerging evidence suggests potential metabolic benefits, including improved insulin sensitivity, which may be relevant for patients with concurrent metabolic concerns.
"I want to highlight three real people who have beaten MS. First, Linda—founder of one of the most prominent LDN support groups—who has lived this journey herself. Second, one of my own patients whose neurologist confirmed she is now in remission; she has stopped all her MS medications through our combined integrative approach with LDN. And third, Dr. Terry Wahls, who reversed her own MS with her modified paleo diet and functional medicine principles. These aren't theoretical possibilities—these are real outcomes from real people."
Yoon Hang Kim MD
Conclusion
Low-dose naltrexone represents a promising adjunctive option within the integrative medicine toolkit for multiple sclerosis. Current evidence consistently demonstrates safety and tolerability, with some studies suggesting meaningful improvements in quality of life, mental health, and spasticity. While efficacy data remain mixed and larger randomized controlled trials are needed, LDN's favorable risk profile and low cost make it a reasonable consideration for patients seeking complementary approaches.
Within a functional medicine framework, LDN's proposed mechanism of supporting endogenous opioid and immune regulatory systems aligns with the broader philosophy of working with the body's inherent healing capacity. For patients and practitioners navigating MS treatment, LDN offers an additional option that may enhance quality of life when integrated thoughtfully with established conventional therapies.
As with all therapeutic decisions, open communication between patients and healthcare providers remains essential. Patients considering LDN should discuss it with their neurologist and integrative medicine practitioner to ensure appropriate coordination of care.
Low-Dose Naltrexone in Multiple Sclerosis: An Integrative Medicine Perspective
At Direct Integrative Care, Dr. Kim 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
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LDN Research Trust. (2020). Low dose naltrexone for MS. https://ldnresearchtrust.org/low-dose-naltrexone-ms
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Zagon, I. S., & McLaughlin, P. J. (2017). Endogenous opioids in the etiology and treatment of multiple sclerosis. In Multiple sclerosis: Perspectives in treatment and pathogenesis (pp. 125–142). Codon Publications. https://doi.org/10.15586/codon.multiplesclerosis.2017.ch8
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