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represents the highest-risk window for relapse without treatment support Hypothalamic-pituitary-adrenal axis suppression: reduced testosterone and cortisol production causing hormonal dysregulation and sexual dysfunction Immune system dysregulation: opioid-induced inhibition of natural killer cell and T-cell function increasing vulnerability to bacterial and viral infection Neonatal abstinence syndrome (NAS): opioid-dependent newborns born to mothers who used M365 during pregnancy require medically supervised withdrawal management in a neonatal intensive care unit Chronic high-dose M365 use elevates hepatic enzymes (AST, ALT) through acetaminophen accumulation, progressing to hepatic fibrosis in individuals with concurrent alcohol use disorder or pre-existing liver disease

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Perhaps most important among these are the Toll-like Receptors (TLR) including TLR-2 (348,349), TLR-4 (350), TLR-6 (351), TLR-7 (352), and TLR-9 (352)