Low Dose Naltrexone (LDN)
Clinical overview, dosing guidance, and the critical opioid contraindication.
⚠️ CRITICAL SAFETY INFORMATION
If you take any opioid medication — including for surgery, dental work, injury, or as‑needed for breakthrough pain — LDN is not safe to combine with opioids. Even at low doses, naltrexone will block the effect of opioid pain medications and can precipitate withdrawal in people who are opioid‑dependent.
Tell every healthcare provider (dentists, surgeons, emergency staff) that you are on LDN. For planned procedures requiring opioids, LDN must be discontinued in advance – your prescriber will advise timing.
What Is LDN?
Naltrexone is an opioid receptor antagonist approved at 50 mg for alcohol/opioid use disorder. Low‑dose naltrexone (1.5–4.5 mg) is used off‑label for chronic pain and inflammatory conditions. At low doses, it transiently blocks opioid receptors, leading to a paradoxical upregulation of endorphins and anti‑inflammatory effects.
Indications with Evidence
- Fibromyalgia: Several small RCTs show significant pain reduction (Younger & Mackey, Pain Med 2013;14(8):1176-85).
- Crohn’s disease: Open‑label studies suggest reduced disease activity.
- Multiple sclerosis: Limited evidence for improved quality of life.
- Complex regional pain syndrome (CRPS): Case series support use.
- Neuropathic pain, rheumatoid arthritis, and other autoimmune conditions – emerging evidence.
Dosing and Titration
Typical starting dose: 1.5 mg once daily at bedtime (to minimise daytime sleepiness). Increase by 1.5 mg every 2–4 weeks as tolerated, up to 4.5 mg daily. Some patients benefit from 3 mg or 6 mg. Compounding allows precise capsules in any strength.
Side Effects and Monitoring
Common but usually mild and transient: vivid dreams, insomnia, headache, nausea, fatigue. Most resolve within 1–2 weeks. Persistent side effects may respond to dose adjustment. LDN may take 8–12 weeks to show full benefit.
Contraindications and Interactions
- Absolute contraindication: concurrent use of any opioid (including tramadol, codeine, and opioid‑containing cough/cold preparations).
- Caution in pregnancy/lactation (limited data).
- May interact with immunosuppressants – theoretical, but few clinical reports.
For prescribers: LDN is off‑label. Ensure patients sign informed consent discussing the opioid contraindication and expected time to response. Provide patients with a wallet card stating they use LDN and cannot receive opioids.
References: Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone. Pain Med 2013; Parkitny L, Younger J. Reduced pro-inflammatory cytokines after eight weeks of low-dose naltrexone for fibromyalgia. J Pain Res 2017; Smith JP, et al. Low-dose naltrexone therapy improves active Crohn’s disease. Am J Gastroenterol 2007.