Study procedures and sample

Definitions and measures

Statistical analysis

The statistical analyses were performed in R Statistical Language (version 4.3.2; R Core Team, 2023). Descriptive statistics were calculated, including frequencies, means, and standard deviations. To assess the significance of associations between categorical variables, such as reported use of CES by gender or age, the chi-square and Fisher’s exact tests for count data were employed. The significance level is established at p < 0.05. For group comparisons, Chi-square tests were used where group population (n) was higher than 5; otherwise, Fisher’s Exact Test was applied.

All our findings are discussed in the context of broader trends and existing literature, rather than being treated as definitive based on their statistical significance.

Participant description

A total of 288 students were included in the analysis for this study. The raw data are available in S2 File. Participants were selected based onhaving completed all demographic questions and indicating prior knowledge of cognitive enhancers. Although more participants initially began the survey, only those with complete data were retained in the final analysis. Participants ranged in age from 17 to 56 years, with an average of 23.1 years (SD = 3.5). For analytical purposes, respondents were divided into two age groups, those born before 2000 and those born in 2000 or later. The distribution of gender, level of current educational program (BSc, MSc, PhD), and country of origin (The Netherlands, other EU-countries, non-EU-countries) is presented in Table 1.

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Table 1. Participant characteristics (n = 288).

https://doi.org/10.1371/journal.pone.0332433.t001

Awareness of cognitive enhancers

When assessing participants’ prior knowledge and awareness of CES, we found that 51.7% of the study population reported having heard of CES (Table 2). A statistically significant difference was observed based on the particpants’ origin (p = 0.001). Specifically, 20.5% of Dutch students and 24.6% of students from other EU countries were familiar with CES, compared to a notably higher percentage among students originating from non-EU countries (52.1%). No significant differences were found across gender, age groups, or education level.

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Table 2. Awareness of cognitive-enhancing supplements (CES).

https://doi.org/10.1371/journal.pone.0332433.t002

Respondents who indicated that they had heard of CES or were unsure about their awareness, were presented with a multiple-response question to identify the sources through which they had obtained the information. The most frequently reported sources were family and friends (29.4%), the internet (26.6%), and social media (25.2%). These findings are consistent with a previous study conducted among university students in the United Arab Emirates [6], and align with results from studies in Switzerland and New Zealand, which similarly found that friends and social network were primary sources of information regarding CES [10]. Additional reported sources include pharmacies, medical books, commercials on TV, news, documentaries, TV shows, and podcasts.

When asked whether they had ever considered using CES themselves, 28.9% of the participants responded affirmatively. Among students aged 24 and older, 40.5% reported having considered using CES – significantly higher than the 21.1% reported by students younger than 24 (p = 0.005). To our knowledge, this age-related difference has not been reported before. It could be influenced by the fact that older students simply had more years of life to consider CES use.

A significant difference was also observed by country of origin: only 22.3% of Dutch students had considered using CES, compared to 48.4% of students from other EU countries and 47.8% from non-EU countries (p = 0.002). No significant differences were found based on gender (p = 0.983).

Overall, 36.6% of the participants consider it is taboo to use CES. This perception was significantly more prevalent among PhD students (72.2%) compared to BSc (30.4%) and MSc students (34.6%) (p = 0.003). The perception of CES as taboo is consistent with findings by Sharif et al.‘s (2021), who identified societal stigma and cultural expectations as key factors influencing CES use. Both studies suggest that the availability of CES and the influence of social interactions affect students’ use of these substances. Many students learn about CES through their social circles, family, and friends, as well as online sources like the internet and social media. This indicates that social relationships and access to information play a significant role in shaping students’ attitudes and behaviors regarding CES use, emphasizing the important role of peer networks and digital information in shaping perceptions.

In addition, a significantly larger proportion of Dutch students (41.5%) viewed CES use as taboo, compared to students from other EU countries (22.6%) and non-EU countries (21.7%) (p = 0.042). This suggests that cultural norms and societal attitudes in the Netherlands may contribute to this perception, which could, in turn, explain the lower rates of CES consideration among Dutch students.

Use rates of cognitive enhancers

Of the participants, 33 students (11.5%) reported having ever used CES (Table 3). No statistically significant differences in CES use were found based on gender (p = 0.154), age group (p = 0.122), education level (p = 0.513), or country of origin (p = 0.195). Given the significant differences observed in whether participants had heard about CES and whether they considered using the pills themselves, the lack of variation in actual usage rates across these demogaphic categories was somewhat unexpected. It is important to acknowledge that comparisons across studies are complicated by inconsistent definitions of CES. Some research focuses solely on pharmacological cognitive enhancers, while others include recreational substances like coffee, nicotine, or energy drinks. This inconsistency in definitions presents challenges for making accurate cross-study comparisons.

