Grant County, New Mexico
Grant County is a bit less than 4000 square miles (half the size of Wales) of desert, mountains, and spectacular wilderness inhabited by about 30,000 people, roughly 6000 of whom live in the largest town, Silver City. Several smaller towns, mostly former mining towns, dot the area. Silver City is another former mining town, with a small college, a tourist industry, and a hint of artistic post-hippiedom. Out in the wild are more refugees from civilization, including a few actual ranchers.
47% of all deaths of persons between the ages of 15 and 44 in Grant County are caused by drug overdoses. I'm not sure that that is the worst in the US, but if not, it's close.
The national map (by counties) and story at the link are illuminating and depressing. Rural and urban whites are the main victims.