LDN Q&A: 1. AM or PM? 2. Insomnia 3. Side Effects 4. Worse on LDN 5. Dose Increase? 6. Lowest Dose? 7. Complex Conditions - MCAS, POTS, hEDS

LDN Q&A: Your Questions Answered

A Supportive Guide for the LDN Support Group

Download your free LDN Primer Booklet from www.LDNSupportGroup.org

January 18 2026

Important Disclaimer

This guide shares information based on published research and community experiences. It is not medical advice. LDN is a prescription medication that should only be used under the supervision of a qualified healthcare provider. Always consult your doctor before starting, adjusting, or stopping any medication.

Part 1: Quick FAQ

These are the most common questions we see in our community. For deeper explanations, see the comprehensive guide in Part 2.

Q1: Should I take LDN in the morning or at night?

There's no universal "right" answer. Nighttime is traditionally recommended, but if you experience insomnia, morning dosing may work better for you. Some people feel drowsy taking it in the morning initially, but this often improves. Try what feels right and give any change at least 1-2 weeks.

Q2: I'm having terrible insomnia on LDN. What should I do?

Insomnia is one of the most common side effects, especially at night. Options include: switching to morning dosing, reducing your dose, or if you just started, giving it 1-2 weeks to see if it improves. If insomnia persists despite these adjustments, discuss with your prescriber.

Q3: Should I push through side effects or reduce my dose?

It depends on severity. Mild effects (slight sleep changes, vivid dreams) often resolve in 1-2 weeks. Moderate to severe effects (significant insomnia, bad headaches, vertigo, irritability) are signals to reduce your dose. If symptoms are getting worse rather than better, back off.

Q4: I tolerated LDN fine at first, but now I'm getting worse the longer I take it. Why?

This pattern happens to some people. LDN's effects can be cumulative, and what your body tolerated initially may become too much over time. Your underlying condition may also have changed. If you've tried reducing doses and breaks without success, discuss with your provider whether to stop.

Q5: How slowly should I increase my dose?

Standard protocols suggest reaching 4.5 mg in 2-4 weeks, but this is too fast for many people. If you're sensitive or severely ill, consider 2-4 week intervals between increases—or even longer. Some very sensitive patients need months between dose changes. Patience is key.

Q6: What's the lowest dose I can try?

Clinical protocols recognize ultra-low doses in the microgram range (1-2 mcg), very-low doses (0.01-0.5 mg), and traditional low doses (1-4.5 mg). If you're highly sensitive, starting at 0.5 mg or lower and titrating very slowly may help. Discuss options with your prescriber.

Q7: Does it matter which compounding pharmacy I use?

Some people report differences between pharmacies. If you're sensitive, you might try a formulation without silica or other common fillers. There isn't definitive research on this, but some individuals with MCAS or sensitivities notice improvements with cleaner formulations.

Q8: Is it normal to feel worse before feeling better?

Some people experience a brief adjustment period with mild side effects that resolve. However, feeling significantly worse that doesn't improve over 2-4 weeks isn't necessarily "normal"—it may mean the dose is too high for you. Listen to your body.

Q9: What if LDN just doesn't work for me?

Research suggests about one-third of people don't respond to standard LDN therapy. This isn't a personal failure—it may mean your condition works through different pathways, or your endorphin reserves are depleted. Some people try again successfully later after addressing other health factors.

Q10: I have POTS, hEDS, or MCAS. Any special considerations?

These complex conditions often require extra care. Start at very low doses and titrate extremely slowly. For MCAS, LDN alone may not be sufficient—complementary treatments like mast cell stabilizers are sometimes added. Work closely with a provider experienced in these conditions.

Part 2: Comprehensive Guide

This section provides in-depth information based on clinical experience and published research. Remember, everyone's journey with LDN is unique.

Understanding How People Respond to LDN

One of the most important things to understand is that not everyone responds to LDN in the same way. Clinical experience and research suggest that people generally fall into three categories:

Category 1: LDN Works Well on Its Own

For some people, LDN alone produces meaningful and sustained improvement. These individuals typically have adequate baseline endorphin reserves, moderate symptom severity, and good overall functional capacity. Research in fibromyalgia has shown response rates around 57-65%, with some studies demonstrating significant pain reduction compared to placebo (Younger et al., 2013; Toljan & Vrooman, 2023).

Category 2: LDN Helps, But Isn't Enough Alone

In more complex situations, LDN plays an important supporting role but may not achieve the full results someone is hoping for on its own. Conditions that often fall into this category include mast cell activation syndrome (MCAS), Long COVID, chronic inflammatory response syndrome (CIRS), and complex regional pain syndrome. In these cases, LDN may calm the immune system enough to make other treatments more effective and better tolerated (Kim, 2025).

