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. 2025 Jun 16;87(8):4975–4981. doi: 10.1097/MS9.0000000000003442

Exploring Cognitive Enhancers: from neurotherapeutics to ethical and regulatory challenges: a mini review

Abdulbasit Opeyemi Muili a, Adibi Victor Temilola b, Oyekunle Olufunmike Itunu b, Olanipekun Abdulazeez Olajide b, Conteh Deborah Ngozi b, Piel Panther Kuol c,*
PMCID: PMC12333774  PMID: 40787538

Abstract

This manuscript provides an outlook on using cognitive enhancers and their ethical implications. Cognitive enhancers, including prescription medications like modafinil and methylphenidate, over-the-counter supplements such as ginseng and caffeine, and novel nootropic agents like gene therapy and stem cell interventions, improve cognitive functions such as memory, focus, and learning. While they have shown efficacy in treating neurodegenerative disorders like Alzheimer’s disease and attention-deficit/hyperactivity disorder (ADHD), their growing use by healthy individuals raises ethical concerns. This paper addresses the benefits of cognitive enhancers, such as improved academic and professional performance, and the associated risks, including addiction, dependence, and long-term health consequences. It also delves into social and ethical issues, including disparities in access, fairness, coercion in competitive environments, and distinguishing between genuine and substance-enhanced achievements. Additionally, the paper examines current regulations and proposes stronger legal frameworks to address the increasing use of cognitive enhancers. In conclusion, while cognitive enhancers have potential therapeutic benefits, a balanced approach is needed to regulate their use and ensure they are not misused to gain unfair advantages, particularly in non-medical settings.

Keywords: cognitive, ethical, nootropic

HIGHLIGHTS

  • Cognitive enhancers, including prescription medications like modafinil and methylphenidate, over-the-counter supplements such as ginseng and caffeine, and novel nootropic agents like gene therapy and stem cell interventions, are used to improve cognitive functions such as memory, focus, and learning

  • cognitive enhancers have potential therapeutic benefits, a balanced approach is needed to regulate their use and ensure they are not misused to gain unfair advantages, particularly in non-medical settings

Introduction

From the beginning, individuals with high cognitive abilities have been able to establish themselves in their immediate environment or the society at large. People with higher cognitive skills are more efficient and productive, which is of great value in the society we currently find ourselves in. Therefore, individuals who find themselves on the other end of the spectrum due to various disorders and health problems, feel the urge to improve their usefulness to themselves and society, hence the need for cognitive enhancers[1]. Moreover, it is also no surprise, that people who are considered normal, i.e. without any form of medical disorder have also been found using cognitive enhancers to improve their ability to focus on their everyday activities[2]. However, the use of these cognitive enhancers by healthy individuals is of great concern due to the lack of clinical evidence regarding their efficacy, safety, and social consequences, especially in long-term use[3,4]. Therefore, this shows the need for studies in these areas to assess the current state, safety, and social consequences to provide solutions to tackle emerging issues in this area.

Background information

The use of cognitive enhancers is an ancient practice. Major advances in the modern pharmacology of cognitive enhancers occurred in the 1960s, including the work of the Romanian psychologist and chemist Corneliu Giurgea who synthesized piracetam and referred to compounds that enhance learning and memory as nootropics.

Currently, most drugs that have been approved by the appropriate drug agencies are geared towards improving the cognition of those with neurodegenerative disorders such as Alzheimer’s disease, and attention-deficit/hyperactivity disorders (ADHD), and these drugs have been shown to have modest efficacies.

Types of cognitive enhancers

Cognitive enhancers include prescription medication, over-the-counter supplements, and nootropic agents.

Prescription medication

Prescription medications are medications prescribed by health professionals to manage a disease or condition. Conditions like Alzheimer’s disease and ADHD are mostly treated using cognitive enhancers. These include Deanol, meclofenoxate, piracetam, modafinil, Methylphenidate, and Amphetamines[5-13].

Over-the-counter supplements

Supplements are bought over the counter mostly from a pharmacy or a grocery store. Supplements bought can be prescribed by a medical professional or for personal use. Major over-the-counter supplements include ginseng, ginkgo, Ashwagandha, and caffeine[14-17].

