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Both animal and human studies show a significant bidirectional relationship between the circadian system and opioid effects. Opioids can perturb circadian rhythms, and perturbation of the circadian rhythms can aggravate opioid\u2010mediated adverse effects. These bidirectional interactions may attenuate the outcomes of long\u2010term opioid therapy when not considered. A better understanding of the potential mechanisms underlying these interactions may be essential for more effective management of opioid\u2010induced adverse effects. This review highlights the association between circadian rhythms and opioid\u2010induced hyperalgesia, dependence, and withdrawal, and the possible role of the dopaminergic, serotoninergic, and noradrenergic systems, redox state, and stress in this association. 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