Handbook of Clinical Neurology, Vol.

118 (3rd series)

Ethical and Legal Issues in Neurology
J.L. Bernat and R. Beresford, Editors
© 2013 Elsevier B.V. All rights reserved

Chapter 27

The ethics of neuroenhancement

ANJAN CHATTERJEE*
Department of Neurology and the Center for Cognitive Neuroscience, University of Pennsylvania, Philadelphia, PA, USA

STATEMENT OF THE PROBLEM Physicians uncomfortable with enhancements

We can and should celebrate recent progress in the clinical
neurosciences. Our ability to treat diseases, modify their
course, or at least alleviate symptoms has been improving
steadily and we can anticipate more advances to come.
However, in the wake of this progress, we must keep
an eye on unintended consequences of these advances.
One consequence of our ability to improve the function
of the impaired nervous system is the possibility that
we might improve function of the healthy nervous system.
If we can make ourselves better, should we?
“Cosmetic neurology” is the term I used to describe
the practice of using neurologic interventions to improve
movement, mood, and mentation in healthy people
(Chatterjee, 2004, 2006). A scenario in which this prac­
tice is commonplace is not science fiction speculation.
Athletes use anabolic steroids, musicians use beta-
blockers, and students use stimulants commonly. Even
some academics medicate themselves with the presumed
goal of becoming more productive (Sahakian and
Morein-Zamir, 2007; Chatterjee, 2008b).
This chapter focuses on interventions in anticipation
of the fact that physicians will encounter pressure from
“patients” to prescribe treatments for nontherapeutic
uses. In this chapter, I describe interventions available
currently and those that might soon be available. I then
outline the ethical concerns that surround such enhance­
ments and touch on special concerns that arise with
children and soldiers. Despite ethical concerns
associated with enhancements, I argue that the practice
of cosmetic neurology will become widespread
(Chatterjee, 2007). My claim is predictive, not prescrip­
tive. In my view, it is less useful to discuss whether this
practice should occur than to consider what form this
practice might take.
might reflexively wish to rely on a treatment-versus­
enhancement distinction to guide their practice. Therapy
treats disease, while enhancement improves normal
abilities. Since physicians are in the business of treating
disease, they should not prescribe enhancements.
Unfortunately, the distinction between therapy and
enhancement is unclear, particularly when “disease” lacks
clear boundaries and conditions are continuous rather
than categoric. For example, if short people can be “trea­
ted” with growth hormone (Cuttler et al., 1996), should it
matter if they are short because of a growth hormone defi­
ciency or because they had short parents (Daniels, 2000)?
Furthermore, the history of cosmetic surgery to enhance
normal physical attributes suggests that cultural and com­
mercial forces will push physicians to endorse such prac­
tices (Chatterjee, 2007). At the root of cosmetic neurology
is a difficult question for physicians. If one purpose of
medicine is to improve the quality of life of individuals
who happen to be sick, then why not apply this medical
knowledge to those who happen to be healthy?
ENHANCEMENTS
Enhancements fall into three general categories:
improvement of motor systems, cognition, and mood
and affect (Chatterjee, 2004). For a long time, healthy
people have used alcohol, tobacco, chocolate, and caf­
feine to modulate their mental states. Now, prescription
pharmacologic options are increasing and other inter­
ventions are on the horizon. For novel medications, the
effects in clinical populations are often not known and
their efficacy and safety in healthy individuals are rela­
tively unexplored. However, we can anticipate that such
interventions will be increasingly available, and in the
long run probably increasingly efficacious and safe.

