Neuroethical Issues in Cognitive Enhancement

Why are Smart Drugs Needed?

Cognitive-enhancing drugs, also known as smart drugs, are needed to treat cognitive disabilities and improve the quality of life for patients with neuropsychiatric disorders and brain injury. Cognitive-enhancing drugs are used in treating cognitive impairment in disorders such as Alzheimer’s disease (AD), schizophrenia and Attention Deficit Hyperactivity Disorder (ADHD). In neurodegenerative diseases, such as AD, cognitive-enhancing drugs are used to slow down or compensate for the decline in cognitive and behavioural functioning that characterizes such disorders. There are currently 700,000 people with dementia in the UK, most of whom have AD. Each year, 39,400 new cases are diagnosed in England and Wales, translating to a new case every 14 minutes. Current costs of long-term care for dementia in the UK are estimated at £4.6 billion, and with an increasing aging population, this estimate is expected to rise to £10.9 billion by the year 2031 (Knapp and Prince, 2007). Likewise, the number of people placed in institutions is expected to rise from 224,000 in 1998 to 365,000 in 2031. Cognitive-enhancing drugs are important in this context as it has been suggested that a treatment that would reduce severe cognitive impairment in older people by just 1% a year would cancel out all estimated increases in the long-term care costs due to the aging population in the UK (Knapp and Prince, 2007).

Cognitive enhancers may be beneficial not just in neurodegenerative disorders but also in neuropsychiatric disorders for which they are not yet routinely prescribed. For instance, though it is common knowledge that people with schizophrenia typically suffer from hallucinations and delusions, it is the long-term cognitive impairments that often impede everyday function and quality of life for many patients. Twenty four million people world wide suffer from schizophrenia (World Health Organization, 2008). In the USA, direct and indirect costs were estimated at over $60 billion in the year 2000 (Wu et al., 2005). It has been suggested that even small improvements in cognitive functions could help patients make the transition to independent living (Davidson and Keefe, 1995).

However, it is not only adults suffering from neuropsychiatric disorders that benefit from cognitive-enhancing drugs. ADHD affects 3 to 7% of all children worldwide, and is the most prevalent neuropsychiatric disorder of childhood (American Psychiatric Association, 2000). ADHD is a highly heritable and disabling condition characterized by core cognitive and behavioural symptoms of impulsivity, hyperactivity and/or inattention. It has important implications for education provision, long-term social outcomes and economic impact. For example, long-term studies indicate it is associated with poorer long-term outcomes, including increased educational dropout, job dismissal, criminal activities, substance abuse, other mental illness and increased accident rates (Barkley, 2006). The annual excess cost of ADHD in the USA in 2000 was estimated to be $42.5 billion (Pelham et al., 2007).

Whilst it is pharmacological cognitive enhancers (PCEs) that we will consider in this paper, there are numerous methods of boosting one’s brain power. Some additional methods under development are neuroprosthetics for cognition, and transcranial magnetic stimulation. Importantly, there are many others such as education, physical exercise and neurocognitive activation or cognitive training that are commonly being used (Beddington et al., 2008; Hilman et al., 2008; Willis et al., 2006).

Research on Cognitive Enhancers

Despite the fact that much research has been dedicated to the development and understanding of various cognitive enhancers, we still have limited knowledge as to how specific cognitive functions are modulated by neurotransmitters. For example, whilst we know that methylphenidate improves symptoms of ADHD and improves performance on objective behavioural tasks, such as spatial working memory and stop signal, we have yet to determine conclusively whether dopamine, noradrenaline or both neurotransmitters are required for these effects on cognition. Some of the most notable PCEs being explored to assist individuals with neurological or neuropsychiatric disorders with executive function and attention difficulties include methylphenidate, atomoxetine and modafinil (Stahl, 2008). Methylphenidate, also commonly known as Ritalin, increases the synaptic concentration of dopamine and noradrenaline by blocking their reuptake. Atomoxetine (Strattera) on the other hand, is a relatively selective noradrenaline reuptake inhibitor. In the case of modafinil (Provigil), despite considerable research its precise mechanism of action is unclear, although it has been found to exhibit a multitude of effects including potentiation of noradrenaline and, to a degree, dopamine neurotransmission (Volkow et al., 2009), elevation of extracellular glutamate, serotonin and histamine levels, and decreased extracellular GABA (Minzenberg and Carter, 2008). Recent evidence suggests that some of its cognitive effects may be modulated primarily by noradrenaline transporter inhibition (Minzenberg et al., 2008).

