Should You "Push Through" LDN Side Effects?
Why Well-Meaning Advice in Online Communities Can Backfire
By Yoon Hang Kim, MD, MPHBoard-Certified Preventive Medicine | Integrative Medicine Residential Fellowship, University of Arizona | Functional Medicine Scholarship Recipient
I recently saw a question in an online LDN community that made me pause. A patient was experiencing significant side effects at a moderate dose, and several well-meaning members were encouraging them to "push through" and increase their dose anyway. "It will work," they assured. "You just have to stick with it."
After prescribing low-dose naltrexone for over two decades and presenting at multiple LDN Research Trust conferences, I've seen this advice play out many times—and I've watched it fail patients who might otherwise have found relief at a different approach.
The short answer to whether you should "push through" bad side effects is: No—at least not without understanding why this advice contradicts both published research and clinical best practices.
The Problem with One-Size-Fits-All Advice
The standard LDN protocol that most people encounter calls for starting at 1.5mg and titrating up to 4.5mg over two to four weeks. This works beautifully for many patients. But here's what the published research actually shows: the optimal dose varies dramatically between individuals, ranging from as low as 0.1mg to as high as 6mg or more.
A 2024 observational study published in the Journal of Pain Research found that "the effective doses are widely distributed, and no dose is most often the maximally effective dose." The researchers concluded this "supports the utility of a titration protocol to establish the [maximally effective dose]."
In other words, there's no magic number. Some patients achieve profound relief at 2mg and lose that benefit if they push higher. Others need 6mg. And approximately one-third of patients don't respond to standard protocols at all—not because LDN doesn't work for them, but because they need a fundamentally different approach.
Understanding the Endorphin Reserve Problem
LDN works, in part, by briefly blocking opioid receptors, which triggers a rebound effect that increases the body's production of endorphins. This mechanism assumes there's enough reserve capacity in the system to respond to that stimulus.
But what happens when someone is severely ill, chronically depleted, sleeping poorly, and functioning at a fraction of their capacity? Their endorphin reserves may be so depleted that a standard dose doesn't trigger the intended rebound—it simply overwhelms an already exhausted system.
This is why I assess functional capacity before starting LDN. I ask patients: How long have you been sick? Do you achieve restorative sleep? What's your baseline energy throughout the day? How quickly do you recover from setbacks? Can you work, exercise, or perform daily activities?
Patients with severely depleted endorphin reserves—those who are very ill or have very low functional capacity—often require a fundamentally different starting point than the standard 1.5mg.
What the LDN Research Trust Actually Recommends
The LDN Research Trust's official 2024 dosing guidelines for prescribers explicitly address this issue. For CFS/ME patients, they state: "CFS/ME patients often experience flu-like symptoms and may need slower titration. If exacerbation of symptoms, decrease dose until able to tolerate, then titrate accordingly."
Notice the guidance isn't to "push through." It's to decrease the dose and try again later.
The Bateman Horne Center, a leading ME/CFS research and treatment facility, echoes this: "In more sensitive patients, a slower titration may be preferred... In some patients with side effects, lowering the dose for a month or so and then again trying to titrate upward can be an effective method."
And the American Fibromyalgia Syndrome Association advises that if side effects persist, "you can drop down to a 3mg dose and these side effects will usually go away."
Research on Severely Ill Patients
A 2019 study on LDN in ME/CFS published in Fatigue: Biomedicine, Health & Behavior provided crucial insight: "The most severely ill (bedbound) patients had the greatest likelihood and severity of adverse symptoms associated with LDN initiation. In those patients, LDN therapy should be introduced in markedly lower doses and the dose titrated slowly."
The study found that 73.9% of ME/CFS patients reported a positive treatment response to LDN—but achieving that response required individualized approaches. Some patients needed doses well below 4.5mg. Some needed much slower titration schedules.
Weill Cornell Medicine's Division Chief for Pain Management starts patients at 1.5mg and titrates from there—but importantly, "some people need less." One ME/CFS specialist, Dr. Susan Levine, starts some patients "as low as 0.1 to 0.5mg" due to concerns about sensitivity in this population.
The "Low and Slow" Philosophy
A review in Practical Pain Management described the approach used in their clinical study: "A 'low and slow' approach to titration of LDN dose was used, and patients were verbally counseled that, vis-à-vis LDN therapy, 'more is not necessarily better.'"
That phrase deserves emphasis: more is not necessarily better.
This contradicts the well-meaning forum advice to keep pushing higher. Some patients achieve their best results at 2mg, 3mg, or even sub-milligram doses. Pushing past their optimal dose doesn't improve outcomes—it can actually cause them to lose the benefits they might have achieved at a lower dose.
Experienced compounding pharmacists report: "We have also seen where someone will titrate up too quickly for their body and miss the positive results."
What Patient Experience Actually Shows
If you look beyond the cheerleading in some online communities, you'll find patients who found success with patience and dose reduction—not by pushing through.
