The title is drawn from one of the longest interstate highways in the US, routing from southern Florida to the northern tip of Michigan. Ohio is one of six states through which 75 passes, and is known to be a main distribution route for contraband into Cincinnati and Dayton.
On the final day of principal photography, the footage amounted to a total of exactly 75 takes.
The entire cast is comprised of Greater Cincinnati- or Ohio-based actors, with the exception of a few cast members who came in from Louisville to appear in the project.
Never is a needle shown actually penetrating a vein on camera.
Sahil Sharma conceived the idea of an interconnected narrative about the Cincinnati opiate crisis, but expanded it with Joe Zappa, who developed the script over the course of 10 drafts. Actor-producer Kip Bennett contributed a few key scenes to the shooting script, such as Leslie Mitchell's climactic scenes in the bathtub and with her children.