An effective method of testing the effects of cognitive enhancers on cognition is by using double-blind placebo-controlled studies where participants undergo a battery of objective cognitive tasks targeted at measuring various facets of cognition, including memory, attention and executive functions. For example, in the CANTAB Spatial Working Memory task (SWM), a number of coloured boxes are shown on the screen (Owen et al., 1990). The aim of this task is that, by touching the boxes and using a process of elimination, the subject should find one blue ‘token’ in each of a number of boxes. The number of boxes is gradually increased, until it is necessary to search a total of eight boxes. SWM is a test of the subject’s ability to retain spatial information and to manipulate remembered items in working memory. It is a self-ordered task, which also assesses heuristic strategy. This test is sensitive to frontal lobe and ‘executive’ dysfunction (Owen et al., 1990) and is impaired in childhood and adulthood ADHD (Kempton et al., 1999; McLean et al., 2004; Mehta et al., 2004).

It has been demonstrated that methylphenidate improves spatial working memory performance both in young volunteers with ADHD and in adult patients with ADHD, whereby patients make fewer task-related errors when on methylphenidate (Mehta et al., 2004; Turner et al., 2005). The neural substrates mediating SWM task performance have been examined using imaging techniques such as positron emission topography (PET) and indicate that the dorsolateral and mid-ventrolateral prefrontal cortex are particularly recruited (Owen et al., 1996). Studies using PET and contrasting [(11)C] raclopride binding, with the subject on versus off methylphenidate, have further indicated that methylphenidate influences dopaminergic function, particularly in the striatum (Wang et al., 1999). Methylphenidate has been found to improve both performance and efficiency in the spatial working memory neural network involving the dorsolateral prefrontal cortex and posterior parietal cortex in healthy volunteers (Mehta et al., 2000).

Similar studies using the double-blind, randomized placebo-controlled methodology have reported that additional drugs such as modafinil and atomoxetine can improve performance in some tasks of executive functioning. Thus, modafinil has been found to improve spatial planning and response inhibition in ADHD patients, as measured by a variant of the Tower of London task and the stop signal task, respectively (Turner et al., 2004). It has been further demonstrated that modafinil produced improvements in performance in a group of healthy volunteers on tests of spatial planning, response inhibition, visual recognition and short-term memory (Turner et al., 2003). Likewise, administration of an acute dose of atomoxetine has been found not only to improve response inhibition in ADHD patients (Chamberlain et al., 2007), but also in healthy adults (Chamberlain et al., 2006). Using functional Magnetic Resonance Imaging (fMRI), the brain mechanisms by which atomoxetine exerts its effects in healthy volunteers has been examined in a double-blind placebo-controlled study (Chamberlain et al., 2009). Atomoxetine led to increased activation in the right inferior frontal gyrus when participants attempted to inhibit their responses in the stop signal task. Inhibitory motor control has been shown previously to depend, at least in part, on the function of this brain region (Aron et al., 2003).

Such results demonstrate the potential of drugs to enhance certain domains of cognition. At the same time, psychopharmacological research entails the consideration of several complex factors (Morein-Zamir et al., 2008). These include neurotransmitter function at times following an inverted U-shaped curve, with deviations from optimal level in either direction impairing performance (e.g., Ramos and Arnsten, 2007; Tannock et al., 1995). Likewise, different neurotransmitter levels can be found across brain regions, suggesting a complex interplay between baseline levels and drug administration. While some cognitive functions may improve following drug administration, others may worsen, as they depend on different optimum neurotransmitter levels (Cools and Robbins, 2004). These and related findings strongly suggest that drug-induced neurotransmitter increases may improve functioning in some groups but have no effect or even impair performance in others, already at optimum. In accordance, it is not uncommon for PCEs to improve performance primarily or exclusively in individuals with greater impairment (Mehta et al., 2000). With increasing understanding of the brain’s neurochemistry, using imaging techniques and animal models, the complex roles of pre-existing baseline levels, drug dosage and individual differences are becoming more apparent (Morein-Zamir et al., 2008).

