Developments in neuroscience have raised the possibility that pharmaceuticals may be used to enhance memory, mood, and attention in people who do not have an illness or disorder, a practice known as “cognitive enhancement.” We describe historical experiences with two medicinal drugs for which similar enhancement claims were made, cocaine in the late 19th and early 20th centuries, and amphetamines in the mid 20th century. These drugs were initially introduced as medicinal agents in Europe and North America before becoming more (...) widely used for a variety of purposes, including what would nowadays be considered cognitive enhancement. Their trajectory of use conformed to the typical use cycle of psychotropic drugs. There was an initial steep rise in prescribing for medical use, followed by expanded nonmedical use that was fueled by enthusiasm for the drugs’ effects. As the number of regular users increased, problems related to use (such as addiction) became apparent, societal concern increased, and laws were passed banning nonmedical use and eventually, medical use. This historical experience draws attention to the adverse side effects of enhancement use that only become apparent with regular, wide-scale use of a drug. We highlight the similarities between the enthusiasms for cocaine and amphetamines and the current enthusiasms for using prescription stimulants for cognitive enhancement. We argue bioethicists should not encourage the cognitive enhancement use of drugs such as methylphenidate in the absence of evidence on the efficacy and safety of their use for cognitive enhancement purposes. (shrink)