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The Endogenous Opioid System: Role and Dysfunction Caused by Opioid Therapy. The endogenous opioid system is comprised of a wide array of receptors and ligands that are present throughout the central and peripheral nervous system, the gastrointestinal tract, and the immune system. This explains the multitude of physiological functions it is responsible for including analgesia, mood regulation, and modulation of the stress response. It also plays a pivotal role in modulating the brain's reward center with behavioral and social implications on mood disorders and addiction. Exogenous opioid therapy hijacks the endogenous system and alters its functions contributing to an imbalance that is responsible for the pathogenesis of several disease states.