If you manage to make Update() take a "very long time" (like >3s) in play mode, then it's almost impossible to exit the play mode since the "busy" dialog keeps on popping up. "The problem is that if, and when, it pops up, and if your Update() takes too long every frame, you have absolutely no way to exit play mode. The only option is to task kill Unity".

Forum thread: https://forum.unity.com/threads/application-updatescene-when-modifying-textures.944113/#post-6180003