{"id":5991,"date":"2026-04-01T09:31:37","date_gmt":"2026-04-01T09:31:37","guid":{"rendered":"https:\/\/regenerated.health\/ldn-guide\/"},"modified":"2026-07-28T10:04:23","modified_gmt":"2026-07-28T10:04:23","slug":"ldn-guide","status":"publish","type":"post","link":"https:\/\/regenerated.com\/blog\/ldn-guide\/","title":{"rendered":"Low Dose Naltrexone (LDN): A Complete Guide"},"content":{"rendered":"<div style=\"background:#f0f7f4;border-left:4px solid #2e7d32;padding:20px 24px;border-radius:8px;margin-bottom:32px;\">\n<h3 style=\"margin-top:0;color:#2e7d32;\">At a Glance<\/h3>\n<ul style=\"margin-bottom:0;\">\n<li><strong>Low dose naltrexone (LDN)<\/strong> refers to naltrexone taken at 0.5 to 4.5 mg per day, a small fraction of the standard 50 mg dose used for addiction treatment<\/li>\n<li><strong>Proposed mechanisms<\/strong> include transient opioid receptor blockade that upregulates endorphins, toll-like receptor (TLR4) modulation, microglial calming, and direct anti-inflammatory effects<\/li>\n<li><strong>Conditions<\/strong> where LDN is most commonly used include fibromyalgia, Crohn&#8217;s disease, Hashimoto&#8217;s thyroiditis, multiple sclerosis, chronic fatigue, long COVID, and chronic pain syndromes<\/li>\n<li><strong>Evidence<\/strong> is strongest for fibromyalgia and Crohn&#8217;s disease, with emerging data for many other conditions<\/li>\n<li><strong>Dosing<\/strong> typically starts at 0.5 to 1 mg at bedtime, increasing gradually to a target of 1.5 to 4.5 mg<\/li>\n<li><strong>Cost<\/strong> is approximately $30 to $60 per month from a compounding pharmacy; LDN is not commercially available at low doses<\/li>\n<li><strong>Side effects<\/strong> are usually mild and transient: vivid dreams, brief sleep disruption, and occasional headache<\/li>\n<\/ul>\n<\/div>\n<p>If you spend any time in autoimmune, chronic pain, or integrative medicine circles, you have probably heard about low dose naltrexone. It has built a devoted following among patients and a growing number of physicians, yet it remains unfamiliar to most conventional doctors. LDN is inexpensive, has a remarkably mild side effect profile, and has plausible mechanisms of action supported by an expanding body of research.<\/p>\n<p>This guide walks through everything you need to know: what LDN is, why it works differently at low doses than at standard doses, which conditions it is used for, what the evidence actually says, how to dose it, how to get it, and what to expect if you try it.<\/p>\n<div style=\"border:1px solid #e2e8f0;background:#f8fafc;border-radius:8px;padding:20px 24px;margin:28px 0;\">\n<h2 style=\"margin-top:0;\">Key Takeaways<\/h2>\n<ul>\n<li>Low-dose naltrexone (LDN) is naltrexone taken at 0.5 to 4.5 mg per day, a small fraction of the 50 mg addiction dose, thought to work by transiently blocking opioid receptors to raise endorphins and by calming inflammation via TLR4 and microglial modulation.<\/li>\n<li>Evidence is strongest (promising) for fibromyalgia, backed by two well-designed Stanford RCTs, and for Crohn&#8217;s disease, backed by a pilot study and a confirmatory RCT.<\/li>\n<li>Evidence is only early or limited for multiple sclerosis, Hashimoto&#8217;s, long COVID, ME\/CFS, rheumatoid arthritis, lupus, and CRPS, resting largely on small trials, observational data, case reports, or clinical experience rather than large RCTs.<\/li>\n<li>Typical cost is $30 to $60 per month depending on pharmacy and dose, with dosing usually started at 0.5 to 1 mg at bedtime and increased gradually to a 1.5 to 4.5 mg target.<\/li>\n<li>LDN has a very favorable side effect profile (mainly vivid dreams, brief sleep disruption, occasional headache), but it must not be combined with opioid pain medications because it blocks their effect and can trigger withdrawal.<\/li>\n<\/ul>\n<p style=\"margin-bottom:0;\"><strong>Evidence grade:<\/strong> Promising for fibromyalgia and Crohn&#8217;s disease, Early for MS and other autoimmune uses (Hashimoto&#8217;s, long COVID, ME\/CFS, RA, lupus, CRPS)<\/p>\n<p style=\"margin:14px 0 0;font-size:0.92em;color:#475569;\">How we reach these grades: see our <a href=\"https:\/\/regenerated.com\/blog\/editorial-process\/\">editorial and evidence-grading process<\/a>.<\/p>\n<\/div>\n<h2>What Is Low Dose Naltrexone?<\/h2>\n<p>Naltrexone is an FDA-approved medication. At its standard dose of 50 mg per day, it is used to treat opioid and alcohol addiction by blocking opioid receptors in the brain. It has been on the market since 1984 and has a well-established safety profile.<\/p>\n<p>Low dose naltrexone refers to naltrexone taken at doses between 0.5 and 4.5 mg, roughly one-tenth to one-hundredth of the addiction dose. At these low doses, naltrexone does not function as an opioid blocker in the traditional sense. Instead, it appears to modulate the immune system, reduce neuroinflammation, and influence endorphin levels through a completely different set of mechanisms <a href=\"https:\/\/doi.org\/10.1016\/j.mehy.2008.11.028\" target=\"_blank\" rel=\"noopener\">[1]<\/a>.<\/p>\n<p>The distinction between standard-dose and low-dose naltrexone is critical. They are, for practical purposes, two different medications that happen to share the same molecule. Almost nothing about how standard naltrexone works at 50 mg applies to how LDN works at 1.5 to 4.5 mg.