What is the proper protocol for titrating Low Dose Naltrexone (LDN)?
Explore titration schedules and maintenance dosing for low‑dose naltrexone (LDN) across listed conditions: inflammatory bowel disease (IBD), long COVID‑19, cancer-adjunctive use, autoimmune disease (including thyroiditis), and chronic pain
Summary Table
| Condition | Starting Dose | Escalation Schedule | Typical Maintenance Dose |
|---|---|---|---|
| IBD (Crohn’s / UC) | Usually 4.5 mg/day (some weight-based starts at ~0.1 mg/kg) | If titrated: weekly small increments to 4.5 mg | 4.5 mg/day (evening) |
| Long COVID | 1 mg → 2 mg | Month‑by‑month; may escalate up to 3–4.5 mg or split dosing | 1–3 mg/day (some escalate) |
| Chronic pain / autoimmunity | 1.5 mg/day | Increase to 3 mg in ~1 week, then to 4.5 mg over next week(s) | 4.5 mg/day |
| Thyroiditis (Hashimoto) | 0.25 mg/day | Increase 0.25‑0.5 mg weekly to 1.5–3 mg, then up to 4.5 mg | 1.5–4.5 mg/day (supervised) |
| Cancer (experimental) | 3 mg/day | Titrate to 4–4.5 mg/day if tolerated, often adjunct therapy | 4–5 mg/day (very experimental) |
Why do we recommend this LDN titration schedule & dosing?
Inflammatory Bowel Disease (Crohn’s disease / ulcerative colitis)
- Dosing: Start 1.5 mg/day for ~1 week, then 3 mg/day for ~1–2 weeks, then 4.5 mg/day as maintenance; assess response at ~8–12 weeks.
- Titration: Clinical trials typically start directly or quickly escalate to 4.5 mg without formal titration. Some weight-based protocols (especially pediatric) begin lower (~0.1 mg/kg up to ~4.5 mg/day) (PMC).
- Evidence:
- In adults with refractory Crohn’s disease, 4.5 mg daily for 12–16 weeks significantly reduced CDAI scores; 67% achieved clinical remission and 88% improved by 70‑point decline versus placebo (~40%) (PMC).
- In cohorts including ulcerative colitis, ~74.5% reported subjective improvement; remission rates ~25% (PMC).
- Side effects: Mild and transient—vivid dreams, insomnia, GI symptoms—rarely leading to discontinuation (PMC).
Long COVID‑19 / Post‑COVID Syndrome
- Titration & dosing: One retrospective real-world series reported starting at 1 mg/day in month 1, increasing to 2 mg/day in month 2; most patients received 1–3 mg/day total (PMC).
- Maintenance: Commonly stays in that 1–3 mg/day range; some individuals later escalate (e.g. up to 9 mg split dosing) under physician guidance for symptom improvement .
- Outcomes: After two months, participants in this cohort had improvement in pain, fatigue, sleep, cognition, and activities of daily living, with good tolerability (PMC).
- Mechanisms and future studies: LDN may reduce pro-inflammatory cytokines like IL‑6, TNF‑α via immune modulation and microglial effects. Ongoing controlled trials are underway (PMC).
Chronic Pain / Autoimmune‑Related Pain (e.g. fibromyalgia, CRPS, MS)
- Maintenance dose: Typically 4.5 mg/day, usually at bedtime to leverage opioid receptor rebound effect (Clin Rheumatol).
- Titration schedules: Clinically, some adopt a gradual escalation—starting at 1.5 mg/day for a week or month, then moving to 3 mg/day, then to 4.5 mg/day as tolerated.
- Evidence: A scoping review found consistent benefit in chronic centralized pain conditions across small trials; one comparative study with doses <10 mg/day over ≥1 month showed significant improvement in pain and function (PEG scores) (PMC).
Cancer‑Adjunctive Use
- Dosing: Most human reports and case studies use 3–5 mg/day, typically at 4.5 mg daily.
- Titration: Start low (e.g. 3 mg), then increase to 4–4.5 mg if tolerated and desired; some case reports include higher experimental doses (up to ~5 mg) or combination protocols with vitamin D, propranolol, α‑lipoic acid (MDPI).
