Revisiting opioid toxicity: Cellular effects of six commonly used opioids

There is an ongoing opioid crisis in the United States where the illicit and non-medical use of prescription opioids is associated with an increasing number of overdose deaths. Few studies have investigated opioid-induced effects on cell viability, and comparative studies are limited. Here, we examine the toxicity of six commonly used opioids: methadone, morphine, oxycodone, hydromorphone, ketobemidone, and fentanyl with respect to mitochondrial and membrane function in vitro.

The opioids were tested in four different cell cultures: primary cortical cell cultures, human neuroblastoma SH-SY5Y cells, and both differentiated and undifferentiated neuroblastoma/glioma hybrid NG108-15 cells. The mitochondrial activity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the membrane integrity was assessed by measuring the leakage of lactate dehydrogenase. To compare the different opioids, the toxic dose (TD₅₀) was calculated.

The results displayed a similar trend of opioid-reduced cell viability in all four cell cultures. The most toxic opioid was methadone, followed by fentanyl, while morphine was overall ranked as the least toxic opioid displaying little to no negative impact on cell viability. The remaining opioids varied in rank between the different cell types.

This in vitro study highlights opioid-dependent variations in toxicity across all four tested cell types, with methadone emerging as the most potent opioid.