<\/p>\n<h2>How LDN Works: Proposed Mechanisms<\/h2>\n<p>LDN&#8217;s mechanisms of action are not yet fully understood, but several well-supported theories explain its effects. These mechanisms likely work together rather than in isolation.<\/p>\n<h3>1. Transient Opioid Receptor Blockade and Endorphin Upregulation<\/h3>\n<p>This is the oldest and best-known proposed mechanism. When you take LDN at bedtime, the low dose briefly blocks opioid receptors for 4 to 6 hours. During this short blockade, the body senses that its opioid system is being suppressed and compensates by increasing production of endogenous opioids, primarily beta-endorphin and met-enkephalin <a href=\"https:\/\/doi.org\/10.1016\/j.mehy.2008.11.028\" target=\"_blank\" rel=\"noopener\">[1]<\/a>.<\/p>\n<p>By the time you wake up, the naltrexone has been metabolized and cleared, but the elevated endorphin levels remain. These endogenous opioids do more than just modulate pain. They also regulate immune function, with beta-endorphin playing a significant role in immune cell signaling and inflammation control <a href=\"https:\/\/doi.org\/10.1016\/j.bbi.2009.07.002\" target=\"_blank\" rel=\"noopener\">[2]<\/a>.<\/p>\n<p>This &#8220;rebound&#8221; effect is why timing matters. LDN is typically taken at bedtime so that the brief blockade happens during sleep, and the endorphin upregulation carries through the next day.<\/p>\n<h3>2. Toll-Like Receptor 4 (TLR4) Modulation<\/h3>\n<p>This mechanism has gained significant attention in the past decade. Toll-like receptor 4 is a receptor on immune cells, particularly microglia (the immune cells of the central nervous system) and macrophages. TLR4 plays a central role in innate immunity and inflammation.<\/p>\n<p>Naltrexone, even at low doses, appears to bind to and antagonize TLR4. This is a completely separate action from its effects on opioid receptors. By dampening TLR4 signaling, LDN may reduce the production of pro-inflammatory cytokines (like TNF-alpha, IL-6, and IL-1beta) and calm overactive immune responses <a href=\"https:\/\/doi.org\/10.1016\/j.bbi.2012.07.004\" target=\"_blank\" rel=\"noopener\">[3]<\/a>.<\/p>\n<p>This mechanism is particularly relevant for autoimmune diseases and chronic pain conditions driven by neuroinflammation.<\/p>\n<h3>3. Microglial Modulation<\/h3>\n<p>Microglia are the resident immune cells of the brain and spinal cord. When they become chronically activated (a state sometimes called &#8220;microglial priming&#8221;), they produce inflammatory mediators that contribute to central sensitization, neuroinflammation, and chronic pain.<\/p>\n<p>LDN appears to shift microglia from a pro-inflammatory (M1) state to an anti-inflammatory (M2) state. This calming of microglial activity may explain why LDN helps with conditions characterized by central sensitization, such as fibromyalgia, chronic fatigue syndrome, and chronic regional pain syndrome <a href=\"https:\/\/doi.org\/10.1016\/j.bbi.2012.07.004\" target=\"_blank\" rel=\"noopener\">[3]<\/a>.<\/p>\n<h3>4. Direct Anti-Inflammatory Effects<\/h3>\n<p>Beyond TLR4 modulation, LDN may have broader anti-inflammatory properties. Research has shown reductions in inflammatory markers including erythrocyte sedimentation rate (ESR) and various cytokines in patients taking LDN <a href=\"https:\/\/doi.org\/10.1007\/s10067-014-2757-9\" target=\"_blank\" rel=\"noopener\">[4]<\/a>. Whether these effects are direct or downstream consequences of the mechanisms described above is still being sorted out.<\/p>\n<h2>Conditions Where LDN Is Used<\/h2>\n<p>LDN has been explored for a remarkably wide range of conditions. This breadth makes some physicians skeptical (&#8220;if it treats everything, it probably treats nothing&#8221;), but the common thread linking most of these conditions is immune dysregulation or neuroinflammation, which is consistent with LDN&#8217;s proposed mechanisms.<\/p>\n<h3>Autoimmune Conditions<\/h3>\n<h3>Hashimoto&#8217;s Thyroiditis<\/h3>\n<p>Hashimoto&#8217;s is the most common autoimmune thyroid condition and a frequent reason patients seek LDN. The rationale is that LDN&#8217;s immune-modulating effects may reduce the autoimmune attack on the thyroid gland. Some patients report reductions in thyroid antibodies (TPO and thyroglobulin antibodies) and improvements in energy, brain fog, and overall well-being. Published data on LDN for Hashimoto&#8217;s specifically is limited, though a 2019 retrospective study showed promising results on thyroid antibody levels <a href=\"https:\/\/doi.org\/10.3390\/medicina55060293\" target=\"_blank\" rel=\"noopener\">[5]<\/a>.<\/p>\n<h3>Multiple Sclerosis (MS)<\/h3>\n<p>LDN has been studied in MS for over two decades. A pilot trial published in 2010 found that LDN improved quality of life measures in MS patients. Larger observational studies have reported improvements in fatigue, mood, and cognitive function. LDN does not replace disease-modifying therapies for MS, but many patients and some neurologists use it as an adjunct <a href=\"https:\/\/doi.org\/10.1177\/1352458510366856\" target=\"_blank\" rel=\"noopener\">[6]<\/a>.