Jamie (Michael Cera) is in Chile on a non-stop drug binge, with the ultimate goal of trying a shamanistic hallucinogen called the San Pedro Cactus. He takes a road-trip with his Chilean roommate and his two brothers, with the goal of buying this elusive cactus and taking it on the beach. However, the night before they leave, Jamie- in the midst of a coke binge, invites another American tourist, an eccentric young lady who calls herself the Crystal Fairy (Gaby Hoffmann). When she joins them, her and Jamie immediately lock horns- a situation made even worse once they finally get their hands on the San Pedro cactus.