Another variable is fentanyl, the highly potent synthetic opioid that's been responsible for a rising number of overdoses in recent years. Some states have a lot of fentanyl in their drug supply, and others do not.

"We saw increases all along the Mississippi river, and I would not be surprised if that was due to an increase in the proportion of fentanyl in their drug supply," Winograd says. Deaths from fentanyl continue to rise, according to Ahmad from the CDC.

Other variations in the drug supply could contribute to the differences from state to state, says Christopher Ruhm, a professor of public policy at the University of Virginia. He notes stimulants have a different geographic spread than fentanyl, and those deaths are also on the rise.