In this article, ontogenetic and phylogenetic causes of drug abuse and links to human emotional development are considered. Some evolutionary perspectives (e.g. that under certain conditions, consumption of otherwise toxic alkaloids may confer both physical and cultural advantages) are reviewed. As described in the ‘mismatch theory’, the capacity of the human genome to evolve defences against toxins has been outstripped by the pace of cultural change and technological development, such as purposeful fermentation of alcohol and more recently distillation of alcohol; purification and chemical manipulation of plant alkaloids; and the engineering of entirely novel psychoactive substances (NPS). The functions of the neurobiological substrates th...