*Correspondence to: Anjan Chatterjee, M.D., Department of Neurology and the Center for Cognitive Neuroscience, University of
Pennsylvania, 3 West Gates, 3400 Spruce Street, Philadelphia, PA 19104, USA. Tel: þ1-215-662-4265, Fax: þ1-215-349-5579, E-mail:
anjan@mail.med.upenn.edu
324 A. CHATTERJEE
Movement and Albert, 2004). Presumably, similar effects occur in
healthy subjects. Methylphenidate is used widely in clin­
Medicine can make people stronger, swifter, and more
ical and healthy populations to improve attention, con­
enduring. Professional athletes use anabolic steroids to
centration, spatial working memory, and planning
improve their strength and quickness. Beyond steroids,
(Pary et al., 2002; Weber and Lutschg, 2002; Mintzer
other ways of improving motor performance are avail­
and Griffiths, 2007; Zeeuws et al., 2010). Amphetamines
able. Insulin-like growth factor (IGF) produced by the
also increase people’s willingness to exert effort even
liver may improve the quality of life of people without
when the chances of rewards are low (Wardle et al.,
disease. IGF given to men over the age of 60 for 6 months
2011). Students commonly use amphetamines and their
increased their muscle mass, decreased body fat, and
analogs (McCabe et al., 2005), despite the fact that these
improved skin elasticity (Rudman et al., 1990). In mice,
drugs may sometimes impair performance (Diller, 1996;
injection of recombinant viruses containing the IFG-1
Babcock and Byrne, 2000) and that the actual empiric
gene directly into muscle also increased muscle mass
data in support of their effects are far from clear
and strength and prevented declines observed in
(Smith and Farah, 2011). Newer nonaddictive drugs such
untreated old mice (Barton-Davis et al., 1998). Drugs
as atomoxetine (a selective norepinephrine reuptake
that increase muscle mass in rodents by altering cellular
inhibitor) that probably improve executive control
metabolism could be the fantasy that many have of exer­
(Chamberlain et al., 2009) are likely to increase off-label
cise in a pill (Narkar et al., 2008).
use of such medications. Other stimulants, like modafi­
Maximizing blood oxygenation optimizes muscle
nil, improve arousal and ameliorate deficits of sustained
activity and enhances athletic performance. In the past,
attention associated with sleep deprivation (Lagarde
athletes trained at high altitudes and stored their own
et al., 1995; Caldwell et al., 2000).
blood for later autotransfusions to increase their
Cholinesterase inhibitors also improve attention and
oxygen-carrying capacities (Gaudard et al., 2003).
memory (see Repantis et al., 2010a for a review). These
Human erythropoietin (EPO), used to treat anemia,
medications are used widely in Alzheimer’s disease, and
has been used as a form of athletic “doping”
their use in older people is increasing. The effects of
(Gaudard et al., 2003; Varlet-Marie et al., 2003). Trans­
cholinesterase inhibitors on healthy subjects need more
fusion alternatives, motivated by blood supply shortages
study. However, one intriguing early report suggests
and contaminants, are likely to have implications for per­
an effect in the setting of highly skilled performance.
formance when endurance is critical (Gaudard et al.,
Yesavage and colleagues (2001) reported that commer­
2003). Even sildenafil can increase pulmonary oxygen-
cial pilots taking 5 mg of donepezil for 1 month per­
carrying capacity, which may have performance benefits
formed better than pilots on placebo on demanding
(Ghofrani et al., 2004).
Cessna 172 flight simulation tasks, particularly when
Finally, modulating neural plasticity may enhance
responding to emergencies. Since then these drugs have
learning motor skills. For example, amphetamines in
been reported to improve semantic processing
small doses promote plasticity and accelerate motor
(FitzGerald et al., 2008) and memory (Gr€on et al.,
learning (Walker-Batson et al., 1995; Grade et al.,
2005) and mitigate the effects of sleep deprivation
1998). Their effects are most pronounced when paired
(Chuah and Chee, 2008).
with training, as seen in patients with weakness follow­
Two new classes of drugs, ampakines and cyclic
ing stroke. It is reasonable to expect that amphetamines
adenosine monophosphate (AMP) response element-
used when healthy people learn to swim or ski, or play the
binding protein (CREB) modulators, might improve
piano, might improve their acquisition of these skills.
memory. These drugs capitalize on recent advances in
understanding of the intracellular events that contribute
to structural neural changes associated with the acquisi­
Cognition
tion of long-term memory (Lynch and Gall, 2006).
