Interesting to see the dramatic rise in deaths related to substance abuse from 1996 onwards, the year Purdue Pharma introduced Oxycontin. It's especially glaring in the most impoverished parts of Appalachia.

You can play with this map to see where the changes are biggest and smallest.

Interestingly, the strip from Maryland to Georgia - which normally stands out in US political maps, due to issues of slavery and race - stands out as being one big area where deaths due to drugs or substance abuse didn't increase much at all, annually, from a relatively low start.

Is there any obvious reason for the higher death rate in the "bible belt"?

One thing I could imagine is rural exodus, leaving a higher percentage of old people.