Novel nootropic agents

These are genomes and stem cells. Various trials are underway using gene therapy and stem cell interventions to replace dead neurons in neurodegenerative diseases. They have also helped in post-disease recovery from various conditions like Parkinson’s disease, traumatic brain injury, and stroke. Their working principle is their neuroplastic effects which help in rewiring and repairing damaged brain tissues and neurons. Various clinical trials have been conducted for Parkinson’s disease and traumatic brain injury, while therapy for stroke and other disorders is proven in animal models[18].

Current usage trend

For the sake of simplicity, the use of cognitive enhancers can be divided into two broad categories which are the use among the normal population and the use of nootropics among the population with a certain illness most of which are neurodegenerative diseases.

Among the normal population

Nootropics have been termed as smart drugs among these groups of people due to their ability to improve memory and cognitive function. Its wide popularity is due to its easy procurement of these drugs as they are plant-based. Additionally, technological advancements through the emergence of e-marketing have made them purchasable online, which has made them increasingly popular among students especially those in tertiary institutions[3,19]. Additionally, people who work in various sectors have also been known to use cognitive enhancers to be more efficient and to improve their productivity at their place of work.

Among the diseased population

Nootropics are used in acute or subacute conditions for treating memory, consciousness, and learning disorders. They are recommended for incipient brain damage, which manifests in memory loss, mental retardation, and qualitative changes in consciousness. Other indications may include chronic disorders of cognitive functions such as mental retardation or memory impairment. Nootropics are given relatively often in these cases, but their benefit, especially in more severe dementia, is questionable. They seem to be more effective in patients with mild cognitive disorders or the so-called benign senescent forgetting when there is only a slowing down of brain function without the development of dementia. Nootropics are sometimes used for attention and memory disorders due to fatigue and exhaustion. They are also used by children with minimal brain dysfunction syndrome and patients with encephalopathy, and their effect on myalgic encephalomyelitis (chronic fatigue syndrome) has also been tested. As cognitive enhancers, nootropics are administered to patients who have Alzheimer’s disease, schizophrenia, hyperkinetic disorder, or senile dementia.

Diagnosis of cognitive impairment

The diagnosis of cognitive impairment involves the evaluation of different cognitive domains including memory, thought, and perception. During diagnosis, it is important to note the difference between cognitive impairment and dementia as cognitive impairment though affecting various cognitive functions may not affect the quality of life (QoL) or daily functioning of the affected patient, whereas dementia is more progressive and severe, interfering with daily functioning and significantly affecting the QoL of the affected patient.

The diagnosis of cognitive impairment can be through neuropsychological testing, daily living and functional assessment testing, biomarker assessments, and radiologic examination with Neuropsychological testing and biomarker assessments being the most recommended tests for the diagnosis of cognitive impairment[20].

Neuropsychological testing

neuropsychological testing involves various examinations such as the Modified Mini-Mental State examination (MMSE), the Rowland Universal Dementia Assessment Scale (RUDAS), the Montreal Cognitive Assessment (MoCA), Toronto Cognitive Assessment (TorCA), National Institute for Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN), and Free and Cued selective Reminding test (FCSRT)[20-25]. These examinations test for general intellect, reading comprehension, attention, learning and memory, and reasoning among others[26]. Since these tests are standardized, the results of these tests can be compared with those of other people which can help the health professional in charge to draw conclusions and suggest possible recommendations and interventions to address any noted cognitive impairment[26].

Biomarkers

Moving beyond neuropsychological testing, cerebrospinal fluid biomarkers such as CSF tau protein and CSF β-amyloid 42 have emerged as the most useful biomarkers in testing for cognitive impairment[27]. They are particularly important since they can be used to detect pathological changes associated with neurodegenerative diseases and can differentiate cognitive impairment from neurodegenerative diseases like dementia.

Physical examination

Similar to neuropsychological testing, physical examination also involves the use of various tests in diagnosing cognitive impairment. Tests such as dual gait test, olfactory function test, and hearing test[21]. These tests are important in the prediction of cognitive impairment progression to dementia.

Radiological examination

Additionally, radiological examinations are also important as they utilize Neuroimaging modalities like Computed tomography (CT), Positron Emission Tomography, and Magnetic Resonance Imagery (CT)[26,28,29]. These scans can identify underlying pathological conditions that may progressively lead to cognitive impairment, such as stroke, Huntington’s disease, and Parkinson’s disease[30,31].

Benefits and risk

Potential benefits of cognitive enhancers

Many advantages have been recognized to come with cognitive enhancers, such as nootropic agents and pharmacological stimulants. Drugs such as meclofenoxate, amphetamines, dihydroergotamine, modafinil, and methylphenidate that are prescribed to treat attention deficit hyperactivity disorder, Alzheimer’s disease, and other related cognitive disorders have been effective in enhancing cognitive function[6,9-11,32].