The Interest in Cognitive Enhancement

There is a clear trend in many western countries towards increasing prescriptions of methylphenidate (Farah, 2005). With the advent of psychiatric medications with greater tolerability and fewer side effects (though see Swanson et al., 2007), these trends are set to continue. However, it is not only those who suffer from neuropsychiatric and neurological disorders who are appearing to use PCEs. The use of stimulants, including methylphenidate and amphetamines, by students has been rising as well. Trends suggest that between 1993 and 2001 there was a clear increase in the life-time and 12-month prevalence rates of non-medical use of prescription drugs in college students (McCabe et al., 2007). In the USA, studies indicate that up to 16% of students on some college campuses use stimulants (Babcock and Byrne, 2000; McCabe et al., 2005), while 8% of university undergraduates report having illegally used prescription stimulants (Teter et al., 2005). Surveys on students indicate that most illicit use of prescription stimulants reported in the past year involve amphetamine-dextroamphetamine combination agents (e.g., Adderall), with higher use amongst Caucasians and Hispanics compared with African-Americans and Asians, and with considerable variations between colleges (Teter et al., 2006). The most commonly reported motives for use were to aid concentration, help study and increase alertness (Teter et al., 2006). There is also a trend for increasingly younger students to use such drugs, with one report indicating that 2.4% of eighth graders (13–14 years old) abused methylphenidate, as did 3.4% of tenth graders and 4.4% of twelfth graders (Johnston et al., 2006; see also McCabe et al., 2004). The trends are also not reserved solely for North America, as prescriptions rates in England of stimulants have been rising steadily from 220,000 in 1998 to 418,300 in 2004 (Niyadurupola, 2007; see also Turner and Sahakian, 2006). Though drugs such as modafinil are prescribed off-label in North America, they can be freely obtained without prescription via the internet from multiple websites in various countries. In fact, a recent survey identified 159 sites offering drugs for sale, only two of which were regulated, and 85% not requiring a physician’s prescription from the patient (Califano, 2008). Another cognitive domain of great interest is memory. Given the aging population in the UK and elsewhere, and the fact that the lifespan of individuals is being extended, it is highly likely that cognitive-enhancing drugs that can improve memory in healthy elderly people will prove to be in demand.

The popular media has reported extensively both on studies finding improved performance in healthy individuals and on the rising use of PCEs in healthy individuals. For example, the results of the study by Turner and colleagues (2003) on modafinil were reported in the media, including papers, magazines and radio. Papers ranging from The Guardian to The New Yorker and Nature, as well as the BBC, have discussed their potential for widespread use (Ghosh, 2007; Maher, 2008; Meikle, 2002; Talbot, 2009). Maintaining an optimum level of alertness, arousal and attention might be expected to prove valuable in a range of work and leisure activities. Indeed, the use of PCEs is not restricted to academia, and American sprinter Kelli White received a two-year ban in 2004 due to the use of modafinil when competing in the world championships and other US nationals.

These trends of growing use are likely set to increase as presently there are also novel cognitive enhancers under development, many of which are aimed at improving memory and learning. For example, ampakines, which work by enhancing the AMPA receptor’s response to glutamate, improve cognition in healthy aged volunteers (Lynch, 2004). Novel compounds such nicotinic alpha-7 receptor agonists are now in phase 2 of clinical trials in Alzheimer’s disease and schizophrenia (e.g., MEM 3454 Memory Pharmaceuticals/Roche; Mazurov et al., 2006).

The Neuroethics of Cognitive Enhancement

The study of cognitive-enhancing drugs, and their influence both on patients with neuropsychiatric and neurological disorders and healthy adults, raises numerous neuroethical issues. Neuroethics is defined as the study of the ethical, legal and social questions that arise when scientific findings about the brain are carried into medical practice, legal interpretations and health and social policy (Marcus, 2004). In response to the advances in cognitive neuroscience and neuropsychiatry and their increasing potential for broader application in the ‘real world’, and in part to the use of PCEs in healthy individuals, the Neuroethics Society (www.neuroethicssociety.org) was established (Nature Editorial, 2006). Neuroethics is a subfield within the broader domain of bioethics, which encompasses the ethical and moral implications of all biological and medical advances. Neuroethics was established to address the rapid developments within cognitive neuroscience and neuropsychiatry, and addresses findings relating specifically to the sciences of the mind, encompassing the central nervous system and the underlying brain mechanisms of human behaviour.

It is clear that research conducted by neuroscientists is now eliciting profound ethical implications: there are a whole range of ethical issues being raised due to neuroethical research from the use of PCEs in healthy individuals to the use of fMRI technology in military, civil and legal domains (Farah et al., 2004). We have advocated elsewhere that these ethical considerations in regard to societal issues should be part of training in neuroscience courses (Sahakian and Morein-Zamir, 2009). Neuroethics instruction to students is important because these future researchers should have some responsibility, as scientists and as members of society, as to the consequences of their research and how it may impact on society. We will now consider the ‘rights’ and ‘wrongs’ of cognitive enhancement in healthy people.

