The fight scene between Saul (James Franco) and Carol (Rosie Perez) was for the most part improvised. Because of this, Franco was worried that he would hurt Perez and would ask her for permission to do certain things during the fight. In the end, Perez actually did get hurt and got a bruise after Franco accidentally bit her too hard on the thigh, but Perez didn't tell him until after filming was done so he wouldn't feel bad.
When James Franco smashes the bong over Danny McBride's head, it was supposed to be a fake, break-away bong so McBride could take part in the stunt. However, it was filled with some water and when Franco actually smashed it, McBride was mildly hurt.
As he is handing Dale some guns, Red (Danny McBride) says, "Ted Jones messed with the wrong melon farmers." This is a reference to the common network television practice of dubbing over "swear" words with less "objectionable" words or terms that have a similar sound and length - even if the replacement words don't really make sense in the context of the movie. "Melon Farmers" was used most famously as the dub for "Mother F***ers" in the network television version of the Die Hard series of movies (in which lead character John McClane's famous catchphrase, "Yippie-kai-yay, Mother F***ers!," became "Yippie-kai-yay, Melon Farmers!").
During a July 2008 interview with the Orange County Register about Pineapple Express, the interviewer told Seth Rogen and James Franco that he prepared for the interview by watching the classic stoner comedy Fast Times at Ridgemont High (1982) the night before. When he asked Rogen and Franco if they prepared likewise before making this film, Franco said he prepared by making out with Spicoli (a reference to his having shot Milk (2008), in which he and Sean Penn play lovers).
The place where Saul and Dale are held hostage is where the beginning of the movie takes place underground. In the back of the room you can see the water suit in which the people used when testing the effects of marijuana.
James Franco's character carries a Taconic High School duffle bag in almost every scene of the movie. Taconic High School is a public school in Pittsfield, Mass. The schools mascots are "The Braves" and the colors are green and yellow.