Pharmacological cognitive enhancers (PCEs) are used to improve cognitive functions, such as attention, learning, memory and planning in patients with impairments in cognition resulting from traumatic brain injury (TBI) or from neuropsychiatric disorders such as Alzheimer's disease (AD), mild cognitive impairment, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Moreover, PCEs have been shown to improve cognition in healthy volunteers with no psychiatric disorders. This article describes the rationale behind the need for their use in neuropsychiatric patients and illustrates how PCEs can ameliorate cognitive impairments, improve quality of life and wellbeing, and therefore reduce the economic burden associated with these disorders. We also describe evidence that PCEs are being used as cognitive enhancers by healthy people. Crucially, as the lifestyle use of these drugs becomes very popular in the healthy population, a final aim is to present an overview of the current and future neuroethical considerations of enhancing the healthy brain. As information regarding their actual use, benefits and harms in various healthy populations is currently lacking, we propose research that aims to obtain relevant empirical data, monitor the short- and long-term effectiveness and side-effects, and initiate accurate surveys to determine current patterns and quantity of usage of PCE drugs by healthy people. Furthermore, in order to instigate a dialogue between neuroethics and neuropsychopharmacology, we urge scientists to explore and communicate the social and ethical implications of their research to the public. Finally, we discuss and highlight other means of enhancing cognition in both patients and healthy adults, including education and physical exercise.

The author has declared no conflicts of interest for this article.

Modafinil is a drug licensed for the treatment of narcolepsy and sleep apnea. Recently, modafinil has been reported to be used as a pharmacological cognitive enhancer by healthy individuals with no psychiatric disorders. This paper reports on a study that investigated the effects of modafinil on divergent and convergent thinking tasks of creativity. Sixty-four healthy male (n = 31) and female (n = 33) volunteers participated in a randomized double-blind placebo-controlled parallel group design study. For the convergent thinking tasks, modafinil had no significant main effect on the Group Embedded Figures Task and the Remote Associates Task (RAT). However, a median split analysis showed that modafinil participants low in creativity personality trait had significantly higher RAT scores (Mean [M] = 6.85, SD = 3.39; 95% confidence interval [95% CI]: 5.53-8.2) than those high in creativity personality trait (M = 4.27, SD = 3.0; 95% CI: 2.4-6.0). For the divergent thinking tasks, relative to placebo (M = 1.195, SD = 0.28; 95% CI: 1.0-1.3), modafinil (M = 0.77, SD = 0.37; 95% CI: 0.63-0.92) significantly reduced the performance of flexibility scores and marginally reduced the elaboration scores as measured by the Abbreviated Torrance Test for Adults (ATTA). Overall, participants on modafinil (M = 6.3, SD = 2.6; 95% CI: 5.3-7.4) had significantly lower ATTA scores relative to participants on placebo (M = 9.5, SD = 2.3; 95% CI: 8.6-10.4). These results indicate that modafinil might reduce divergent thinking of creativity in healthy individuals. They suggest that, rather than being a more general cognitive enhancer, modafinil might have negative and subtle effects on creativity. However, the results are from a small-scale trial, which tested a small number of participants. Therefore, the results need to be interpreted with caution. A replication with a large sample of participants is recommended.

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BackgroundModafinil is a medication licensed for the treatment of narcolepsy. However, it has been reported that healthy individuals without wakefulness disorders are using modafinil off-label to enhance cognitive functioning. Although some studies have reported that modafinil improves cognitive task performance in healthy volunteers, numerous other studies have failed to detect cognitive enhancing effects of modafinil on several well-established neuropsychological tasks. Interestingly, several clinical and preclinical studies have found that improved cognitive task performance by modafinil is accompanied by slower response times. This observation raises the question as to whether this slowing of response time in healthy volunteers is a necessary and sufficient condition for cognitive enhancement with modafinil. The aim of the current experiment was to explore this question by investigating the effects of modafinil on the Hayling Sentence Completion Test (HSCT).MethodologySixty-four healthy volunteers received either a single dose (200 mg) of modafinil (n = 32) or placebo (n = 32) in a randomized, double-blind, placebo-controlled, parallel group study in which the principal outcome measures were response latencies on the response initiation and response inhibition sections of the HSCT.Principal FindingsParticipants dosed with modafinil had significantly longer mean response latencies on the HSCT for both the response initiation and response inhibition compared to participants dosed with placebo. However, participants in both groups made a similar number of errors on each of these measures, indicating that modafinil did not enhance the accuracy of performance of the task relative to placebo.ConclusionsThis study demonstrated that administration of single 200 mg doses of modafinil to healthy individuals increased the latency of responses in the performance of the HSCT, a task that is highly sensitive to prefrontal executive function, without enhancing accuracy of performance. This finding may provide important clues to defining the limitations of modafinil as a putative cognitive enhancer.Trial RegistrationClinicalTrials.gov NCT02051153

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