Likewise, improvement in the academic, and professional achievement or performance of individuals has been associated with the use of agents such as Ritalin, Deanol, meclofenoxate, and Methylphenidate since the use of these agents helps to in raising the brain’s acetylcholine level. This increases an individual’s working memory, and attention thereby leading to greater learning outcomes and productivity in terms of effective completion of work-related tasks[33]. Other studies have also found that the use of these agents can also result in improved work habits and an overall improvement in job performance[34]. In addition, meclofenoxate is used to lessen the general slowing in speech, thinking, and mental activity brought on by CNS intoxication and injury. It also enhances the status of qualitatively altered consciousness and has an anti-hypoxic effect.

Equally, Omega-3 fatty acid is an example of a naturally occurring nootropic agent and has been shown to improve mental and cognitive deficits in affected individuals. A close nootropic agent similar to Omega-3 fatty acid is Ginkgo biloba which has almost the same effect. Treatment with Ginkgo Biloba extract indicated significant improvement in working memory and information processing speed. They have been widely prescribed to treat cerebral dysfunction and neurological disorders like Alzheimer’s disease[15]. Apart from helping in the therapeutic management of cognition-affecting diseases like Alzheimer’s disease, these agents may also help elderly people retain their memories and slow down the onset of memory loss and cognitive impairment[35,36].

Prevention of oxidative stress has been associated with the use of certain agents like ginseng and ashwagandha. Ginseng has been shown to have the ability to reduce the level of oxidants in the central nervous system and reduce the level of oxidative damage within the central nervous system[14]. Similarly, ashwagandha supplements have been linked to an increased content of hemoglobin, platelets, and red as well as white blood cells. An increase in red blood cells increases the blood’s ability to transport oxygen to the peripheral system, ensuring greater maximum aerobic capacity[16].

Moreover, Caffeine, which is the world’s most popular drug has the potential to improve cognition. According to experimental evidence, coffee may have cholinergic effects and increase central noradrenaline turnover in low arousal levels. However, according to new research, caffeine only improves cognition in those who are addicted to it while they are going through withdrawal, such as after 7-8 hours of sleep[17].

Associated risks of cognitive enhancers

There are serious harms that are associated with the use of these cognition-improving agents. Pharmacological stimulants have been found to have side effects on users, such as increased heart rate, increased or elevated blood pressure, anxiety, and sleep disturbances[37]. Excessive use of these drugs either in terms of dosage or duration of use leads to the development of tolerance and then subsequent dependence, which likely results in addiction and withdrawal symptoms[38]. Although it is unclear what future effects these stimulants and naturally occurring nootropic agents will have, there are still worries about how the use of these agents may affect brain health and cognitive development in young adults and adolescents whose brains are still growing[39].

Social and ethical implications that arise from the use of these agents are also quite important. In a competitive setting, the use of cognitive enhancers may lead to fairness problems because individuals who have access to and use these agents may be seen to have an unfair edge or advantage causing undue aggravation of already-existing disparities[40]. Also, compulsion which might arise from peer pressure on these agents can force individuals to use these drugs even in cases when they are not necessary[41]. Another ethical consideration is informed consent. Ignorant users of these agents may make potentially life-changing decisions regarding their health if they are unaware of the hazards and long-term effects of cognitive enhancers[42]. The ethical terrain is further complicated by the possibility of prescription pharmaceutical abuse and misuse for recreational purposes[43].

Ethical implications

The introduction of cognitive enhancers has opened up new avenues for human cognitive performance while also generating serious ethical concerns. These substances, which range from prescription medications like modafinil and methylphenidate to over-the-counter supplements, claim to improve various elements of cognitive function such as memory, focus, and mental stamina[44]. However, its growing use in academic, professional, and social settings has provoked controversy among ethicists, healthcare professionals, legislators, and the general public[45]. The ethical implications of cognitive enhancers go far beyond individual health problems, addressing fundamental themes such as fairness, authenticity, human identity, and societal values[41]. This exploration into the ethical implications of the use of cognitive enhancers is critical not just for informing current policy and personal choices, but also for shaping our collective approach to human cognitive potential in an era of rapid technological growth.

