Although the exact mechanisms by which circadian hormone melatonin attenuates certain adverse effects of chronic opioid use are still unknown, a reduction in pro‐inflammatory and pain‐associated receptor genes, upregulation of the Kcnip3 gene (potassium voltage‐gated channel interacting protein 3; Kcnip3 which plays a role in the regulation of pain sensitivity and anxiety‐ and depression‐like behaviors103), and enhanced levels of antioxidative enzymes have been proposed.100. Here, KCNIP3 is linked to major depressive disorder.