There are many potential positive outcomes for the use of cognitive enhancers in healthy adults. In addition to scientific and clinical advances, cognitive enhancement may lead to the removal of unfair disparity in society. Likewise, such drugs may lead to increased performance in both pleasurable and competitive activities. In an attempt to increase discussion on the topic and understand the subjective effects of healthy individuals taking modafinil for cognitive enhancement purposes, Sahakian and Morein-Zamir (2007) interviewed several scientists who have taken modafinil. The subjective effects ranged from moderate to ‘mild but very valuable to me’, and the academics interviewed reported varied effects on cognition including global effects on attention, working memory, word finding, improved sustained hard thinking and increases in mental energy. Better performance may in particular be valuable for individuals working in military roles, as shift workers or in positions that entail responsibility for the safety of many such as air traffic controllers. The Research and Development organization for the US Department of Defence (DARPA) has stated that

Similar cognitive enhancement effects may seem desirable also in others, such as surgeons. However, long-term studies by the pharmaceutical industry to ensure safety and efficacy in healthy people are still required. Part of ensuring the safety of the use of these drugs long-term would be to address their potential for substance abuse, as there is also the potential for abuse of certain PCEs, such as methylphenidate (Bright, 2008).

Indeed, the potential harms of cognitive enhancement in healthy individuals must not be overlooked. Namely, there could be long-term side effects or risks, which would be unacceptable given that this is not medical treatment. Patients with debilitating symptoms will often tolerate the side effects of drug treatment because improvements in symptoms outweigh the negative aspects, but this is not the case for cognitive enhancers in healthy individuals (Turner and Sahakian, 2006). Safety concerns are particularly pertinent in the developing brain. Administering drugs to children, who are more vulnerable, may elicit additional harms not apparent in adults (Swanson et al., 2007). Clinical monitoring in this group is even more vital than in adults given the necessary prevalent off-label use, at times the potential for abuse, and the lack of clinical trials in this population (Zito et al., 2008). Additional safety concerns include drug–drug interactions and the presence of contraindications, which may become even more challenging with the increasing availability of PCEs via the internet (Sahakian and Morein-Zamir, 2007).

Another concern is the possibility of people being coerced or even forced into taking cognitive enhancers. This may occur explicitly, for example requiring that workers be alert during a night shift; or it may take on more subtle forms, such as providing a competitive environment where incentives are offered for best performance (Farah et al., 2004). In accordance, surveys indicate that the majority of college students overestimate the prevalence of non-medical use of prescription stimulants, leading to misperceived norms which in turn may promote such behaviour (McCabe et al., 2008). This may result in an overworked 24/7 society where people are pressured into working ever longer hours to the detriment of their own and their family’s wellbeing. Concerns have also been raised regarding the possibility of greater inequality with the increased use of cognitive enhancers, if access is dependent on wealth (Chatterjee, 2004; Farah et al., 2004). This is true both between individuals (due to socioeconomic status and financial means), and between nations, as has occurred in the past with some medical advances (Ashcroft, 2005). Alternatively, given the likelihood that some PCEs may be affordable, costing about the same as a cup of coffee (Lennard, 2009), they could be adopted in disadvantaged populations, as was the case of mobile phones. Nevertheless, it is uncertain how the allocation and funding of various cognitive enhancers should be controlled and what the decision-making process should be.

This leads to another concern regarding how healthy individuals may obtain PCEs, ensuring both fair and safe access. Presently, in the USA and the UK, drugs such as modafinil, atomoxetine and methylphenidate require a doctor’s prescription as these drugs are regulated for administration in psychiatric or medical conditions (Niyadurupola, 2007). Off-label prescriptions, or the prescription of a medication for a condition not described in the approved labelling, are very common and legal (Radley et al., 2006), and there is very limited regulation of off-label drugs with prescriptions, relying largely on the physician’s discretion (Hampton, 2007). Hence modafinil, for instance, can be prescribed for people complaining of jetlag (Sahakian and Morein-Zamir, 2007). It is likely that physicians will face increasing pressure to prescribe PCEs to healthy individuals, and those who view the role of medicine as helping patients live better or achieve their goals may be open to considering such requests (Chatterjee, 2004; Greely et al., 2008). It is the physicians’ responsibility to detect malingerers, decide whether or not to prescribe drugs for cognitive enhancement off-label, prescribe and monitor appropriately (Hampton, 2007). Otherwise, they risk that patients may decide to approach other doctors or less safe means of obtaining enhancers such as via friends, colleagues or the internet, where little regulation or monitoring is available and safety can be compromised (Califano, 2008; McCabe and Boyd, 2005). In the UK, the Academy of Medical Sciences workgroup specifically identified cognitive enhancers as a topic to be addressed by the Food Standards Agency and the Medicines and Health Care Regulatory Authority (Academy of Medical Sciences, 2008).