One patient with ME shared her experience on the Health Rising forums: "I'm super sensitive to meds and supps, even by ME standards... I started on 0.25mg and had all the side effects—nausea, diarrhea, vivid dreams, sweats, aches and pains, sore glands, agitation, insomnia... I left it 4-6 weeks before increasing by 0.25mg."
Her outcome? She eventually found her "sweet spot" at 3.5mg—not the standard 4.5mg. When she tried 3.75mg, "the side effects didn't go away, particularly the agitation." She's been stable and benefiting at 3.5mg for over two years.
Another patient on the Phoenix Rising forums reported: "I had quite substantial anxiety on 0.25mg of it. Tried to push through for 2 weeks, but it didn't get any better." This patient experienced heart palpitations and a "wired feeling" that never resolved despite pushing through.
The lesson? Pushing through worked for neither of these patients. What worked was finding the right dose for their individual physiology.
The Three Categories of LDN Response
In my clinical experience, patients fall into three distinct categories when it comes to LDN therapy:
Category 1: LDN as Sufficient Therapy. For some patients, LDN alone produces profound and sustained improvement. These patients typically have adequate baseline endorphin reserves, moderate disease severity, and good overall functional capacity. Standard protocols work well for them.
Category 2: LDN as Necessary but Not Sufficient. In complex cases—mold toxicity, cancer, MCAS, Long COVID, CRPS, chronic Lyme—LDN plays a vital role but cannot achieve remission on its own. For these patients, LDN serves as one component of a multimodal treatment strategy.
Category 3: Non-Responders to Standard Protocols. Some patients simply don't respond to standard LDN dosing. This may relate to severely depleted endorphin reserves, genetic variations in opioid receptor function, or conditions not primarily mediated by the pathways LDN modulates. These patients may need microgram dosing, ultra-low-dose approaches, or alternative strategies entirely.
A Better Approach
Instead of "pushing through," consider this evidence-based approach:
1. Start appropriately low. For standard patients, 1-1.5mg is reasonable. For sensitive patients, CFS/ME patients, or those with depleted functional capacity, consider 0.5 mg or even lower. THIS NEEDS TO BE ASSESSED AND INDIVIDUALIZED.
2. Titrate slowly. Standard protocols increase every 1-2 weeks. Sensitive patients may need 2-4 weeks between increases. The most sensitive may need 1-3 months between adjustments.
3. If side effects persist, drop the dose. Don't push through. Decrease until tolerable, stabilize, then try a slower titration later.
4. Find your optimal dose—not the "standard" dose. Your optimal dose might be 2mg, 3mg, or even microgram-level. The goal isn't to reach 4.5mg; it's to find what works for your unique physiology.
5. Give it adequate time. Experts recommend 2-3 months at your optimal dose before assessing whether LDN is working. Approximately 12% of patients don't experience benefit until after three months.
- Communicate with your physician - if possible, work with an LDN Expert.
Common Claims vs. Reality
The Bottom Line
LDN is a powerful tool in the integrative medicine toolkit, but it's not a one-size-fits-all therapy. The advice to "push through" bad side effects contradicts official guidelines from the LDN Research Trust, published research on sensitive patient populations, and clinical best practices from experienced prescribers.
If you're struggling with LDN side effects, the answer isn't necessarily to push harder. It might be to step back, reduce your dose, stabilize, and then try a slower, more individualized approach. Working with a physician experienced in LDN who understands these nuances can make the difference between treatment failure and meaningful improvement.
Online communities offer valuable support and shared experience, but medical advice—even well-intentioned advice—should be weighed against the evidence. In this case, the evidence is clear: patience and individualization outperform pushing through.
About the Author
Dr. Yoon Hang Kim MD is a board-certified preventive 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 using LDN (Low Dose Naltrexone) to treat 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.
Consulting, Professional Education, Speaking/Writing Engagement: www.yoonhangkim.com
99-Membership-Based Integrative, Functional, Metabolism, and LDN Focused Telemedicine: www.directintegrativecare.com
LDN Advocacy and Education: www.LDNSupportgroup.com
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Selected References
LDN Research Trust. Dosing Information for Prescribers. 2024.
Polo O, et al. Low-dose naltrexone in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Fatigue: Biomedicine, Health & Behavior. 2019.
Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014;33(4):451-459.
Effective Doses of Low-Dose Naltrexone for Chronic Pain – An Observational Study. J Pain Res. 2024.
Bateman Horne Center. Low-Dose Naltrexone (LDN) – A Note to Providers. 2024.
McKenzie-Brown AM, et al. Low-Dose Naltrexone (LDN) for Chronic Pain at a Single Institution: A Case Series. J Pain Res. 2023.
Kim YH. Ultra Low Dose Naltrexone, Micro Dosing. LDN Research Trust Conference. 2018.
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Yoon Hang Kim, MD, MPH
Board-Certified Preventive Medicine | Integrative & Functional Medicine
Direct Integrative Care | www.directintegrativecare.com
University of Arizona Integrative Medicine Fellowship Graduate
Institute of Functional Medicine Scholarship Recipient
