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LDN briefly blocks opioid receptors for 4–6 hours. Your body responds by increasing production of endorphins—your natural pain-relieving and mood-regulating compounds. It also calms overactive immune responses by modulating glial cells and reducing neuroinflammation. This dual action is why LDN helps such a wide range of conditions.
Standard naltrexone tablets are manufactured at 50mg for addiction treatment. LDN requires doses between 0.5mg–4.5mg, which aren't commercially available and must be custom compounded.
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Low Dose Naltrexone (LDN) refers to naltrexone taken at doses between 0.5mg and 4.5mg—roughly 1/10th of the standard 50mg dose approved for opioid and alcohol addiction. At these low doses, naltrexone behaves differently, acting as an immune modulator rather than a sustained opioid blocker.
LDN is prescribed off-label for autoimmune conditions (MS, Crohn's, Hashimoto's, rheumatoid arthritis), chronic pain (fibromyalgia, CRPS), and inflammatory conditions including MCAS and Long COVID. Research is ongoing, but clinical use has grown significantly based on its favorable safety profile and patient-reported outcomes.
Because naltrexone is only commercially available as a 50mg tablet, LDN must be prepared by a compounding pharmacy in custom doses and formulations—capsules, tablets, liquids, or topical creams depending on patient needs.
Most patients start low (0.5mg–1.5mg) and titrate up over several weeks. Effects typically take 1–3 months to notice.
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Endorphin UpregulationLDN blocks opioid receptors briefly (4–6 hours), triggering a rebound increase in endorphins and enkephalins—your body's natural pain relievers and mood regulators. This is why LDN is typically taken at bedtime, aligning with your body's overnight endorphin production cycle.
Immune ModulationLDN calms overactive glial cells (immune cells in the central nervous system), reducing pro-inflammatory cytokines. This helps shift the immune system away from the chronic inflammatory state seen in autoimmune conditions.
TLR4 AntagonismLDN blocks Toll-Like Receptor 4 (TLR4) on microglia, reducing neuroinflammation—a key driver of chronic pain and fatigue.
Why Low Dose MattersAt the standard 50mg dose, naltrexone blocks opioid receptors continuously. At low doses, the blockade is temporary—just enough to trigger the therapeutic rebound without long-term receptor suppression.
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LDN is prescribed off-label for a wide range of conditions:
Autoimmune Conditions: Multiple sclerosis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, Hashimoto's thyroiditis, lupus, psoriasis, celiac disease
Chronic Pain Conditions: Fibromyalgia, complex regional pain syndrome (CRPS), chronic fatigue syndrome
Neurological Conditions: Parkinson's disease (adjunctive), autism spectrum disorder (research ongoing)
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MCAS (Mast Cell Activation Syndrome), Long COVID, certain cancers (adjunctive/experimental), depression, anxiety
Starting Dose: 0.5mg–1.5mg at bedtime
Titration: Increase by 0.5mg–1.5mg every 1–2 weeks as tolerated
Target Dose: Most commonly 3mg–4.5mg at bedtime (some conditions may use lower maintenance doses)
Timing: Usually taken at bedtime to align with the body's natural endorphin release cycle (though some patients do better with morning dosing)
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Titration: Increase by 0.5mg–1.5mg every 1–2 weeks as tolerated
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Common (usually transient, first 1–2 weeks):
Less Common:
Most side effects resolve with continued use or dose adjustment. Taking in the morning instead of evening can help with sleep disturbances.
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