Jamie (Michael Cera) is a boorish, insensitive college student travelling in Chile who leaves a path of chaos wherever he goes. He and his friends are planning on taking a road trip north to experience a legendary shamanistic hallucinogen called the San Pedro cactus. In a fit of drunkenness at a wild party, Jamie invites an eccentric woman - a radical spirit named Crystal Fairy (Hoffmann) - to come along. What is meant to be a devil-may-care journey becomes a battle of wills as Jamie finds himself locking horns with his new travelling companion. But on a remote, pristine beach at the edge of the desert, the magic brew is finally imbibed, and the true adventure begins.