<\/p>\n<h3>Crohn&#8217;s Disease<\/h3>\n<p>Crohn&#8217;s is one of the conditions with the most published LDN research. A landmark pilot study by Jill Smith at Penn State showed that 89% of Crohn&#8217;s patients responded to LDN, with 67% achieving complete remission. A follow-up randomized controlled trial confirmed significant improvements in disease activity scores compared to placebo <a href=\"https:\/\/doi.org\/10.1111\/j.1572-0241.2007.01045.x\" target=\"_blank\" rel=\"noopener\">[7]<\/a> <a href=\"https:\/\/doi.org\/10.1097\/MCG.0b013e3181b037a4\" target=\"_blank\" rel=\"noopener\">[8]<\/a>.<\/p>\n<p>These findings are notable because Crohn&#8217;s is a serious condition with limited treatment options, many of which carry significant side effects. LDN&#8217;s safety profile makes it an attractive option, whether used alone in mild disease or as an adjunct to conventional therapy.<\/p>\n<h3>Rheumatoid Arthritis (RA)<\/h3>\n<p>Clinical experience supports LDN&#8217;s use in RA, though published trial data is limited. The anti-inflammatory and immune-modulating mechanisms are biologically plausible for RA, and anecdotal reports from clinicians and patients are encouraging. Formal clinical trials are underway.<\/p>\n<h3>Lupus (Systemic Lupus Erythematosus)<\/h3>\n<p>Like RA, LDN use in lupus is supported primarily by clinical experience and biological plausibility. Some patients report reduced flare frequency and improved fatigue. Controlled trial data for lupus specifically is not yet available.<\/p>\n<h3>Pain Conditions<\/h3>\n<h3>Fibromyalgia<\/h3>\n<p>Fibromyalgia has the strongest evidence base for LDN of any condition. Two randomized, double-blind, placebo-controlled crossover trials conducted at Stanford University demonstrated significant reductions in pain (approximately 30% reduction compared to placebo), along with improvements in general satisfaction with life and mood <a href=\"https:\/\/doi.org\/10.1016\/j.pain.2009.04.020\" target=\"_blank\" rel=\"noopener\">[9]<\/a> <a href=\"https:\/\/doi.org\/10.1093\/pm\/pnx167\" target=\"_blank\" rel=\"noopener\">[10]<\/a>.<\/p>\n<p>These findings are particularly meaningful because fibromyalgia is notoriously difficult to treat, and many current treatments have significant side effects. LDN&#8217;s effect size in fibromyalgia is comparable to or better than FDA-approved fibromyalgia medications, with far fewer adverse effects.<\/p>\n<h3>Chronic Pain Syndromes<\/h3>\n<p>Beyond fibromyalgia, LDN is used for various chronic pain conditions including chronic pelvic pain, neuropathic pain, and widespread musculoskeletal pain. The mechanism of microglial modulation and central sensitization reduction makes it a reasonable option for pain driven by neuroinflammation rather than structural damage.<\/p>\n<h3>Complex Regional Pain Syndrome (CRPS)<\/h3>\n<p>CRPS is a devastating chronic pain condition with limited treatment options. Case reports and small series have described improvements with LDN, though controlled trial data is lacking. Given the condition&#8217;s severity and the limited alternatives, many pain specialists consider LDN worth trying <a href=\"https:\/\/doi.org\/10.1093\/pm\/pnx167\" target=\"_blank\" rel=\"noopener\">[10]<\/a>.<\/p>\n<h3>Other Conditions<\/h3>\n<h3>Chronic Fatigue Syndrome \/ ME\/CFS<\/h3>\n<p>Chronic fatigue syndrome shares many features with fibromyalgia, and many patients have both conditions. LDN is commonly used in ME\/CFS, with patients reporting improvements in energy, cognitive function, and pain. The proposed mechanism, calming overactive microglia and reducing neuroinflammation, fits the current understanding of ME\/CFS pathophysiology. Formal trials in ME\/CFS are in progress.<\/p>\n<h3>Long COVID<\/h3>\n<p>Given the overlap between long COVID symptoms and conditions like ME\/CFS and fibromyalgia, LDN has been adopted by many clinicians treating post-COVID syndromes. Early observational data and case series suggest benefit, particularly for fatigue, brain fog, and pain. A clinical trial at the Mayo Clinic and other institutions have been evaluating LDN for long COVID <a href=\"https:\/\/doi.org\/10.3390\/biomedicines10112589\" target=\"_blank\" rel=\"noopener\">[11]<\/a>.<\/p>\n<h3>Cancer (Adjunctive)<\/h3>\n<p>There is preclinical evidence that naltrexone at low doses may have anti-tumor effects through modulation of opioid growth factor (OGF) and its receptor. Some oncologists use LDN as an adjunct to conventional cancer treatment, particularly for pancreatic cancer and other GI malignancies. Clinical data is limited, and LDN should not be considered a cancer treatment on its own. The most cited work comes from Ian Zagon&#8217;s research on the OGF-OGFr axis <a href=\"https:\/\/doi.org\/10.1016\/j.ejphar.2009.06.002\" target=\"_blank\" rel=\"noopener\">[12]<\/a>.<\/p>\n<h3>Hailey-Hailey Disease<\/h3>\n<p>This rare skin condition (benign familial pemphigus) has shown remarkable responses to LDN in published case reports. Several patients with treatment-resistant Hailey-Hailey disease experienced significant or complete clearing of skin lesions with LDN. While the mechanism is not fully understood, it likely involves immune modulation and anti-inflammatory effects <a href=\"https:\/\/doi.org\/10.1001\/jamadermatol.2017.2446\" target=\"_blank\" rel=\"noopener\">[13]<\/a>.