Does low-dose naltrexone (LDN) help autoimmune diseases?

Short Answer: Low-dose naltrexone (1.5-4.5mg at bedtime) has shown promise in small trials for Crohn's disease, multiple sclerosis, and fibromyalgia through endorphin modulation and immune regulation, but large RCTs are lacking.

Evidence Level: preliminary

Detailed Answer

Naltrexone at full dose (50mg) blocks opioid receptors for addiction treatment. At low doses (1.5-4.5mg), it causes a brief opioid receptor blockade followed by a compensatory upregulation of endogenous endorphins (met-enkephalin, beta-endorphin) and opioid growth factor (OGF). This paradoxical rebound modulates immune function through OGF-OGFr signaling on T cells and macrophages. Clinical evidence: a pilot RCT in Crohn's disease (Smith et al., 2007) showed 89% response rate vs. 40% placebo. An MS trial showed reduced fatigue and improved quality of life. Fibromyalgia trials show ~30% pain reduction. LDN is inexpensive (~$1/day compounded), well-tolerated (vivid dreams and initial insomnia are common), and has a strong patient advocacy community. The lack of pharmaceutical industry funding limits large trial development.

Sources