By RRM Academy Reviewed by Dr. Naomi Whittaker, MD, Board-Certified OBGYN, MIGS, NFPMC, FCI Updated July 26, 2026

Low-dose naltrexone (LDN) is naltrexone (an opioid antagonist) used at sub-therapeutic doses, far below the standard dose prescribed for opioid or alcohol dependence. At low doses, transient opioid receptor blockade prompts a compensatory rise in the body's own endorphin production. Researchers have proposed additional immune-modulating mechanisms, including effects on macrophage activity, that may reduce pro-inflammatory cytokines such as TNF-alpha and IL-6, though this pathway is not yet fully established. Clinical trials have studied this immune-modulating effect in chronic inflammatory conditions including multiple sclerosis and fibromyalgia.¹² Some RRM clinicians consider LDN an adjunct in patients with suspected immune-mediated implantation failure, clinical endorphin deficiency, or endometriosis-associated immune dysregulation. Its use for these indications is off-label. Clinicians considering LDN should evaluate the individual patient's immune profile and reproductive history. This entry does not include a specific dosing protocol; consult an RRM clinician.

Cited in this entry

Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. Annals of Neurology. https://pubmed.ncbi.nlm.nih.gov/20695007/
Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis & Rheumatism. https://pubmed.ncbi.nlm.nih.gov/23359310/

This content is for educational purposes only and does not constitute medical advice. Consult an RRM clinician or healthcare provider for guidance specific to your situation.