Low-dose naltrexone (LDN) typically means 1.5 to 4.5 mg compounded capsules taken at bedtime, roughly one-tenth the standard 50 mg dose used for opioid and alcohol use disorder. The hypothesis, advanced by researchers including Bernard Bihari, is that brief opioid receptor blockade causes compensatory upregulation of endogenous endorphins and enkephalins, modulating immune function through Toll-like receptor 4 (TLR4) pathways on microglia and peripheral immune cells.
Proposed mechanisms
At standard high doses, naltrexone continuously blocks mu-opioid receptors. At low doses with short half-life, a partial block followed by rebound may increase opioid peptide tone and reduce pro-inflammatory cytokine signaling. LDN is discussed in chronic pain, fibromyalgia, Crohn's disease, multiple sclerosis, and long COVID contexts, largely off-label.
Evidence quality
RCT data exist but are heterogeneous. A 2014 Crohn's disease pilot showed benefit; fibromyalgia trials are mixed; many conditions rely on case series. LDN is not FDA-approved for inflammatory or pain indications. Patients should approach it as experimental with informed consent, not as established standard of care.
4.5 mg standard
Compounding pharmacies often titrate 1.5 mg weekly to 4.5 mg maintenance, the most common telehealth maintenance dose in CLYR's catalog. Take at night because endorphin pulse timing may align with sleep; vivid dreams are a reported side effect.
Contraindications
Patients on chronic opioids cannot use naltrexone without precipitated withdrawal. Liver disease requires caution. Pregnancy data are insufficient.
CLYR Health offers LDN 4.5mg capsules as a recovery/wellness preview SKU for patients whose providers support off-label immunomodulatory protocols.