The fruits of current research in therapy for degenera­ Facilitation of glutamatergic transmission promotes
tive and developmental cognitive disorders are likely long-term potentiation, which is postulated to foster syn­
to overflow into healthy populations. Most pharmaco­ aptic plasticity and memory formation. Ampakines aug­
logic cognitive treatments target the catecholamine ment AMPA-type glutamate receptors by depolarizing
and cholinergic systems. postsynaptic membranes in response to glutamate. Since
The catecholamine effects on neuronal plasticity that N-methyl-D-aspartic acid (NMDA) receptors, crucial to
improve motor learning may also apply to cognitive sys­ induction of long-term potentiation (Kemp and
tems (for recent reviews, see Repantis et al., 2010b). McKernan, 2002), respond to this depolarization, ampa­
Amphetamines improve the effects of speech therapy kines are thought to facilitate the acquisition and consol­
in aphasic patients (Walker-Batson et al., 2001; Klein idation of new memories (see Lynch et al. (2011) for a
 THE ETHICS OF NEUROENHANCEMENT
review). Early studies show that ampakines improve
memory in rats (Granger et al., 1993; Staubli et al.,
1994) and short-term memory in healthy humans
(Ingvar et al., 1997; Wezenberg et al., 2007). They also
attenuate impairments of attention after sleep depriva­
tion (Boyle et al., 2011). The NMDA receptors them­
selves may ultimately be a target of genetic
modification. Mice genetically altered to overexpress
NMDA receptors have superior learning and memory
abilities (Tang et al., 1999).
Neurogenetic studies suggest that CREB is a critical
molecular “switch” in forming short- and long-term
memories (Tully et al., 2003; Benito and Barco, 2010;
Chen et al., 2010). Gene expression is promoted by acti­
vation of CREB, which itself is dependent on NMDA
receptor activation. Specific protein kinases activate
CREB. CREB then sets off a transcription cascade that
produces specific structural changes at the synapse.
Drosophila, genetically altered to overexpress CREB,
demonstrate long-term conditioning to odor-shock pair­
ings after only one exposure, a conditioning that nor­
mally takes 10 trials (Yin et al., 1995). Similar effects
are seen in mammals (Scott et al., 2002). Mice given roli­
pram, a phosphodiesterase inhibitor that enhances
CREB, form long-term memories in fewer than half
the trials needed by untreated mice (Tully et al., 2003).
The search for CREB modulators to enhance memory
is actively under way (Xia et al., 2009).
Mood and affect
We are inundated with mood and affective disorders.
The aisles of drug stores testify to people’s appetites
for mood regulators, such as St. John’s wort, kava kava,
and valerian. Antidepressants, most notably, selective
serotonin reuptake inhibitors (SSRIs), are used widely
for depression, but also for anxiety, obsessive compul­
sive, and oppositional behaviors. Some researchers esti­
mate that between 9.5% and 20% of Americans are
depressed (National Institute of Mental Health, 2003).
SSRIs may selectively dampen negative and not positive
affect (Knutson et al., 1998) and increase affiliative
behavior in social settings (Tse and Bond, 2002).
If SSRIs improve a general sense of wellbeing, their
widespread use seems inevitable.
New treatments for affective illnesses will probably
expand our enhancement possibilities (Holmes et al.,
2003; Salzano, 2003). Blocking glucocorticoids may help
a subset of depressed patients. Corticotropin-releasing
factor (CRF) seems to mitigate long-term stress effects
(Davis, 1998; Walker et al., 2003). Several new ways of
potentially controlling affective states by modulating
neuropeptides are emerging. Neuropeptides are small
proteins that influence how information is processed
325
in the brain and are linked to specific behaviors. Blocking
CRF may blunt the effects of long-term stress. In addi­
tion to CRF, other neuropeptides, like substance P, vaso­
pressin, neuropeptide Y, and galanin, may play a role in
depression and anxiety (McGonigle, 2012). Neuropep­
tide agonists and antagonists that cross the blood–brain
barrier may expand our clinical armamentarium
(Holmes et al., 2003; Holsboer and Ising, 2008). We
may even be able to modulate our emotional states in
more subtle ways. For example, oxytocin and vasopres­
sin might be used to induce trust and promote affiliative
behavior (Kosfeld et al., 2005; Insel, 2010).