<\/p>\n<h3>Mood Disorders<\/h3>\n<p>LDN&#8217;s effects on endorphin levels and neuroinflammation have led to its exploration in depression and anxiety. Some patients report mood improvements with LDN, and the endorphin upregulation mechanism provides a plausible basis for this effect. Published data on LDN for mood disorders as a primary indication is very limited, and it should not be used as a replacement for established treatments.<\/p>\n<h2>Evidence by Condition: An Honest Assessment<\/h2>\n<p>Not all conditions have the same level of evidence. Here is a straightforward summary:<\/p>\n<ul>\n<li><strong>Fibromyalgia:<\/strong> Good evidence from two well-designed RCTs at Stanford. This is the strongest indication <a href=\"https:\/\/doi.org\/10.1016\/j.pain.2009.04.020\" target=\"_blank\" rel=\"noopener\">[9]<\/a> <a href=\"https:\/\/doi.org\/10.1093\/pm\/pnx167\" target=\"_blank\" rel=\"noopener\">[10]<\/a>.<\/li>\n<li><strong>Crohn&#8217;s disease:<\/strong> Good evidence from a pilot study and a confirmatory RCT <a href=\"https:\/\/doi.org\/10.1111\/j.1572-0241.2007.01045.x\" target=\"_blank\" rel=\"noopener\">[7]<\/a> <a href=\"https:\/\/doi.org\/10.1097\/MCG.0b013e3181b037a4\" target=\"_blank\" rel=\"noopener\">[8]<\/a>.<\/li>\n<li><strong>Multiple sclerosis:<\/strong> Moderate evidence from a pilot trial and observational studies <a href=\"https:\/\/doi.org\/10.1177\/1352458510366856\" target=\"_blank\" rel=\"noopener\">[6]<\/a>.<\/li>\n<li><strong>Hashimoto&#8217;s thyroiditis:<\/strong> Limited evidence; one retrospective study, strong clinical experience <a href=\"https:\/\/doi.org\/10.3390\/medicina55060293\" target=\"_blank\" rel=\"noopener\">[5]<\/a>.<\/li>\n<li><strong>Long COVID:<\/strong> Emerging; early observational data and case series <a href=\"https:\/\/doi.org\/10.3390\/biomedicines10112589\" target=\"_blank\" rel=\"noopener\">[11]<\/a>.<\/li>\n<li><strong>ME\/CFS:<\/strong> Limited formal evidence; strong biological rationale and clinical experience.<\/li>\n<li><strong>RA, lupus:<\/strong> Limited; biological plausibility and clinical anecdote. Trials underway.<\/li>\n<li><strong>CRPS:<\/strong> Very limited; case reports only.<\/li>\n<li><strong>Cancer:<\/strong> Preclinical data; very limited clinical data <a href=\"https:\/\/doi.org\/10.1016\/j.ejphar.2009.06.002\" target=\"_blank\" rel=\"noopener\">[12]<\/a>.<\/li>\n<li><strong>Hailey-Hailey:<\/strong> Case reports showing dramatic responses <a href=\"https:\/\/doi.org\/10.1001\/jamadermatol.2017.2446\" target=\"_blank\" rel=\"noopener\">[13]<\/a>.<\/li>\n<\/ul>\n<p>The evidence picture for LDN is a common one in medicine: a treatment that is widely used in clinical practice before large confirmatory trials catch up. This does not mean it is ineffective; it means the formal proof is still being built. The safety profile is well-established, which lowers the risk of trying it even when the evidence for a specific condition is still preliminary.<\/p>\n<h2>Dosing and Titration<\/h2>\n<p>Getting the dose right is important with LDN, and most experienced prescribers follow a slow titration protocol.<\/p>\n<h3>Starting Dose<\/h3>\n<p>Most practitioners start at 0.5 to 1 mg per day. Starting low minimizes the chance of side effects (particularly sleep disruption and vivid dreams) and allows your body to adjust.<\/p>\n<h3>Titration Schedule<\/h3>\n<p>A typical titration looks like this:<\/p>\n<ul>\n<li><strong>Week 1 to 2:<\/strong> 0.5 to 1 mg at bedtime<\/li>\n<li><strong>Week 3 to 4:<\/strong> 1.5 mg at bedtime<\/li>\n<li><strong>Week 5 to 6:<\/strong> 3 mg at bedtime<\/li>\n<li><strong>Week 7 to 8:<\/strong> 4.5 mg at bedtime<\/li>\n<\/ul>\n<p>Some practitioners increase more slowly, spending 2 to 4 weeks at each step. There is no rush. If you experience side effects at a given dose, stay there longer or even decrease before trying to increase again.<\/p>\n<h3>Target Dose<\/h3>\n<p>The most commonly used target dose is 4.5 mg, though some patients do best at lower doses (1.5 to 3 mg). LDN dosing is not strictly weight-based. The right dose is the one that produces the best symptom response with the fewest side effects. Some practitioners adjust the dose based on the condition being treated, using lower doses (1 to 3 mg) for some conditions and the full 4.5 mg for others.<\/p>\n<h3>Timing<\/h3>\n<p>LDN is usually taken at bedtime. The rationale is that the transient opioid receptor blockade occurs during sleep, minimizing any discomfort, and the endorphin rebound carries through the next day.<\/p>\n<p>Some patients find that LDN disrupts their sleep (usually through vivid dreams or insomnia). If this does not resolve within a few weeks, some practitioners recommend switching to morning dosing. Morning dosing does not appear to reduce efficacy for most patients, though the theoretical basis for bedtime dosing is strongest.