- Evidence: Preclinical data suggest LDN may suppress tumor progression in cervical and colon cancer via PI3K/AKT/mTOR pathway modulation. Clinical trials in glioma and advanced cancers have been limited or inconclusive to date (PubMed).
Autoimmune Disease & Thyroiditis (e.g. Hashimoto’s)
- Dosing: Conventional dosing ~4.5 mg/day, but in hypothyroid (Hashimoto’s) patients, expert guidance suggests ultra-low starting doses (0.25 mg/day) when initiating LDN to avoid rapid shifts in thyroid hormone needs (CancerChoices).
- Titration: Increase by ~1 mg per week toward 1.5–4.5 mg depending on tolerance; slower titration for sensitive individuals .
- Considerations: LDN may modulate autoimmunity and reduce autoimmune inflammation; close monitoring of thyroid function is essential to adjust levothyroxine dosage promptly
Other suggestions:
For sensitive patients (e.g. thyroiditis / with risk of hormone shift):
- Start 0.25 mg/day; increase by 0.25–0.5 mg per week until 1.5–3 mg/day, then continue increasing to 4.5 mg/day as tolerated.
Key Considerations
- Time to effect: Most benefits accrue gradually over 6–12 weeks, though some report symptom improvement earlier (~4–8 weeks) (PMC, Wikipedia).
- Monitoring: Particularly for thyroiditis patients—watch for signs of over-replacement as immune modulation may alter TSH levels.
- Adverse effects: Typically mild—vivid dreams, insomnia, headache, GI upset—usually self-limited and often resolve within weeks; lower starting dose and slower escalation improves tolerance (PMC).
- Off-label status: None of these indications are FDA-approved for LDN; use under physician supervision with compounding support if necessary.
Clinical Note
Your physician can tailor the titration based on sensitivity, past opioid use (avoid if opioids used within ~7–10 days) and condition severity. Routine lab monitoring (e.g. thyroid function, inflammatory markers) is advisable, particularly in autoimmune and IBD contexts.
Choosing a Trusted Low Dose Naltrexone (LDN) Compounding Pharmacy
Even if a doctor was willing to prescribe naltrexone in its commercially available form for a non-label usage, imagine the difficulty of splitting a 50 mg pill into a 1/10 or 1/100 piece. That’s where working with a reputable compounding pharmacy comes into play, and HDRx pharmacists are LDN experts that practitioners and patients trust.
As Low Dose Naltrexone continues to gain recognition for its potential in chronic pain, inflammation, and autoimmune conditions, HDRx remains committed to providing Michigan’s patients and healthcare providers with high-quality, custom-compounded LDN.
HDRx stands out as Michigan’s preferred LDN compounding pharmacy for several reasons:
- Expertise and Experience: With decades of experience in compounding medications, HDRx’s pharmacists possess the knowledge and skills necessary to compound LDN at the highest level.
- Quality Assurance: HDRx is proud to hold accreditation from the Pharmacy Compounding Accreditation Board (PCAB), a testament to its commitment to maintaining the highest quality standards in compounding.
- Collaboration with Healthcare Providers: HDRx works closely with doctors to ensure compounded LDN prescriptions are optimized for each patient’s therapeutic needs, fostering a collaborative approach to patient care.
- Patient-Centric Care: Understanding the challenges patients face, HDRx prioritizes personalized service, from consultation through to medication delivery, ensuring a seamless, supportive healthcare experience.
- Various Dosage Forms: Patients are prescribed LDN in different dosage forms to best suit their individual needs. LDN is commonly prescribed in capsules, oral liquid, sublingual drops, and topical cream depending on the prescriber’s preference.
We value innovation, quality, and patient outcomes. As the medical landscape evolves, so too must the approach to managing complex health issues.
HDRx’s dedication to advancing medication therapies, evidenced by its PCAB accreditation and longstanding collaboration with healthcare professionals, positions it as a leader in compounding pharmacy services in Michigan, as well as serving/shipping to OH, IN, IL, IN, WI, MN, FL with a doctor’s prescription.
For more information on how Low Dose Naltrexone compounded by HDRx can be integrated into patient care plans, and to explore the potential benefits it may offer, contact HDRx today. Together, we can navigate the path to better health.