Pharmacologic agents can also modulate the way
emotional events are remembered (Cahill, 2003;
Strawn and Geracotti, 2008). In animals, consolidation
of emotional memories is strengthened by epinephrine
and dampened by beta-blockers. Similar effects occur
in healthy people. Subjects given propranolol remember
emotionally arousing stories as if they were emotionally
neutral (Cahill et al., 1994). Propranolol also enhances the
memory of events surrounding emotionally charged
events that are otherwise suppressed (Strange et al.,
2003). In one study, patients in an emergency room given
propranolol after a traumatic event suffered fewer post­
traumatic stress disorder symptoms when assessed
1 month later (Pitman et al., 2002). These trauma-
dampening effects might be increased if propranolol is
given with alpha-1 adrenergic agonists (Shad et al.,
2011). Most people support treating posttraumatic stress
disorder to help individuals who are paralyzed by deeply
disturbing memories, for example, from war or from
sexual and physical assault. However, these studies sug­
gest that less disturbing memories might also be muted,
if we so desired.
NONINVASIVE BRAIN STIMULATION
Noninvasive brain stimulation techniques such as trans-
cranial magnetic stimulation (TMS) and transcranial
direct current stimulation (tDCS) are increasingly being
used in the clinical neurosciences. These technologies
potentially offer nonpharmacologic methods for
enhancement (Hamilton et al., 2011). TMS involves gener­
ating a rapid time-varying magnetic field in a coil of wire
such that a magnetic field penetrates the scalp and skull
and induces a small current in the brain that is parallel
to the plane of the coil. This current depolarizes neuronal
membranes and generates action potentials. Repetitive
TMS (rTMS) involves applying a series of pulses at a pre­
determined frequency. Its effects outlast the duration of
the actual stimulation. rTMS delivered at a low frequency
(0.5–2 Hz) decreases cortical excitability, whereas higher
frequencies (>5 Hz) typically have the opposite effect
(Maeda and Pascual-Leone, 2003). tDCS applies small
326 A. CHATTERJEE
electric currents to the scalp through two surface elec­
trodes. Current flows in through the cortex from the
anode and out through the cathode. Unlike TMS, which
generates action potentials, the weak electric current in
tDCS modulates the resting neuronal membrane poten­
tial. Cathodal stimulation decreases cortical excitability
by hyperpolarizing cortical neurons, and anodal stimula­
tion increases cortical excitability by depolarizing neurons
to subthreshold levels. These effects last from minutes to
hours depending on the intensity, polarity, and duration of
stimulation (Priori, 2003; George and Aston-Jones, 2009).
TMS is more precise than tDCS, spatially and tempo­
rally. These levels of precision lend themselves to differ­
ent applications depending on whether manipulation of a
mental state or process is better accomplished by
focused or distributed stimulation. tDCS is less expen­
sive, more portable, and associated with fewer risks than
TMS, meaning that its access might bypass physicians or
even scientists as gatekeepers.
What enhancement effects can occur with noninvasive
stimulation? TMS and tDCS can transiently improve learn­
ing and memory in healthy individuals. For example, TMS
can improve working memory, the ability to hold and
manipulate information over short periods of time
(Fregni et al., 2005; Ohn et al., 2008). It can improve
complex motor learning when stimulation is directed to
primary motor cortex (Nitsche et al., 2003; Kobayashi
et al., 2004). It can even facilitate learning language.
Anodal tDCS over Broca’s area improves people’s abilities
to learn new object names and novel grammars (Fl€ oel et al.,
2008; Sparing et al., 2008; De Vries et al., 2010).
