Introduction: Cognitive enhancers (CEs), also known as “smart drugs”, “study aids” or “nootropics” are a cause of concern. Recent research studies investigated the use of CEs being taken as study aids by university students. This manuscript provides an overview of popular CEs, focusing on a range of drugs/substances (e.g., prescription CEs including amphetamine salt mixtures, methylphenidate, modafinil and piracetam; and non-prescription CEs including caffeine, cobalamin (vitamin B12), guarana, pyridoxine (vitamin B6) and vinpocetine) that have emerged as being misused. The diverted non-prescription use of these molecules and the related potential for dependence and/or addiction is being reported. It has been demonstrated that healthy students (i.e., those without any diagnosed mental disorders) are increasingly using drugs such as methylphenidate, a mixture of dextroamphetamine/amphetamine, and modafinil, for the purpose of increasing their alertness, concentration or memory. Aim: To investigate the level of knowledge, perception and impact of the use of a range of CEs within Higher Education Institutions. Methodology: A systematic review was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Whilst 1400 studies were identified within this study through a variety of electronic databases (e.g., 520 through PubMed, 490 through Science Direct and 390 through Scopus), 48 papers were deemed relevant and were included in this review. Results: The most popular molecules identified here included the stimulant CEs, e.g., methylphenidate, modafinil, amphetamine salt mixtures and caffeine-related compounds; stimulant CEs’ intake was more prevalent among males than females; drugs were largely obtained from friends and family, as well as via the Internet. It is therefore suggested that CEs are increasingly being used among healthy individuals, mainly students without any diagnosed cognitive disorders, to increase their alertness, concentration, or memory, in the belief that these CEs will improve their performance during examinations or when studying. The impact of stimulant CEs may include tolerance, dependence and/or somatic (e.g., cardiovascular; neurological) complications. Discussion: The availability of CEs for non-medical indications in different countries is influenced by a range of factors including legal, social and ethical factors. Considering the risk factors and motivations that encourage university students to use CE drugs, it is essential to raise awareness about CE-related harms, counteract myths regarding “safe” CE use and address cognitive enhancement in an early stage during education as a preventative public health measure.

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Smart drugs' (also known as 'nootropics ' and 'cognitive enhancers' [CEs]) are being used by healthy subjects (i.e. students and workers) typically to improve memory, attention, learning, executive functions and vigilance, hence the reference to a 'pharmaceutical cognitive doping behaviour'. Whilst the efficacy of known CEs in individuals with memory or learning deficits is well known, their effect on non-impaired brains is still to be fully assessed. This paper aims to provide an overview on the prevalence of use; putative neuroenhancement benefits and possible harms relating to the intake of the most popular CEs (e.g. amphetamine-type stimulants, methylphenidate, donepezil, selegiline, modafinil piracetam, benzodiazepine inverse agonists, and unifiram analogues) in healthy individuals. CEs are generally perceived by the users as effective, with related enthusiastic anecdotal reports. However, their efficacy in healthy individuals is uncertain and any reported improvement temporary. Conversely, since most CEs are stimulants, the related modulation of central noradrenaline, glutamate, and dopamine levels may lead to cardiovascular, neurological and psychopathological complications. Furthermore, CEs' use can be associated with paradoxical short-and long-term cognitive decline; decreased potential for plastic learning; and addictive behaviour. Finally, the non-medical use of any potent psychotropic raises serious ethical and legal issues, with nootropics having the potential to become a major public health concern. Further studies investigating CE-associated social, psychological, and biological outcomes are urgently needed to allow firm conclusions to be drawn on the appropriateness of CE use in healthy individuals. Key points• Cognitive enhancers (CEs) are extensively and increasingly being used by healthy active subjects, with student use having been reported in the range of 1.3-33% across studies, with variations depending on country and definition of cognitive doping. However, their efficacy on non-impaired brains is uncertain and any reported improvement is temporary. • Conversely, since most CEs are stimulants, the modulation of central neurotransmitter pathways could lead to severe complications and can be associated with paradoxical short-and long-term cognitive decline; decreased potential for plastic learning; and addictive behaviour. • Finally, non-medical use of CEs raises serious ethical and legal issues, and CEs have the potential to become a major public health concern

Background Cognitive enhancers (CE) are often used to improve memory, alertness and cognitive capacity. These products are commercially and pharmaceutically available. Due to high academic pressure, university students are at risk of CE misuse. However, data regarding this issue are limited, especially in the United Arab Emirates (UAE). Aims To assess the prevalence of CE intake; evaluate students’ knowledge of these substances; and identify student characteristics associated with CE usage. Method A cross sectional study based on a validated online survey that was distributed using university-licensed software (Qualtrics) as a direct web link via email and social media to all Medical, Pharmacy, Dentistry, Nursing and Engineering students enrolled in six UAE universities. Associations between student characteristics and CE use were investigated using the chi-squared test and multiple logistic regression. Reasons for CE use, temporal patterns of use, details regarding purchase and types of CE used were compared by gender. Results One quarter of students had used CEs. There was a clear difference between users and non-users in terms of gender (p<0.001). CE users were disproportionately represented by students from either UAE or other Arab countries (p<0.001), and by students of Medicine, followed by Pharmacy, Dentistry, and Engineering (p<0.001). CE use increased with year of study, reaching the highest level in the fourth year (p<0.001), which for most programmes is the final year. Modafinil was self-administered, especially in males, for concentration and alertness; B12 was typically taken by female students for academic performance and concentration; and high-dosage caffeine compounds were ingested to improve alertness levels. Use of the internet for both obtaining information and purchasing CEs was frequently reported. Multiple logistic regression analysis showed that gender, nationality, and year of study were associated with CE use among UAE university students. Conclusions Universities need to address the prevalence of CE use amongst their students by providing effective support programs.

The third author's name, which is currently presented as Sophia Sharif, should be presented as Safia Sharif.The original article has been corrected.