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.