The evidence for enhancing more general complex
problem-solving abilities with noninvasive brain stimula­
tion is beginning to accumulate. In one study, tDCS of
the left dorsolateral prefrontal cortex improved perfor­
mance on the remote association test, a task linked to
creative thinking, executive function, and general intel­
ligence (Sparing et al., 2008). Snyder (2009) has even
argued that inhibition of the left anterior temporal lobe
(LATL) with brain stimulation enhances perception by
interfering with semantic networks that normally impose
constraints on sensory processing. He suggests that this
pattern of inducing neural activity might underlie savant
syndromes and could be reproduced with noninvasive
stimulation. By his logic, suppressing the LATL
increases access to less processed information, improv­
ing abilities on tasks such as drawing, proofreading, and
numerosity judgments.
TMS to treat depression (George et al., 2000; Martin
et al., 2003) was approved by the Food and Drug Admin­
istration (FDA) in 2008. rTMS over the prefrontal cortex
even helps some patients who have not responded to anti­
depressant medications. Evidence for the efficacy of
tDCS in treating depression is preliminary, but also
promising (Nitsche et al., 2009). Unilateral stimulation
of the prefrontal cortex can induce transient changes
in mood in healthy individuals as well (George et al.,
1996; George, 2003). For unclear reasons, mood changes
induced by high-frequency rTMS in healthy persons
seem to show a pattern opposite to that seen in depressed
patients. Elevations of mood are associated with right-
sided excitation and depression of mood with left-sided
excitation. Non-invasive stimulation, especially tDCS,
may very well be used widely to modulate mood in the
healthy if this intervention is viewed as safer than drugs
and access does not depend on going through a physician
or a bureaucratized healthcare system.
ETHICAL DILEMMAS
Regardless of the means by which enhancements are
induced, they raise deep ethical dilemmas. These
dilemmas center on four major concerns: safety, charac­
ter and individuality, distributive justice, and coercion.
Safety
Virtually all medications have potential side-effects that
range from minor inconveniences to severe disability or
death. For example, amphetamines, often used for cogni­
tive enhancements, have FDA black box warnings, partic­
ularly in regard to the risk of addiction and serous cardiac
side-effects, including sudden death (Chatterjee, 2009).
Physicians, not surprisingly, tend to be most concerned
about safety of enhancements given their professional
roles (Banjo et al., 2010). However, recent large-scale
studies do not find greater cardiovascular side-effects
of stimulants as compared to unmedicated control sub­
jects (Cooper et al., 2011; Habel, 2011) and to some extent
mitigate this concern.
Regardless of the relative dangers, in disease states
one weighs risks against potential benefits. A patient with
glioblastoma multiforme might be willing to endure toxic
chemotherapies because the alternative is so grim. In
healthy states any risk seems harder to accept because
the alternative is normal health. For some interventions
the risks are known or suspected. EPO improves endur­
ance but increases the risk of stroke. Modafinil enhances
alertness for some cognitive tasks but may compromise
performance on others (Caldwell et al., 2000). Genetically
modified mice may have terrific memories (Tang et al.,
1999) but are more sensitive to pain (Tang et al., 2001).
A more subtle version of the safety concern is one of
trade-offs rather than side-effects. Would cognitive
enhancement in one cognitive process be accompanied
by detriments to others? For example, medications that
enhanced attention and concentration might conceivably
limit imagination and creativity (but see Farah et al.,
2009). Other possible trade-offs are ways in which
 THE ETHICS OF NEUROENHANCEMENT
enhancing long-term memory could impair working
memory: enhancing consolidation of long-term memo­
ries might disrupt the flexibility of those memories to
respond to a changed environment and alter behavior
(Schermer et al., 2009).
Character and individuality
This concern takes two general forms, one about eroding
character and the other about altering the individuals and
its implications for notions of authenticity and person­
hood. The concern about erosion of character draws on
a “no pain, no gain” belief (Chatterjee, 2008a, b). Many
people believe that struggling with pain builds character,
and eliminating that pain undermines good character.
