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An estimated 3-12% of people treated with opioids for chronic pain will develop an addiction or abuse with negative consequences.(12) Approximately 8.6 million Americans reported misusing prescription opioids in 2023.(13) People who develop tolerance or dependence to prescription opioids may transition to illegally produced opioids, such as a fentanyl

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It must be noted that the osmotic pressure adjustment in the control group should be made by adding mannitol or another suitable organic solute to the medium, because these are biocompatible and non-toxic, making it a suitable choice for adjusting osmotic pressure without interfering with the biological processes under study [183]