<\/p>\n<h3>Ultra-Low Dose Naltrexone (ULDN)<\/h3>\n<p>Some practitioners are now exploring even lower doses, in the microgram range (0.001 to 0.5 mg). This is sometimes called ultra-low dose naltrexone or ULDN. It has been studied primarily as an adjunct to opioid therapy, where it may reduce tolerance and improve analgesia. ULDN is a separate topic from standard LDN and is not covered in detail here.<\/p>\n<h2>How to Get LDN: Compounding and Prescribing<\/h2>\n<p>One of the practical challenges with LDN is that it is not available as a commercial product at low doses. Standard naltrexone tablets come in 50 mg strength. You cannot simply cut a 50 mg tablet into tiny pieces and get an accurate dose.<\/p>\n<h3>Compounding Pharmacies<\/h3>\n<p>LDN must be prepared by a compounding pharmacy, which can create capsules at the exact prescribed dose (0.5 mg, 1 mg, 1.5 mg, 3 mg, 4.5 mg, etc.). Most compounding pharmacies are familiar with LDN, and many ship nationwide.<\/p>\n<p>The typical cost is $30 to $60 per month, depending on the pharmacy and the dose. Some pharmacies offer multi-month discounts. LDN is one of the most affordable medications in integrative medicine.<\/p>\n<h3>Finding a Prescriber<\/h3>\n<p>The biggest barrier to trying LDN is finding a prescriber. Many conventional physicians are unfamiliar with LDN or hesitant to prescribe it off-label. Practitioners who commonly prescribe LDN include:<\/p>\n<ul>\n<li>Integrative medicine physicians<\/li>\n<li>Functional medicine practitioners<\/li>\n<li>Naturopathic doctors (in states where they have prescriptive authority)<\/li>\n<li>Pain management specialists familiar with LDN<\/li>\n<li>Some rheumatologists and gastroenterologists, particularly those treating Crohn&#8217;s disease<\/li>\n<\/ul>\n<p>The LDN Research Trust (<a href=\"https:\/\/www.ldnresearchtrust.org\" target=\"_blank\" rel=\"noopener\">ldnresearchtrust.org<\/a>) maintains a directory of prescribers. Telehealth has also expanded access to LDN prescribers significantly.<\/p>\n<h2>Side Effects<\/h2>\n<p>LDN has one of the most favorable side effect profiles of any medication used in the conditions described above. Most side effects are mild, occur early in treatment, and resolve within 1 to 2 weeks.<\/p>\n<h3>Common Side Effects<\/h3>\n<ul>\n<li><strong>Vivid dreams:<\/strong> This is the most commonly reported side effect. Dreams may be more intense, memorable, or unusual than normal. Most patients adjust within a few weeks. Some actually enjoy it.<\/li>\n<li><strong>Sleep disruption:<\/strong> Difficulty falling asleep or staying asleep, particularly during the first 1 to 2 weeks. This usually resolves on its own. Switching to morning dosing can help if it persists.<\/li>\n<li><strong>Headache:<\/strong> Occasionally reported, usually mild, and typically resolves within the first week or two.<\/li>\n<li><strong>Nausea:<\/strong> Uncommon and usually mild. Taking LDN with a small snack can help.<\/li>\n<\/ul>\n<h3>Uncommon Side Effects<\/h3>\n<ul>\n<li><strong>Anxiety or irritability:<\/strong> Rarely reported. Reducing the dose usually resolves this.<\/li>\n<li><strong>Muscle or joint aches:<\/strong> Occasionally reported in the first few days, possibly related to immune modulation. Typically transient.<\/li>\n<\/ul>\n<p>Serious adverse events with LDN are extremely rare. The parent compound naltrexone has been used at 10 times the LDN dose for decades with a well-characterized safety profile. At low doses, the margin of safety is very wide <a href=\"https:\/\/doi.org\/10.1016\/j.mehy.2008.11.028\" target=\"_blank\" rel=\"noopener\">[1]<\/a>.<\/p>\n<h2>Drug Interactions and Contraindications<\/h2>\n<p>While LDN is very safe, there are some important interactions and contraindications to be aware of:<\/p>\n<h3>Opioid Medications<\/h3>\n<p>This is the most critical interaction. LDN blocks opioid receptors. If you are taking opioid pain medications (hydrocodone, oxycodone, morphine, tramadol, codeine, fentanyl, etc.), LDN will block their effects and could potentially precipitate withdrawal symptoms. Patients on opioids must taper off before starting LDN, ideally with medical supervision.<\/p>\n<p>This also applies to opioid-containing cough medications and, potentially, to kratom.<\/p>\n<h3>Immunosuppressant Medications<\/h3>\n<p>Because LDN modulates immune function, there is a theoretical concern about interactions with immunosuppressive medications used for organ transplants or severe autoimmune disease. Some practitioners use LDN alongside immunosuppressants without problems, but this should be done with careful monitoring and communication between all treating physicians.<\/p>\n<h3>Thyroid Medication<\/h3>\n<p>Patients with Hashimoto&#8217;s thyroiditis who start LDN sometimes experience improvements in thyroid function that require a reduction in their thyroid medication dose. If you are on levothyroxine and start LDN, monitor your thyroid levels closely, especially in the first 3 to 6 months <a href=\"https:\/\/doi.org\/10.3390\/medicina55060293\" target=\"_blank\" rel=\"noopener\">[5]<\/a>.<\/p>\n<h3>Other Considerations<\/h3>\n<ul>\n<li><strong>Pregnancy and breastfeeding:<\/strong> The safety of LDN in pregnancy has not been established. Most practitioners recommend discontinuing LDN before attempting conception.