Similarly, people often think that improving without
doing the work is cheating and such cheating cheapens
us (Kass, 2003b). To some extent, the question of cheating
depends on whether we emphasize the process or the out­
come. Goodman argues that in situations where outcomes
are important and the activity is not a zero-sum game,
enhancements do not cheapen us (Goodman, 2010).
While the concerns about character run deep, they are
mitigated by several factors. Which pains are worth the
hypothetic gains they bring? We live in homes with cen­
tral heating and air, eat food prepared by others, travel
vast distances in short times, take Tylenol for headaches,
and H2-blockers for heartburn. Perhaps these conve­
niences have eroded our collective character and cheap­
ened us. But few choose to turn back. There is a long
medical history of ethical concerns of using anesthesia
to dampen a normal physical pain – that of childbirth
(Chatterjee, 2008a). The concerns were similar to those
now raised for the treatment of psychologic pain. Yet,
in many environments people make their own choice
about whether to use anesthesia, without the choice
being particularly emotionally charged or regarded as
ethically complex. Perhaps our collective reaction to
intervening in normal psychologic pain will evolve
similarly.
A fundamental concern is that chemically changing the
brain threatens our notion of personhood. The central
issue may be that such interventions threaten essential
characteristics of what it means to be human (Kass,
2003a). For example, would selectively dampening the
impact of our painful memories change who we are, if
we are in some sense the sum of our experiences? This
is a difficult issue to grapple with, and consensus on
the essence of human nature may be elusive
(Fukayama, 2002; Wolpe, 2002; Elliott, 2003b; Henry
et al., 2007; Kolber, 2011). Invasive surgical procedures
such as sex change operations are used to express one’s
individuality. Elliott (2003a), in reviewing such practices,
suggests that “in America, technology has become a way
327
for some people to build or reinforce their identity (and
their sense of dignity) while standing in front of the social
mirror.” However, the search and desire for an authentic
self probably drive both the desire for and the worry about
consequences of enhancement (Elliott, 2011).
Distributive justice
If we can enhance ourselves, who gets to do so? New
drugs are expensive and there is no reason to expect that
insurance companies or the state (in the United States)
will pay for nontherapeutic interventions. Only those
who can afford to pay privately would get enhance­
ments. A familiar counter to the worry of widening ineq­
uities is that this is not a zero-sum game. With widening
disparities, even those at the bottom of the hierarchy
receive some benefit and improve from their previous
state. This argument assumes that an absolute level of
quality, rather than a recognition of one’s relative place,
determines people’s sense of wellbeing. However,
beyond worries about basic subsistence, wellbeing is
mostly affected by expectations and relative positions
in society (reviewed by Frank, 1987).
One might argue that the critical issue is access, and
not availability (Caplan, 2003). If access to such
enhancements were open to all, then differences might
even be minimized. This argument may have logical
merit, but in practice (in the United States) it skirts the
issue. We tacitly accept wide disparities in modifiers
of cognition, as demonstrated by the acceptance of ineq­
uities in education, nutrition, and shelter. Furthermore,
new nonpharmacologic technologies like tDCS are cheap
and relatively safe and do not need a physician to serve
as a gatekeeper.
Coercion
The concern here is that matters of choice may evolve into
conditions of coercion. Coercion takes two forms. One is
the implicit coercion to maintain or better one’s position in
some perceived social order. Such pressure increases in a
“winner-take-all” environment in which more people
compete for fewer and bigger prizes (Frank and Cook,
1995). Many professionals work 60, 80, or more than
100 hours a week without regard to their health and hearth.
Emergency department residents use zolpidem especially,
but also modafinil, to regulate sleep and effectiveness
(McBeth et al., 2009). Athletes take steroids to compete
at the highest levels and children at high-end preparatory
schools take methylphenidate in epidemic proportions
(Hall, 2003). Not to take advantage of enhancements
might mean being left behind. Students frequently refer
to academic assignments or grades as reasons to take
amphetamines (Arria et al., 2008; DeSantis et al., 2008).
In a U.S. survey from 2005, nonmedical uses of
328 A. CHATTERJEE
stimulants ranged from 0 to 25%, and were highest in
competitive colleges (McCabe et al., 2005). These prac­
tices are not confined to American students and are also
being reported in Europe (Schermer et al., 2009).
