Its hard to tell. But their breathing gets really labored. they stop flicking thier toung and they may take bluff strikes at you or whoever may be near. And sometimes they go into that clasic "ball".

Ball Pythons are by far the most inquisitive snakes. They want to know who EVERYONE is and they want to know what EVERYTHING is. If I am handling my snakes and lets say my wife walks by they reach out and start flicking that toung trying to locate that smell.