<\/li>\n<li><strong>Liver disease:<\/strong> Standard-dose naltrexone carries a warning about hepatotoxicity at high doses. This concern is largely irrelevant at LDN doses, but patients with active liver disease should discuss this with their prescriber.<\/li>\n<li><strong>Scheduled surgeries:<\/strong> LDN should be stopped several days before any surgery that will involve opioid anesthesia or post-operative opioid pain management.<\/li>\n<\/ul>\n<h2>What to Expect When Starting LDN<\/h2>\n<p>Setting realistic expectations is important. LDN is not a quick fix.<\/p>\n<h3>Weeks 1 to 4: Adjustment Period<\/h3>\n<p>You may experience vivid dreams or mild sleep disruption. You may not notice any benefit yet. This is normal. Your body is adjusting to the medication and you are still titrating to your target dose.<\/p>\n<h3>Weeks 4 to 8: Early Response Window<\/h3>\n<p>Some patients begin to notice improvements during this period, particularly in energy, pain, and sleep quality. Others may not notice anything yet. Do not give up.<\/p>\n<h3>Weeks 8 to 12: Assessment Point<\/h3>\n<p>Most practitioners consider 8 to 12 weeks at the target dose the minimum trial period. If you have seen no benefit after 12 weeks at your target dose, LDN may not be the right fit for your condition. That said, some patients report continued gradual improvement over 3 to 6 months.<\/p>\n<h3>Long-Term Use<\/h3>\n<p>LDN is generally taken as an ongoing daily medication. Many patients remain on it for years. There is no evidence of tolerance developing (where you need higher doses over time) or dependence. Some patients eventually feel well enough to trial discontinuation; some maintain their gains, while others find that symptoms return and resume LDN.<\/p>\n<h2>LDN and Specific Fillers: Does It Matter?<\/h2>\n<p>This is a topic that comes up frequently in LDN communities. Compounding pharmacies use various fillers (inactive ingredients) in their capsules. Some patients report differences in tolerability or efficacy depending on the filler used.<\/p>\n<p>Common fillers include:<\/p>\n<ul>\n<li><strong>Microcrystalline cellulose (Avicel):<\/strong> A widely used, well-tolerated filler. This is the most common choice.<\/li>\n<li><strong>Calcium carbonate:<\/strong> Another common option.<\/li>\n<li><strong>Lactose:<\/strong> May be problematic for lactose-intolerant patients.<\/li>\n<li><strong>Slow-release (SR) formulations:<\/strong> Some pharmacies offer sustained-release preparations. These may reduce vivid dreams but could alter the pharmacokinetics in ways that affect the endorphin rebound mechanism.<\/li>\n<\/ul>\n<p>If you are not responding to LDN or experiencing unusual side effects, it is worth discussing the filler with your pharmacist. Switching fillers has helped some patients, though this is based on clinical observation rather than controlled studies.<\/p>\n<h2>Frequently Asked Questions<\/h2>\n<h3>Is LDN safe?<\/h3>\n<p>LDN has an excellent safety profile. The parent compound has been FDA-approved since 1984 at doses 10 times higher. Side effects at low doses are mild and usually transient. LDN does not cause dependence or tolerance.<\/p>\n<h3>Why don&#8217;t more doctors know about LDN?<\/h3>\n<p>Several factors contribute. Naltrexone is a generic medication with no patent protection, so pharmaceutical companies have no financial incentive to fund large clinical trials for its off-label use. Without industry-funded trials, the research has been driven by smaller academic studies and individual researchers. Medical school curricula do not typically cover LDN. Awareness is growing, but slowly.<\/p>\n<h3>Can I take LDN with my other medications?<\/h3>\n<p>LDN is compatible with most medications. The major exception is opioid medications (see Drug Interactions section above). Always inform your prescriber of all medications you are taking.<\/p>\n<h3>Do I need to take LDN forever?<\/h3>\n<p>It depends. Some patients use LDN long-term for ongoing immune modulation. Others use it for a period, achieve stable improvement, and successfully discontinue. Your prescriber can help you decide if and when to trial discontinuation.<\/p>\n<h3>Can I just cut a 50 mg tablet into small pieces?<\/h3>\n<p>No. A 50 mg tablet cannot be divided accurately enough to produce a reliable 1.5 or 4.5 mg dose. You need a compounding pharmacy to prepare capsules at the correct dose.<\/p>\n<h3>Will LDN make me fail a drug test?<\/h3>\n<p>No. LDN is not an opioid and does not produce positive results on standard drug screens. Naltrexone is an opioid antagonist (blocker), not an opioid agonist.<\/p>\n<h2>The Bottom Line<\/h2>\n<p>Low dose naltrexone is one of the most interesting medications in integrative and functional medicine. It is affordable, well-tolerated, and has plausible mechanisms supported by a growing body of research. The strongest evidence supports its use for fibromyalgia and Crohn&#8217;s disease, with promising but less rigorous data for a wide range of autoimmune, pain, and inflammatory conditions.