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Table 3. Usage of Cognitive-enhancing supplements (CES).

https://doi.org/10.1371/journal.pone.0332433.t003

In comparison to some other studies from other European countries, the use rate currently found is relatively low. For instance, a Portuguese study reported 31.1% usage of prescribed and nonprescribed drugs [11], a Greek study reported 21.5% usage [12], and a Swiss study reported 22% [13].

Almost half of the users (47.6%) have used CES only less than one month. The remained usedCES over longer periods, varying from 1–6 months (11.9%), 6–12 months (14.3%), 12–24 months (9.5%) to over two years (16.7%). Regarding access, 28.6% of CES users reported having a medical prescription. The majority of these prescriptions were for methylphenidate (9 out of 12), fllowed by dexamfetamin (3 out of 12). Notably, none of the PhD students in the sample reported having a medical prescription. Compared to a previous Dutch study, this percentage is very high, since Schelle et al [3] reported only 1.7% prescription use. Other European studies reported similarly low figures; 2.2% in France and Romania [14], 6.9% in Portugal [11], and 12% in Switzerland [13].

On the other hand, Maier et al [10] reported an increase in non-medical use of prescription stimulants (e.g., methylphenidate, dexamphetamine) in the Netherlands, from 8.2% in 2015 to 13.5% in 2017. If this upward trend has continued linearly, a 28.6% usage rate by 2024 may be plausible. This potential increase highlights the importance of ongoing monitoring and more nuanced investigation into patterns of CES use, including distinctions between medically supervised and non-medical usage.

Among the participants without a prescription, the most frequently consumed substance was caffeine (n = 16), followed by other substances specified by participants (n = 11). Other commonly mentioned substances included cobalamin (vitamin B12, n = 9), amphetamine salt mixtures (n = 6), methylphenidate (n = 6), and modafinil (n = 5). Additional reported substances were guarana (n = 4), pyridoxine (vitamin B6, n = 3), and vinpocetine (n = 1). Furthermore, participants mentioned consuming Ashwagandha, bacopa, vitamin D, L-theanine, L-tyrosine, fish oil, and supplements containing Rhodiola rosea, thiamine, riboflavin, pyridoxine, folic acid, and cyanocobalamin. Other CES cited included ritalin, dexamphetamine, citicoline, and ginkgo. These results illustrate the wide variety of compounds being used, with caffeine emerging as the most frequently mentioned substance. Also regarding participants who do not have a prescription, acces to CES is mainly through a physical shop in the Netherlands (26.2%), an online shop (23.8%), via a friend (21.4%), and in a pharmacy (19.0%). Other studies report higher shares (up to half of the participants) for sourcing via a friend [6,10]. This discrepancy may be attributed to differences in scope; while those studies focused primarily on prescription stimulants, the present study includes a broader range of supplements.

Regarding the perceived effects of CES use, participants most frequently reported increased attention and a general sense of activation (Fig 1).Long-term memory and creativity are mentioned by the least number of students. Additional perceived benefits included enhanced ability to structure thoughts and tasks, reduced anxiety or stress about failing, and increased energy levels. Adverse effects that were mentioned are increased, e.g., heart rate, headaches, anxiety, sleeping problems, tremors, overstimulation, weight loss, increased blood pressure. Ram et al. [15] found that the most frequently cited negative outcomes of CES use were dependence and poorer physical health, with unwanted adverse effects ranking fourth in their study. Although dependence was not explicitly reported as a side effect in our study, the presence of symptoms such as anxiety and sleep issues may indicate a potential link to dependency on CES.

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Fig 1. The answers to the question “What kind of pharmacological effects have you noticed during the use of cognitive-enhancing supplements (CES)?”.

https://doi.org/10.1371/journal.pone.0332433.g001

Safety and legitimacy of CES use

Beyond price, factors such as safety and authenticity of the CES could play a role in deciding whether or not to buy and use them. To explore this, participants were asked to score a number of these aspects on a 7-point scale. Results are presented in Table 4. Participants (n = 266) found it important to know whether CES are safe before use (average score of 1.4 and variance was low). However, when being asked whether they felt they had sufficient information to judge whether CES are safe, they gave an average score of 5.4 with a large variance. Apparently, there is quite some difference in this perception. When asked whether they think CES are safe to use, participants gave an average score of 4.0 (SD = 1.2), indicating a moderate level of uncertainty. As visualized in Fig 2, respondents consider it important to know whether CES are safe to use (red line), yet reported limited knowledge (purple line). Meanwhile, their trust in safety (blue line) and authenticity (green line) of CES was moderate. This gap between the perceived importance of safety and the lack of knowledge and trust may be cause for concern, as it reflects uncertainty about the quality and reliability of substances under consideration.No statistically significant difference in perceptions of safety were found based on gender, education level, and origin, and also not between CES users and non users. This is in contrast to the findings of Nguyen et al. [8], which suggest that users tend to believe that drugs are safer than they are perceived by non-users. However, both user and non-user groups in our study utilized comparable information sources and demonstrated similar, relatively limited drug safety knowledge.