A second form of coercion, which has received less
attention, is the explicit demand of superior perfor­
mance by others. Such coercion could take regulatory
forms. For years, those in the armed forces have been
encouraged to take enhancements “for the greater
good.” Might this logic extend to civilian domains?
Yesavage and colleagues’ (2001) findings that pilots tak­
ing donepezil performed better in emergencies than
those on placebo could have wide implications. If these
results are reliable and significant, should pilots be
expected to take such medications? Can airline execu­
tives require this of pilots? Would they offer financial
incentives to pilots willing to take these medications?
Closer to home, should medical students and post-call
residents take stimulants to attenuate deficits of sus­
tained attention brought on by sleep deprivation (Webb
et al., 2010)? Could hospital administrators require this
practice? How about insurance companies or patients?
SPECIAL POPULATIONS
An important factor in navigating the ethics of enhance­
ment is the recognition and respect for a person’s auton­
omy. There are two situations in which a different sense
of autonomy potentially alters the balance of consider­
ations. Children are by definition less autonomous than
adults. Military personnel voluntarily relinquish some of
their individual autonomy to serve a greater communal
good. How do the ethical concerns about enhancements
apply to children and soldiers?
Children
Children face the same pressures to use enhancements
that adults experience. Many children, especially in
affluent environments, have demanding social sched­
ules, sports commitments, and other extracurricular
activities that are added on to burdensome levels of
schoolwork. Competition in some social strata begins
very early, where parents compete to get their children
into “the best” preschool. In this pressured environment,
it is not surprising that the demand for enhancements has
risen over the last few years (Johnston et al., 2006). In
2005, 7.4% of eighth-graders reported trying amphet­
amines without medical instruction (Johnston et al.,
2006). Physicians are writing more prescriptions for
psychotropic drugs, especially stimulants and antide­
pressants, to young people, often without a clear diagno­
sis of a mental illness (Thomas et al., 2006). From
2002 to 2010 physicians wrote fewer prescriptions for
antibiotics, and 46% more for stimulants. Methylpheni­
date was the most commonly written prescription for
adolescents aged 12–17 (Chai et al., 2012).
The general acceptance of enhancement use to
improve performance in academic, social, and work set­
tings, especially among nonphysicians (Greely et al.,
2008; Schermer et al., 2009), is likely to trickle down
to young people. The use of such “study aids” is not
given a second thought in some settings. Estimates of
nonprescription use of stimulants were below 0.5% until
1995 across the age range from high school to adults.
Since the mid-1990s, 2.5% of high school students, col­
lege students, and young adults consistently report non­
prescription use of stimulants. College student stimulant
use rates range from 5% to 50% (Smith and Farah, 2011).
Data from the Monitoring the Future Survey (monitor­
ingthefuture.org) suggest that young people use differ­
ent psychotropic prescription drugs, including
tranquilizers, painkillers, stimulants, and hypnotics,
for nonmedical purposes (Johnston et al., 2006). These
drugs are used recreationally and to enhance perfor­
mance (Teter et al., 2005; Friedman, 2006). Access to
such medications is not a major impediment. University
chat sites and listserves make prescription drugs avail­
able for nonmedical use (Talbot, 2009). Up to one-fifth
of all children, adolescents, and young adults prescribed
attention deficit hyperactivity disorder medications in
the United States give or sell their medications to other
students (Poulin, 2001).
Ethical concerns for the use of enhancements in chil­
dren take on added force when considering safety,
authenticity, and autonomy. The nervous system is still
developing and long-term biologic impact of enhance­
ments on neural rewards systems is unclear (Kim
et al., 2009). Long-term safety issues for the developing
nervous system are not known. The Director of the U.S.