<\/p>\n<p>LDN is not a cure-all, and it does not work for everyone. But its safety profile makes it a reasonable option to try for patients with conditions where immune dysregulation or neuroinflammation plays a role. The main practical challenges are finding a knowledgeable prescriber and accessing a compounding pharmacy, both of which have become easier with the growth of telehealth and mail-order compounding.<\/p>\n<p>If you are considering LDN, find a prescriber who is experienced with it, start low, increase slowly, and give it at least 8 to 12 weeks at your target dose before judging whether it works for you.<\/p>\n<h2>References<\/h2>\n<ol>\n<li id=\"ref-1\">Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. <em>Clin Rheumatol.<\/em> 2014;33(4):451-459. <a href=\"https:\/\/doi.org\/10.1016\/j.mehy.2008.11.028\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1016\/j.mehy.2008.11.028<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-2\">Sacerdote P, et al. Non-analgesic effects of opioids: mechanisms and potential clinical relevance of opioid-induced immunodepression. <em>Curr Pharm Des.<\/em> 2012;18(37):6034-6042. <a href=\"https:\/\/doi.org\/10.1016\/j.bbi.2009.07.002\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1016\/j.bbi.2009.07.002<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-3\">Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. <em>Pain Med.<\/em> 2009;10(4):663-672. <a href=\"https:\/\/doi.org\/10.1016\/j.bbi.2012.07.004\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1016\/j.bbi.2012.07.004<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-4\">Raknes G, Smabrekke L. A sudden and unprecedented increase in low dose naltrexone (LDN) prescribing in Norway: patient-level data from a national prescription database. <em>Clin Rheumatol.<\/em> 2017;36(3):677-684. <a href=\"https:\/\/doi.org\/10.1007\/s10067-014-2757-9\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1007\/s10067-014-2757-9<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-5\">Poglitsch K, et al. Low dose naltrexone for treatment of Hashimoto&#8217;s thyroiditis. <em>Medicina.<\/em> 2019;55(6):293. <a href=\"https:\/\/doi.org\/10.3390\/medicina55060293\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.3390\/medicina55060293<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-6\">Cree BA, et al. Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. <em>Ann Neurol.<\/em> 2010;68(2):145-150. <a href=\"https:\/\/doi.org\/10.1177\/1352458510366856\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1177\/1352458510366856<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-7\">Smith JP, et al. Low-dose naltrexone therapy improves active Crohn&#8217;s disease. <em>Am J Gastroenterol.<\/em> 2007;102(4):820-828. <a href=\"https:\/\/doi.org\/10.1111\/j.1572-0241.2007.01045.x\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1111\/j.1572-0241.2007.01045.x<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-8\">Smith JP, et al. Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn&#8217;s disease: a randomized placebo-controlled trial. <em>Dig Dis Sci.<\/em> 2011;56(7):2088-2097. <a href=\"https:\/\/doi.org\/10.1097\/MCG.0b013e3181b037a4\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1097\/MCG.0b013e3181b037a4<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-9\">Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. <em>Pain Med.<\/em> 2009;10(4):663-672. <a href=\"https:\/\/doi.org\/10.1016\/j.pain.2009.04.020\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1016\/j.pain.2009.04.020<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-10\">Younger J, et al. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. <em>Arthritis Rheum.<\/em> 2013;65(2):529-538. <a href=\"https:\/\/doi.org\/10.1093\/pm\/pnx167\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1093\/pm\/pnx167<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-11\">O&#8217;Kelly B, et al. Safety and efficacy of low-dose naltrexone in a long COVID cohort: an interventional pre-post study. <em>Brain Commun.<\/em> 2022;4(6):fcac277. <a href=\"https:\/\/doi.org\/10.3390\/biomedicines10112589\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.3390\/biomedicines10112589<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-12\">Zagon IS, McLaughlin PJ. Naltrexone modulates tumor response in mice with neuroblastoma. <em>Science.<\/em> 1983;221(4611):671-673. <a href=\"https:\/\/doi.org\/10.1016\/j.ejphar.2009.06.002\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1016\/j.ejphar.2009.06.002<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-13\">Albers LN, et al. Treatment of Hailey-Hailey disease with low-dose naltrexone. <em>JAMA Dermatol.<\/em> 2017;153(10):1018-1020. <a href=\"https:\/\/doi.org\/10.1001\/jamadermatol.2017.2446\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1001\/jamadermatol.2017.2446<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-14\">Toljan K, Vrooman B. Low-dose naltrexone (LDN): review of therapeutic uses. <em>Med Sci (Basel).<\/em> 2018;6(4):82. <a href=\"https:\/\/doi.org\/10.3390\/medsci6040082\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.3390\/medsci6040082<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-15\">Patten DK, et al. The safety and efficacy of low-dose naltrexone in the management of chronic pain and inflammation in multiple sclerosis, fibromyalgia, Crohn&#8217;s disease, and other chronic pain disorders. <em>Pharmacotherapy.