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Table 4. Safety and legitimacy of cognitive-enhancing supplements (CES) usage (n = 266).

https://doi.org/10.1371/journal.pone.0332433.t004

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Fig 2. The answers to the question “To what extent participants agree to…?”.

Responses were measured on a 5-point Likert scale ranging from ‘Strongly disagree’ to ‘Strongly agree’.

https://doi.org/10.1371/journal.pone.0332433.g002

There are many different sources of information on the safety of CES. When considering the trust participants have, they trust scientific research the most (score 1.9 ± 0.9) and social media the least (score 5.4 ± 1.2). Personal experience (score 4.0 ± 1.6), experience of peers (score 3.9 ± 1.5), and information from websites (score 3.8 ± 1.4) scored in the intermediate range. Additional sources of information mentioned by participants included psychiatrist and other health care professionals, product suppliers, influencers, product labels, advertisements, and governmental organisations (such as the National Institute for Public Health and the Environment (RIVM)). One person answered that medicins in the EU are tested so much, that he/she has much trust in them. Another person checked specific websites from, e.g., the Netherlands pharmacovigilance centre Lareb (www.lareb.nl) and the socalled “pharmacotherapeutisch Kompas” by the National Health Care Institute (https://www.farmacotherapeutischkompas.nl).

Given the growing market for CES, these supplements have become increasingly vulnerable to fraudulent activities, such as the illicit addition of pharmaceuticals into herbal supplements to boost their effects and thereby sales [16]. Therefore, the participants were asked whether they think CES are authentic. The average score is 4.2 on the 7-point scale (SD = 1.1), indicating moderate trust. There was a significant difference between participants who use CES and those who do not (p = 0.003); users reported higher trust in the authenticity of these substances. They did not believe that their views on authenticity or safety were extreme in any direction, which is to be expected and supports the consistency of their responses. This aligns with existing literature on authenticity, where perceptions of safety and authenticity often remain moderate rather than polarized.

Limitations of the study and recommendations for future research

Although the authors have tried their best in setting up a valuable study, there are also some limitations:

• The study relies on self-reported data, which may be subject to social desirability. Participants might underreport or overreport their use of CES due to stigma, legal concerns, or memory inaccuracies.
• The sample consists of students from a single university (Wageningen University & Research), which limits the generalizability of the findings to other student populations in the Netherlands or internationally. Cultural, institutional, and academic pressures may differ significantly across contexts. Future studies should include participants from multiple universities across different regions or countries.
• The recruitment strategy relied on voluntary participation through flyers posted in student areas. This method may have introduced self-selection bias, attracting individuals with a particular interest in or experience with cognitive enhancement. Additionally, the sample size may not have been sufficiently large to ensure adequate representation of the entire WUR student population. Thus, caution is warranted when generalizing the findings of this study.
• The cross-sectional nature of the study limits the ability to infer causality or understand changes over time. Longitudinal research would be necessary to assess how awareness, attitudes, or usage patterns evolve during students’ academic careers.
• The study includes a broad definition of cognitive enhancers, ranging from prescription stimulants to over-the-counter supplements and even caffeine. This may introduce inconsistencies when comparing results with studies that focus exclusively on pharmacological substances.
• While use duration is briefly reported, there is limited information about dosage, frequency, or context of use (e.g., during exams vs. regular use). This makes it difficult to assess the actual intensity and risk of CES use.
• Subgroups such as PhD students, users with medical prescriptions, or specific country-of-origin categories may have had small sample sizes, limiting the statistical power and reliability of subgroup comparisons.
  • Although participants rated aspects like safety and authenticity, their interpretations of these terms may vary. For example, some may equate “authentic” with legality, while others may interpret it as purity or manufacturer transparency. Qualitative studies or mixed-methods designs could explore how students assess the safety, authenticity, and ethical implications of CES use. Understanding decision-making processes may inform targeted interventions and health communication strategies.
  • The study does not account for confounding variables such as academic pressure, mental health status, or previous experiences with medication, which may influence CES use and attitudes. Further research should examine the role of academic pressure, stress, mental health conditions, and performance anxiety as potential drivers of CES use. Including validated psychological scales could yield deeper insights into these associations. Since our study found notable differences in perceptions of taboo and acceptability across cultural groups, future research should further explore how social norms, peer influence, and stigma shape students’ attitudes and behaviors regarding CES use.

Despite these limitations, the study provides valuable insights into the awareness, attitudes, and behaviors surrounding cognitive enhancer use in a university setting, and it highlights key areas for further research and policy attention. Next to the issues mentioned above, laboratory testing of CES products reported by users would provide critical insight into the authenticity and safety of these substances. This could help bridge the gap between perceived and actual risks, especially in unregulated markets.

Furthermore, our findings underscore the need for universities to enhance health education initiatives aimed at increasing awareness and promoting safer practices regarding CES use. By addressing the gaps in safety knowledge and reliance on unverified sources, universities can play a pivotal role in mitigating potential risks associated with the misuse of these substances.