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.
Initially, Michael Cera was not actually slapping Rihanna's butt, but rather making the motion and stopping right before touching her. As a result of the enclosed space forcing awkward camera angles, the scene was not working on camera because it looked too fake. Eventually, Cera asked Rihanna if he could actually slap her butt. She said yes, but on the condition that she be allowed to really smack him across the face each time. Cera agreed, but Rihanna neglected to mention, much to Cera's chagrin, she would be slapping Cera harder with each take.