Category 3: Non-Responders

Some people simply don't respond to LDN at any dose. This may relate to severely depleted endorphin reserves, genetic variations in opioid receptor function, or conditions that aren't primarily mediated by the pathways LDN affects. If you've given LDN a thorough trial without benefit, this doesn't mean you've failed—it may simply mean LDN isn't the right tool for your particular situation.

The Endorphin Reserve Concept

A key concept in understanding LDN therapy is what clinicians call "endorphin reserve." LDN works partly by temporarily blocking opioid receptors, which triggers your body to produce more endorphins. But if your body's endorphin-producing capacity is already depleted from prolonged illness, this mechanism may not work as expected.

Healthcare providers experienced with LDN often assess functional capacity to estimate endorphin reserve. They may ask about duration of illness, sleep quality, energy levels, recovery time from setbacks, and ability to perform daily activities. People with very low functional capacity often need a much gentler approach to starting LDN (Kim, 2025).

Dosing Strategies: One Size Does NOT Fit All

This is perhaps the most important section for our community members who are struggling with side effects.

Standard Dosing

The commonly cited protocol of starting at 1.5 mg and working up to 4.5 mg over 2-4 weeks works well for people with moderate illness and good functional capacity. However, many people in health support communities like ours have more complex situations that require a different approach.

Low and Ultra-Low Dosing

The LDN Research Trust recognizes three dosing categories: ultra-low dose (microgram range, 1-2 mcg), very-low dose (0.01-0.5 mg daily), and the traditional low dose (1-4.5 mg, sometimes up to 10 mg). At very low doses, naltrexone may work through different mechanisms, potentially acting more gently on the system through a phenomenon called hormesis (LDN Research Trust, 2024).

For people who are severely ill, have low functional capacity, or are highly sensitive, starting at 0.5 mg or even lower and increasing very slowly may be essential. Some sensitive individuals may need 2-4 weeks between dose increases, while the most sensitive may need 1-3 months between adjustments. This is a marathon, not a sprint.

When Side Effects Persist at Low Doses

If you're experiencing persistent side effects even at very low doses, this may indicate that your endorphin reserves are significantly depleted. Options include dropping to an even lower dose, extending the time between dose increases, or discussing with your healthcare provider whether LDN is appropriate for your current situation. Sometimes stepping away and addressing other aspects of health first allows people to try LDN again successfully later.

Morning vs. Night: Finding What Works for You

The timing question comes up constantly in our group, and for good reason—it can make a significant difference in tolerability.

Nighttime dosing is traditionally recommended because LDN's brief opioid receptor blockade coincides with the body's natural endorphin release during sleep. Many people do well with this approach. However, insomnia and vivid dreams are among the most commonly reported side effects, and taking LDN at night can make these worse for some people.

Morning dosing works better for those who experience sleep disruption. Some people report feeling drowsy or "out of it" when first switching to morning dosing, but this often improves as the body adjusts. There's no definitive research saying one time is universally better—it's about finding what works for your body.

If nighttime dosing is causing severe insomnia, switching to morning is absolutely worth trying. Give any timing change at least a week or two before deciding if it's working.

Common Side Effects and What They May Mean

Side Effect	What It May Indicate	Suggested Approach
Insomnia / vivid dreams	Common with nighttime dosing	Try morning dosing; may improve with time
Headaches	Adjustment period or dose too high	Often resolves in 1-2 weeks; reduce dose if severe
Fatigue / drowsiness	Body adjusting; may indicate dose sensitivity	Consider timing change; reduce dose if persistent
Irritability / mood changes	Possible dose sensitivity	Reduce dose; ensure adequate rest
Nausea / GI upset	Common early effect	Take with food; usually improves
Vertigo / dizziness	May indicate dose too high	Reduce dose; titrate more slowly
Increased pain (temporary)	Some experience initial flare	May resolve; discuss with provider if persists

Most side effects are temporary and resolve within the first few weeks. However, if side effects persist or worsen despite dose adjustments, this is important information to share with your healthcare provider.

When You Initially Tolerated LDN But Now Can't

This is a pattern we see repeatedly in our community, and it can be deeply frustrating. You started LDN without problems, built up to a certain dose, and then symptoms appeared that get worse the longer you stay on it—even when you drop back down.

Several things may explain this pattern. First, LDN's effects are cumulative over time, so what your body tolerated at first may become too much as levels build. Second, your underlying condition may have changed, affecting how you respond to LDN. Third, there may be interactions with other factors in your health that weren't present initially.

If you've tried reducing the dose, taking breaks, and using the every-other-day method without success, it may be time to have a candid conversation with your prescriber about whether to discontinue—at least for now. Stopping LDN is not a failure. Some people return to it successfully later when other aspects of their health have been addressed.

Should I Power Through Side Effects or Reduce My Dose?

This is one of the most common questions we receive, and the answer depends on the severity and type of side effects.