Another concern is that the use of cognitive enhancers may be considered cheating, allocating an unfair advantage over others in particular circumstances such as in competitive situations or test taking. Already the popular press has reported the negative opinions of some college students against their peers who use PCEs when studying for exams. Additional concerns pertain to the possibility of being ‘overenhanced’, for example being plagued by unwanted memories. Likewise, given that the effectiveness of PCEs will likely increase in the future, concerns have been raised over alternations in personhood and the risk of becoming a homogeneous society (President’s Council on Bioethics, 2003). Furthermore, our perception of ourselves could change from mechanistic beings, as we may become unable to take credit for our achievements. Additional concerns relate to the fact that PCEs are ‘unnatural’ and that virtues such as motivation and hard work could become outdated with the expectation that everyone could just ‘take a drug’ (for additional discussion of these concerns, please see Chatterjee, 2004; Greely et al., 2008; Wolpe, 2002).

Whilst many of the concerns are already very relevant with the increasing off-label and illicit use of PCEs by young people, such drugs are one method by which individuals can perform better and more effectively and so consequently enjoy more achievements and success. However, we would not want to preclude other methods, for example, extra help in the classroom, smaller classes, and a greater consideration for life/work balance (Sahakian and Morein-Zamir, 2007; Turner and Sahakian, 2006). Currently, PCEs (in particular pharmaceuticals such as modafinil, atomoxetine and methylphenidate) have the potential to provide important clinical benefits and further development in this area is worthy of pursuit. Pharmacogenomics will make it possible to target individuals with safe and effective cognitive enhancers. Pharmacogenomics is the discipline behind how genes influence the body’s response to drugs, which is important for enhancing the efficacy of individualized treatments and reducing medication side effects (see also Roiser et al. 2005). This raises the possibility in future of allowing PCEs to subsets of people who will experience benefits but will likely not experience the adverse effects. Presently, scientists are working together with social scientists, philosophers, ethicists, policy makers and the general public to actively discuss the ethical and moral consequences of cognitive enhancement (Sahakian and Morein-Zamir, 2007). This will go some way to ensuring that technological advances are put to maximal benefit and minimal harm.

Several position and discussion papers have been featured in scientific journals and in the media discussing PCE in the healthy (Greely et al., 2008; Maher, 2008; Sahakian and Morein-Zamir, 2007). With the increased awareness of the ever-growing popularity of cognitive-enhancing drugs, many scientists have expressed positive and negative views on the issue, reflecting the complexity of the debate. Amongst them, Martha Farah of the University of Pennsylvania has commented that ‘‘It would without question improve my quality of life’’ but also considered that others may wonder whether improving productivity through artificial means would undermine the value of hard work. Likewise, as reported in an article in the Daily Mail, scientists such as Michael Gazzaniga, Director for the SAGE Center for the Study of Mind at the University of California Santa Barbara has stated, ‘‘If we can boost our abilities to make up for the ones Mother Nature didn’t give us, what is wrong with that?’’. Other scientists view PCEs in the general population negatively, including Eric Kandel from Columbia University who has stated that using drugs to boost exam scores is ‘‘awful’’. The drugs ‘‘are designed for people with serious problems who really need help’’. Howard Gardner, from Harvard University, has expressed concern that ‘‘We have no idea what these drugs do to other forms of intelligence’’ (e.g., emotional intelligence) (Burne, 2007). Furthermore, Anjan Chatterjee, from the University of Pennsylvania, has raised the valid argument that ‘‘No one has conducted thorough studies about how brain-boosting drugs would affect healthy people after weeks or months of use’’.

