Well, this was a pleasant surprise.
WHEN it works, since Picodrive is very fast (although less accurate than Genesis Plus GX) it can (should) be used with Run Ahead at 2 frames. This removes the input lag in a lot of Mega Drive games!
There are some games with 3 fps of input lag, and games that are a 30 fps, witch basically doubles the problem (Chakan for example I think it has 3 real frames of input lag + 3 of nothing because of the framerate). But all in all this is a total game changer.
You can bind one key to the “Frameadvance” option and check for yourself with/without.