<p>Morphine has been a widely used drug for pain management and anesthesia in clinical settings for centuries and is also a drug of abuse. Its illicit use by individuals with substance use disorders has resulted in numerous brain-related complications. The immunopharmacology of morphine is highly complex, necessitating a deeper understanding of its interactions with brain regions involved in learning and memory. Autophagy is a conserved physiological recycling process that degrades cytoplasmic organelles and proteins, repurposing their components for cellular function. However, recent studies indicate that morphine exposure disrupts autophagic processes, contributing to many morphine-associated complications. This article highlights recent advancements in understanding the interplay between morphine and autophagy. By exploring this intricate relationship, we aim to enhance our knowledge of morphine-associated complications and autophagy dysregulation, potentially improving the management of morphine use disorder and related conditions, thereby promoting healthier outcomes.</p> Graphical Abstract <p></p>