Major clinical evidence on the use of low-dose naltrexone in the treatment of cancer: a systematic review

Introduction: Opioid receptors are groups of receptors (γ-, κ-, δ-, and ζ-opioid receptors) that are widely distributed in nerve cells in the brain, spinal cord, and digestive tract. Naltrexone is a type of general opioid receptor antagonist. It has been used to treat chronic pain syndrome, autoimmune diseases, and cancer at a dose of 5 mg/day, which is generally called low-dose naltrexone (LDN). Objective: It was to analyze the pharmacological functions of low-dose naltrexone, especially in anti-inflammation and immunoregulation, and its therapeutic potential against cancer. Methods: The research and development of the work were carried out from June to July 2024 in the Scopus, PubMed, Science Direct, and Scielo databases, using scientific articles from the last 15 years, following the PRISMA rules. The quality of the studies was based on the GRADE and AMSTAR2 instruments, and the risk of bias was assessed using the Cochrane instrument (Funnel Plot). Results and Conclusion: Fifteen studies were included in the systematic review out of 30. Most studies showed homogeneity in their results, with X2=94.5%>50%. Low-dose naltrexone has immunomodulatory and therapeutic effects. Low-dose naltrexone regulates the production of inflammatory cytokines, influencing the level of endogenous opioid peptides in the body. Furthermore, low-dose naltrexone has an antitumor effect and can modulate the neuroblastoma tumor response, delaying the onset and reducing the incidence rate of tumors, significantly decreasing tumor volume and weight, and DNA synthesis in cancer.