Equity and access

Disparities in access to cognitive enhancers raise substantial ethical considerations in the field of mental health. Although there have been proven benefits to these substances as earlier discussed, they are not equally distributed among individuals in society[41] and these disparities can present in any of the following ways:

Socioeconomic disparities

People with higher earnings and better access to healthcare are more likely to obtain cognitive enhancers, whether through legal prescriptions or illicit routes. This provides an unfair advantage in academic and professional settings and may exacerbate already existing socioeconomic disparities[44].

Geographic disparities

People’s access to these substances may also differ based on their geographic location. Individuals in urban and developed areas may have better access than those in rural and developing settings[46].

Healthcare system biases

Variations in healthcare systems and insurance coverage can cause unequal access to cognitive enhancers. Healthcare system biases: Some individuals may obtain these medications as treatment for documented and diagnosed disorders, while others with the same or similar issues may be denied access owing to a lack of diagnosis or insurance coverage[45].

The effects of these disparities on access to cognitive enhancers are cyclical. Those with higher socioeconomic positions who most likely also reside in better geographical locations have better access to cognitive enhancers, which may improve cognitive performance and, as a result, academic or professional achievement. This achievement supports their greater socioeconomic standing, resulting in a self-sustaining circle of advantage[41].

Pressure and coercion

The availability of cognitive enhancers creates new levels of pressure in a variety of situations, particularly academic and professional where the environment is competitive. This potentially leads to coercion as an individual may feel compelled to use these substances to be at par with their peers or meet certain expectations[40]. In academic settings, for example, students may feel the need to take cognitive enhancers to keep up with increasingly competitive and demanding academic expectations. It has been found that this can be particularly acute in high-stakes educational environments such as medical or law schools[47].

Also worthy of note is professional settings where employees face demanding implicit or explicit expectations and may be compelled to improve their cognitive performance by taking substances. This can foster a culture in which cognitive development is viewed as important for career advancement[40].

Another ethical debate on the use of cognitive enhancers is in sporting competitions. It particularly raises concerns about fairness and what defines cheating[48]. Many individuals also face “peer pressure” which makes them use these cognitive enhancers although there are no personal indications for the use other than the need to keep up with “trends” and their peers[49].

All of these raise the issue of coercion as demanding environments may directly or indirectly impact the decisions of individuals to use or not to use cognitive enhancers[50].

Authenticity and integrity

The use of cognitive enhancers raises serious concerns regarding the veracity of accomplishments and the integrity of personal and academic endeavors. Cognitive enhancers jeopardize authenticity and integrity as they can potentially provide an unfair advantage to individuals who use them[51]. Cognitive enhancers can make it difficult to distinguish between an individual’s innate abilities and the impact of the substances to improve cognition which can potentially undermine genuine achievements[52]. In educational settings, the use of cognitive enhancers may be interpreted as cheating, jeopardizing the integrity of academic examinations and the educational process itself[53]. Consistent usage of cognitive enhancers may raise suspicions about one’s genuine identity. If an individual’s better cognitive function is dependent on these substances, there may be a mismatch between their enhanced and natural states, which could lead to identity crises or feelings of inauthenticity[51].

These ethical questions emphasize the nuanced effects of cognitive enhancers on mental health and society as a whole. They emphasize the importance of strict regulation, equal access, and ongoing ethical discussions as these technologies evolve and become more ubiquitous.

Diagnostic ambiguities and ethical challenges

The diagnosis of cognitive impairment is faced with false Subjective Cognitive Complaints from individuals who intentionally exaggerate or fabricate symptoms in an attempt to get a legal prescription for cognitive enhancers despite not having a cognitive deficit. This issue is often influenced by factors such as stress, anxiety, and depression which can be associated with pressure, coercion, or societal expectations for improved performance in academic and professional settings[54,55]. As a result, subjective cognitive complaints have been evaluated as not being consistent with objective cognitive impairment in studies, due to the rising incidence of diagnostic ambiguities and its association with cognitive enhancer use[56].

Furthermore, this inconsistency can be mostly evident in neuropsychological and physical tests where individuals can intentionally fail these tests and manipulate their performance to appear cognitively impaired, thereby misleading clinicians.

This misrepresentation has a major impact on Equity and access since unjust access to cognitive enhancers can lead to unfair advantages in academic and professional settings justifying the point buttressed in section 4.3 above. Moreover, the principle of informed consent in the patient-clinician relationship is indirectly undermined as a false diagnosis is being issued by the clinician due to inaccurate information from the patient.