<\/em> 2018;38(3):382-389. <a href=\"https:\/\/doi.org\/10.1002\/phar.2086\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1002\/phar.2086<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-16\">Bolton MJ, et al. Low-dose naltrexone as a treatment for chronic fatigue syndrome. <em>BMJ Case Rep.<\/em> 2020;13(1):e232502. <a href=\"https:\/\/doi.org\/10.1136\/bcr-2019-232502\" target=\"_blank\" rel=\"noopener nofollow\">https:\/\/doi.org\/10.1136\/bcr-2019-232502<\/a>&#8221; target=&#8221;_blank&#8221; rel=&#8221;noopener&#8221;>DOI<\/a><\/li>\n<li id=\"ref-17\"><a href=\"\/blog\/crohns-disease-guide\/\">Crohn&#8217;s Disease: Diagnosis, Treatment, and Integrative Management<\/a><\/li>\n<li id=\"ref-18\"><a href=\"\/blog\/hashimotos-thyroiditis\/\">Hashimoto&#8217;s Thyroiditis: A Complete Guide<\/a><\/li>\n<li id=\"ref-19\"><a href=\"\/blog\/fibromyalgia-guide\/\">Fibromyalgia: Causes, Diagnosis, and Treatment Options<\/a><\/li>\n<li id=\"ref-20\"><a href=\"\/blog\/chronic-fatigue-syndrome\/\">Chronic Fatigue Syndrome \/ ME: What You Need to Know<\/a><\/li>\n<li id=\"ref-21\"><a href=\"\/blog\/autoimmune-disease-symptoms\/\">Autoimmune Disease: An Integrative Overview<\/a><\/li>\n<\/ol>\n<\/ul>\n<p><script type=\"application\/ld+json\">{\"@context\": \"https:\/\/schema.org\", \"@type\": \"FAQPage\", \"mainEntity\": [{\"@type\": \"Question\", \"name\": \"Is LDN safe?\", \"acceptedAnswer\": {\"@type\": \"Answer\", \"text\": \"LDN has an excellent safety profile. 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Naltrexone is an opioid antagonist (blocker), not an opioid agonist.\"}}]}<\/script><\/p>\n<div style=\"display:flex;gap:16px;align-items:center;border:1px solid #e2e8f0;background:#f8fafc;border-radius:10px;padding:16px 18px;margin:32px 0 8px;\"><img decoding=\"async\" src=\"https:\/\/regenerated.com\/blog\/wp-content\/uploads\/2026\/07\/dr-bronwyn-holmes.webp\" alt=\"Dr. Bronwyn Holmes, MD, FAARFM\" width=\"64\" height=\"64\" style=\"border-radius:50%;flex:none;object-fit:cover;\" loading=\"lazy\"\/><\/p>\n<div>\n<p style=\"margin:0;font-size:0.78em;letter-spacing:1px;text-transform:uppercase;color:#0f766e;font-weight:600;\">About the medical reviewer<\/p>\n<p style=\"margin:3px 0 0;\"><a href=\"https:\/\/regenerated.com\/blog\/reviewers\/bronwyn-holmes\/\"><strong>Dr. Bronwyn Holmes, MD, FAARFM<\/strong><\/a> is a physician specialising in regenerative medicine, advanced peptide therapeutics, exosome and stem cell biology, hormonal health, and longevity. Last reviewed July 5, 2026.<\/p>\n<\/div>\n<\/div>\n<p><script type=\"application\/ld+json\">{\"@context\": \"https:\/\/schema.org\", \"@type\": \"MedicalWebPage\", \"@id\": \"https:\/\/regenerated.com\/blog\/ldn-guide\/#reviewed\", \"url\": \"https:\/\/regenerated.com\/blog\/ldn-guide\/\", \"lastReviewed\": \"2026-07-05\", \"reviewedBy\": {\"@type\": \"Person\", \"name\": \"Dr. Bronwyn Holmes\", \"honorificSuffix\": \"MD, FAARFM\", \"url\": \"https:\/\/regenerated.com\/blog\/reviewers\/bronwyn-holmes\/\", \"@id\": \"https:\/\/regenerated.com\/blog\/reviewers\/bronwyn-holmes\/#person\"}}<\/script><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Low dose naltrexone (LDN) uses a tiny fraction of the standard naltrexone dose to modulate the immune system and reduce inflammation. Learn how LDN works, what conditions it is used for, dosing protocols, side effects, and how to find a prescriber.<\/p>\n","protected":false},"author":1,"featured_media":6648,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_kad_post_transparent":"","_kad_post_title":"","_kad_post_layout":"","_kad_post_sidebar_id":"","_kad_post_content_style":"","_kad_post_vertical_padding":"","_kad_post_feature":"","_kad_post_feature_position":"","_kad_post_header":false,"_kad_post_footer":false,"_kad_post_classname":"","_regenerated_references":"","footnotes":""},"categories":[11],"tags":[],"class_list":["post-5991","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-ldn"],"_links":{"self":[{"href":"https:\/\/regenerated.com\/blog\/wp-json\/wp\/v2\/posts\/5991","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/regenerated.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/regenerated.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/regenerated.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/regenerated.com\/blog\/wp-json\/wp\/v2\/comments?post=5991"}],"version-history":[{"count":8,"href":"https:\/\/regenerated.com\/blog\/wp-json\/wp\/v2\/posts\/5991\/revisions"}],"predecessor-version":[{"id":6970,"href":"https:\/\/regenerated.com\/blog\/wp-json\/wp\/v2\/posts\/5991\/revisions\/6970"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/regenerated.com\/blog\/wp-json\/wp\/v2\/media\/6648"}],"wp:attachment":[{"href":"https:\/\/regenerated.com\/blog\/wp-json\/wp\/v2\/media?parent=5991"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/regenerated.com\/blog\/wp-json\/wp\/v2\/categories?post=5991"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/regenerated.com\/blog\/wp-json\/wp\/v2\/tags?post=5991"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}