The discussion led to Nature conducting an online poll which collected data from 1400 respondents from 60 countries (Maher, 2008). Interestingly, one in five respondents said they had used drugs for non-medical reasons as cognitive enhancers. Of those responding, 52% obtained cognitive-enhancing drugs by prescription, 34% by the internet and 14% by pharmacy. It was unclear whether the prescribed enhancers were diverted from other people’s prescriptions, prescribed for different purposes or at different doses for the user, although in the UK a greater proportion obtained the drugs over the internet compared with the USA. In another online survey conducted in the USA, friends and peers were identified by the majority of university student respondents as the source of prescription drugs (McCabe and Boyd, 2005). This latter finding dovetails with a recent survey reported in the UK amongst Cambridge University students (Lennard, 2009). In the Nature poll, the most popular drug reported in the survey was methylphenidate (Ritalin) with 62% of users, 44% reported taking modafinil, and 15% reported taking beta-blockers (but see Teter et al., 2006 for different findings).

The respondents’ opinions were also informative, with 96% of all respondents thinking that people with neuropsychiatric disorders should be given cognitive-enhancing drugs. In marked contrast, 86% of respondents thought that healthy children under the age of 16 should be restricted from taking cognitive-enhancing drugs. However, 33% of respondents said they would feel pressure to give cognitive-enhancing drugs to their children if other children at school were taking them. The Cambridge Varsity survey, completed by 1000 students, revealed that 1 in 10 had taken a prescription drug for cognitive enhancement (Lennard, 2009). The survey further found large differences between students of the different colleges within the university, as well as between areas of study, with Science and Engineering students being the least likely to take the drugs modafinil, methylphenidate or an amphetamine–dextroamphetamine combination agent (Adderall). This survey complements the attitudes reported in the Nature survey in that a third of respondents said that given the opportunity, they would take a drug to enhance their cognition. Though suggestive, the data above are likely to suffer from selection bias and so should be interpreted with caution.

Conclusions and Outstanding Questions

In summary, we would like to stress that PCEs have considerable potential for improving the lives of individuals with neuropsychiatric and medical disorders, such as AD, schizophrenia, ADHD and those with brain injury. Therefore, PCEs are likely to be developed further and we expect their use to increase. At the same time caution must be exerted, particularly as studies of long-term effects in healthy humans regarding safety and efficacy are urgently required. Moreover, the potential use of PCEs in children with developing brains and the potential for abuse in certain populations must be considered, together with broader societal concerns such as coercion and inequality of access.

Thus, rather than advocate for overall inclusion or exclusion of PCE use in healthy individuals, we would encourage their responsible use. This includes scientists, physicians and policy makers ensuring that easy access to information about the advantages and dangers of using PCEs is available to the public (Sahakian and Morein-Zamir, 2007). Moreover, the public should be encouraged to use other non-pharmacological methods of cognitive enhancement, such as education. Greely and colleagues (2008) recommend that at present policies and limits should be created at the level of professional societies, such as physicians and educators, rather than the law. They further suggest that mentally competent adults should be able to engage in cognitive enhancement using drugs and that regulatory agencies should allow this given the availability of data for safety and efficacy (Greely et al., 2008). However, in order to do this, an evidence-based approach to the assessment of the risks and benefits of cognitive enhancement must be adopted. Additionally, there is a need for large-scale and refined surveys that do not focus necessarily on addiction, and that target populations beyond college students (see also Boyd and McCabe, 2008). However, others propose the formation of new laws and indeed regulatory structures to protect against the potential harms (Fukuyama, 2002).

Careful and critical evaluation of PCEs for the healthy population continues to be a key challenge to policymakers and regulators (Foresight Mental Capital and Wellbeing Project, 2008) This can be viewed within the context of the wider phenomenon of healthy adults taking drugs for other reasons, such as to enhance mood or sleeping habits. The potential for the development of better treatments for the cognitive symptoms in neuropsychiatric disorders and brain injury means that novel PCEs that are safe and effective have the potential to be of significant benefit to such individuals within society. Yet, enforceable policies concerning the use of PCEs to support fairness, protect individuals from coercion and minimize enhancement-related socioeconomic disparities are critical (Greely et al., 2008). This has also been recognized in the Foresight Mental Capital and Wellbeing Report as ‘‘Novel PCEs may prove of great benefit in the future, particularly given the rapidly developing field of pharmacogenomics and the aging population’’ (Foresight Mental Capital and Wellbeing Project, 2008). Ultimately, we too advocate a rational approach to the use of PCEs in order to gain maximum benefits with minimum harms to the individual and to society as a whole. The use of PCE is relevant to everyone and particularly to members of the psychopharmacology scientific community. We hope that by raising the neuroethical issues accompanying the scientific findings, and presenting some of the social implications already taking place, the reader will consider these issues.