Peter Fonda, Dennis Hopper, and Jack Nicholson engaged in a group LSD trip to prepare to be in the film.
Roger Corman also took LSD before starting the film, figuring he could not make a film about LSD without trying it himself. He had a good experience, and had to ask others what a "bad trip" was like in order to incorporate one into the film.
Jack Nicholson based the screenplay on his own experience of taking LSD under controlled laboratory conditions, as well as his divorce from his then-wife Sandra Knight.
Bruce Dern wanted nothing to do with the drug culture, and had to ask director Roger Corman what LSD was in order to prepare for his role in the film.
According to Bruce Dern, Jack Nicholson wrote the part of John in the film for himself, but Roger Corman would not agree to Nicholson playing the role and chose Dern instead.