Chronic morphine use causes feedback inhibition of endogenous opioid synthesis, which further leads to opioid dependence and withdrawal.[6] Opioid agonists have been shown to decrease the expression of proenkephalin messenger RNA (mRNA).[7] On the other hand, opioid antagonists increase the expression of proenkephalin mRNA or enkephalin peptides in some cell types. The gene discussed is PENK; the disease is opiate dependence.