Seth Rogen said that he was shocked by how much the actors would insult each other. According to him, Jonah Hill and James Franco, in particular, seemed to go at each other the hardest. At one point, he felt like he had to intervene and remind them that they are actually friends and like each other.
Director Evan Goldberg created a game for himself during filming. The goal of the game was to get as many cast members as possible to say, "No, I can't do that," or get them to refuse to do something. According to Goldberg, the only people he was not able to break were James Franco and Seth Rogen.
According to Seth Rogen, the plot his character suggests in the movie, when he is asked what Pineapple Express 2 would be about, is actually his real-life idea for a Pineapple Express (2008) sequel.
The main cast took significant pay cuts, in order to help Seth Rogen and Evan Goldberg save money for the budget.