Mild, tolerable side effects (slight sleep changes, mild headache, vivid but not disturbing dreams) often resolve within 1-2 weeks as your body adjusts. If the side effects aren't significantly impacting your quality of life, it may be reasonable to stay at your current dose and give it more time.

Moderate to severe side effects (significant insomnia, severe headaches, marked irritability, vertigo, blurred vision) are signals from your body that the current dose is too much. In these cases, reducing the dose or pausing is generally the wiser choice. There's no benefit to "pushing through" if it means feeling miserable.

A practical approach: if side effects are getting progressively worse rather than improving, back off. If they're stable or slowly improving, you might give it more time.

Special Considerations for POTS, hEDS, and MCAS

Many members of our community are managing complex overlapping conditions like postural orthostatic tachycardia syndrome (POTS), hypermobile Ehlers-Danlos syndrome (hEDS), and mast cell activation syndrome (MCAS). These conditions often require extra care when starting LDN.

For MCAS in particular, LDN may be helpful but often isn't sufficient on its own. Clinical protocols sometimes combine LDN with mast cell stabilizers like ketotifen or cromolyn sodium (Weinstock et al., 2018). If you have MCAS and are struggling with LDN tolerance, discussing these complementary approaches with your healthcare provider may be worthwhile.

People with these conditions often benefit from starting at the lowest possible doses and titrating extremely slowly—sometimes over many months rather than weeks.

Does the Compounding Formulation Matter?

Some community members report significant differences in how they tolerate LDN from different compounding pharmacies or with different inactive ingredients (excipients). While there isn't robust research on this topic, clinical experience suggests that some people are sensitive to fillers like silica, certain dyes, or other additives.

If you're highly sensitive or have MCAS, working with a compounding pharmacy that can prepare LDN with minimal excipients may be worth exploring. Common requests include formulations without silica, dye-free preparations, and hypoallergenic fillers.

When to Consider Stopping LDN

LDN isn't right for everyone, and recognizing when it's not working is just as important as giving it a fair trial. Consider discussing discontinuation with your healthcare provider if: side effects persist despite multiple dose adjustments and timing changes, you've tried for several months without any perceived benefit, side effects significantly outweigh any benefits, or your symptoms are progressively worsening on the medication.

Stopping LDN is generally straightforward since it doesn't cause physical dependence. Some people notice temporary changes when stopping, but these typically resolve within a few days.

A Final Word of Support

Managing chronic health conditions is challenging, and trying to optimize LDN therapy can feel like solving a puzzle with many pieces. Please remember that your experience is valid, even if it doesn't match what others describe. What works beautifully for one person may not work for another, and that's okay.

Always work with a healthcare provider who understands LDN and can help guide your decisions. This community is here to share experiences and support each other, but personalized medical guidance is essential.

Be patient with yourself. Be willing to adjust. And know that whether LDN ends up being part of your health toolkit or not, you're on a path toward understanding your body better.

LDN Support Group

About the Author: 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 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.

Professional: www.yoonhangkim.com 

Clinical: www.directintegrativecare.com

This document is for educational purposes only and does not constitute medical advice. Individual results vary. Please consult your healthcare provider for personalized guidance.

References

Bruun, K. D., Christensen, R., Amris, K., et al. (2021). Low-dose naltrexone for the treatment of fibromyalgia: Protocol for a double-blind, randomized, placebo-controlled trial. Trials, 22(1), 804. https://doi.org/10.1186/s13063-021-05804-6

Kim, Y. H. (2018). Ultra low dose naltrexone, micro dosing [Conference presentation]. LDN Research Trust 2018 Conference.

Kim, Y. H. (2025). Low-dose naltrexone primer: A clinical guide to optimizing LDN therapy. Direct Integrative Care. https://www.directintegrativecare.com

LDN Research Trust. (2024). Dosing information for prescribers. https://ldnresearchtrust.org

Toljan, K., & Vrooman, B. (2023). Efficacy of low-dose naltrexone and predictors of treatment success or discontinuation in fibromyalgia and other chronic pain conditions. Biomedicines, 11(4), 1087. https://doi.org/10.3390/biomedicines11041087

Weinstock, L. B., Brook, J. B., Myers, T. L., & Goodman, B. (2018). Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment. BMJ Case Reports, bcr2017221405. https://doi.org/10.1136/bcr-2017-221405

Yang, J., Shin, K. M., Do, A., et al. (2023). The safety and efficacy of low-dose naltrexone in patients with fibromyalgia: A systematic review. Journal of Pain Research, 16, 1017-1023. https://doi.org/10.2147/JPR.S397456

Younger, J., Noor, N., McCue, R., & Mackey, S. (2013). Low-dose naltrexone for the treatment of fibromyalgia: Findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial. Arthritis & Rheumatism, 65(2), 529-538. https://doi.org/10.1002/art.37734

Younger, J., Parkitny, L., & McLain, D. (2014). The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology, 33(4), 451-459. https://doi.org/10.1007/s10067-014-2517-2