Legal and regulatory perspectives

Current regulations

Current regulations on the use of cognitive enhancers vary widely and are mostly based on jurisdiction. In many countries, cognitive enhancers such as modafinil and methylphenidate are considered prescription medications, with legal access limited to certain illnesses such as narcolepsy and ADHD[52]. However, off-label applications for cognitive improvement remain unclear.

In the United States, regulation for the use of cognitive enhancers is provided for by the Controlled Substances Act, which classifies them based on their potential for misuse and acknowledged medicinal usage[53]. In Europe, similar regulations exist as provided by the European Medicines Agency (EMA), authorizing use only for medical illnesses and not in healthy individuals for cognitive improvement[57].

It is important to mention that in countries like Nigeria, laws that expressly address the use of cognitive enhancers do not exist and their use is guided mainly by broader pharmaceutical and drug control laws.

Proposals for change

Given the ethical issues and potential hazards involved with cognitive enhancers, the following regulatory modifications are recommended:

  1. Reclassifying certain cognitive enhancers would make them more accessible, as restricted availability may be preferable to unregulated black-market distribution.

  2. Adopting stricter monitoring systems to track the distribution and usage of cognitive enhancers, would prevent misuse as well as allow for proper documentation of data on long-term effects of usage.

  3. More funding and support for long-term effects research on cognitive enhancers, would help to inform policy decisions and to assure public safety.

  4. The general public should be educated on the potential benefits and risks associated with the use of these substances.

  5. International cooperation is also needed to develop regulations on the use of cognitive enhancers as it is becoming a global issue.

Strength and limitation

This section provides an overview of the strengths and limitations of this current review to provide a comprehensive understanding of its scope, reliability and identify potential areas for improvement.

This study has several strengths, such as being the pioneer study providing an outlook on ethical considerations regarding the use of cognitive enhancers. Additionally, the moderate number of studies retrieved from the literature search ensured a comprehensive analysis, allowing an in-depth exploration of the topic. Moreover, the inclusion of non-English studies prevented language bias, ensuring that diverse perspectives and findings from different cultures were considered.

However, despite the strengths of the study, there is one limitation that should be considered. The primary limitation is the lack of a wide range of evidence-based results. This problem can be associated with the quantity and relevance of the included studies, resulting in temporal bias that can affect the reliability of the study findings.

Conclusion

In conclusion, cognitive enhancers have shown promise increasingly in addressing cognitive impairment, especially in Alzheimer’s disease patients and other diseases such as attention deficit hyperactivity disorder (ADHD). The rising popularity of these drugs among healthy people raises major ethical, social, and health risks even if they have been shown to improve productivity, memory, and other aspects of cognition. Access gaps make it more difficult to employ these enhancers equally, especially across different financial and demographical groups. Also, it is critical to know the risks linked to addiction and dependence as well as the long-term effects these actions have, especially among adolescents. To fully grasp the potential of cognition-enhancing agents and deal with the increasing ethical and societal issues as they arise, a careful approach is required. Clear limitations ought to make sure that these agents are available to those with genuine medical needs while preventing their improper use by well-meaning individuals looking to obtain a disproportionate advantage over others. Promoting equal opportunity and raising public awareness of the benefits and drawbacks of these agents are essential. Society may effectively regulate the increasing use of cognitive stimulants while guaranteeing that technological advancements are in line with ethical standards and for the benefit of the general public by endorsing legislation and providing funds for long-term research.

Footnotes

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Published online 16 June 2025

Contributor Information

Abdulbasit Opeyemi Muili, Email: muiliabdulbasit@gmail.com.

Adibi Victor Temilola, Email: adibivictor07@gmail.com.

Oyekunle Olufunmike Itunu, Email: olufunmikeitunu0307@gmail.com.

Olanipekun Abdulazeez Olajide, Email: olanipekunabdulazeez@gmail.com.

Conteh Deborah Ngozi, Email: debbieconteh@gmail.com.

Piel Panther Kuol, Email: jokpiel003@gmail.com.

Ethical approval

Not required.

Consent

Not required.

Sources of funding

Authors did not receive any funding for this review.

Author contributions

Conceptualization: A.O.M.; writing – original draft: A.O.M., P.P.K., A.V.T., O.O.I., O.A.O., C.D.N. Writing – review & editing: A.O.M.; P.P.K.

Conflicts of interest disclosure

No conflict of interest declared.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Muili Abdulbasit Opeyemi.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statement

Not applicable.

Assistance with the study

None.

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