Naltrexone is used in the treatment of alcohol dependence in doses of 50 mg naltrexone hydrochloride per day (in the USA also in the treatment of opioid dependence, both oral and injectable), in combination with bupropion in the treatment of obesity. In low doses (1-5 mg per day) it specifically binds to TLR-4 receptors, where it acts antagonistically. It has an anti-inflammatory effect through microglia cells. Its low doses reduce the synthesis of tumor necrosis factor (TNF)-α and interferon-β. Low-dose naltrexone (LDN) is a modulating tool of the neuroimmune axis, which interferes with the neuroendocrine axis. Opioid growth factor (OGFr) signaling is transiently increased. LDN acts stereoselectively. Administration of (+)-naltrexone does not affect opioid signaling, hut only TLR-4 signaling. It is beneficial in the treatment of fibromyalgia, Crohn's disease, multiple sclerosis, tumors, chronic benign pemphigus (Hailey-Hailey disease) and Gulf War Illness. Ultra-low doses of naltrexone (ULDN) are less than 1 μg. The analgesic effect is mediated by the second messenger filamin A It is mainly used in postoperative control of analgesia. Doses between 1 μg and 1 mg are very low doses of naltrexone (VLDN), which has been used as adjunct treatment for boosting tolerability of opioid-weaning methadone ta per.

Key words: Low-dose naltrexone – D-naltrexone – L-naltrexone – TLR-4 – filamin A – OGFr