Cognitive enhancement (CE) is the pharmaceutical augmentation of mental abilities (e.g., learning or memory) without medical necessity. This topic has recently attracted widespread attention in scientific and social circles. However, knowledge regarding the mechanisms that underlie the decision to use CE medication is limited. To analyze these decisions, we used data from two online surveys of randomly sampled university teachers (N = 1,406) and students (N = 3,486). Each respondent evaluated one randomly selected vignette with regard to a hypothetical CE drug. We experimentally varied the characteristics of the drugs among vignettes and distributed them among respondents. In addition, the respondent’s internalization of social norms with respect to CE drug use was measured. Our results revealed that students were more willing to enhance cognitive performance via drugs than university teachers, although the overall willingness was low. The probability of side effects and their strength reduced the willingness to use CE drugs among students and university teachers, whereas higher likelihoods and magnitudes of CE increased this propensity. In addition, the internalized norm against CE drug use influenced decision making: Higher internalization decreased the willingness to use such medications. Students’ internalized norms more strongly affected CE abstinence compared with those of university teachers. Furthermore, internalized norms negatively interacted with the instrumental incentives for taking CE medication. This internalization limited the influence of and deliberation on instrumental incentives. This study is the first to provide empirical evidence regarding the importance of social norms and their influence on rational decision making with regard to CE. We identified previously undiscovered decision-making patterns concerning CE. Thus, this study provides insight into the motivators and inhibitors of CE drug use. These findings have implications for contending with CE behavior by highlighting the magnitude of potential side effects and by informing the debate regarding the ethics of CE use.