National Institute for Drug Abuse voiced concern that
“nonmedical” use of methylphenidate could lead to
addiction (http://www.medicalnewstoday.com/articles/
137454.php). Cardiovascular risks have been a concern
and resulted in the FDA black box warnings for stimu­
lants. However, since the original warning, two studies
with large cohorts (Cooper et al., 2011; Habel, 2011) have
not found increased adverse effects with stimulants
compared to unmedicated control participants, perhaps
mitigating this concern.
Another concern is the development of children’s
character and notions of authenticity. Potential threats
include altering young people’s developing sense of per­
sonal identity, particularly the notion of an “authentic”
(unmedicated) self, and their sense of personal respon­
sibility. The concern arises because stimulants alter their
reward circuitry (Kim et al., 2009) and alter behavior,
motivation, attention, and interaction with others. Such
 THE ETHICS OF NEUROENHANCEMENT
concerns are countered by observations that young peo­
ple with ADHD who take stimulant medication feel
greater agency when on medication in determining the
outcome of their immediate actions and in planning their
future (Singh, 2007). Typically, they use stimulants for
short-term specific goals and not as a daily regimen mit­
igating concerns of the effects of long-term chronic use
(Singh et al., 2010).
Concerns about coercion take on special significance
with children because of their lack of autonomy. Young
people typically give assent rather than fully informed
consent to treatment or participation in research. This
distinction acknowledges the fact that they are not fully
autonomous. Nonetheless, young people often under­
stand their medical conditions and make reasonable
treatment decisions from a young age (Kuther and
Posada, 2004; Miller et al., 2004). Decisions involving
long-term risks may be particularly challenging for
younger children because they involve calculation of
future risk–benefit ratios (Singh et al., 2010). Parents
can be driven by performance pressures or goals to pro­
duce highly successful children even at the expense of
the child’s physical or mental health. These factors can
have a coercive influence on the use of enhancements
in young people. Schools can amplify such coercive
forces. Teachers are often the first to suggest to parents
that a child might benefit from stimulant treatment (Sax,
2003). Schools sometimes allegedly exert so much pres­
sure on families to pursue stimulant drug treatment that
some U.S. states have passed legislation to make it illegal
for schools to accuse parents of educational neglect for
refusing to give their children stimulants (Singh and
Kelleher, 2013).
Soldiers
While children’s autonomy is limited because they are
not yet adults, members of the military voluntarily give
up some of their autonomy when they choose to serve.
Members of the military can also find themselves in dan­
gerous situations that are rarely experienced by civilians
and this factor also has an impact on the ethical checks
and balances in play. How should we think about
enhancements in the military (Russo et al., 2013)?
The ethical concerns of safety and coercion take on
their own unique form when it comes to the military
(Moreno, 2006; Russo et al., 2008). Safety cuts both
ways. In some situations, rarely applicable to civilians,
using enhancements might be safer than not. Russo
and colleagues (2013) offer two scenarios in which the
use of enhancements might be advisable. Servicemen
often fly over many time zones and have to perform
extended duties on arrival. They often dread the flight
itself and may be anxious about anticipated dangers.
329
A hypnotic or anxiolytic to help them rest and prepare
for whatever lies ahead might be justified and help them
perform their duties more safely. Another situation
might be when a group of soldiers in hostile territory
are separated from their unit. In such a situation, soldiers
would need to be alert and vigilant under sleep-deprived
conditions. Using amphetamines or drugs like modafanil
might actually improve the group’s chances of survival.
The safety risks of using enhancements include the pos­
sibilities of addiction and misuse of these medications,
especially for long deployments when soldiers may be
bored for extended periods in between military engage­
ments. It also might be difficult to instruct them at proper
dosage and use in emergencies. Finally, whether such med­
ications affect decision-making capacities are not known.
Concerns have been raised about the effects of amphet­
amines on judgment; for example, the trial of American
pilots who killed four Canadians in the Tarnack Farms
friendly fire incident considered the fact that the pilots were
encouraged to use amphetamines (Friscolanti, 2005). Such
a defense could undermine the Uniformed Code of Mili­
tary Justice if defense attorneys successfully argue that ser­
vice members are not responsible for their actions
committed in pharmacologically altered mental states.
The military takes some pains to avoid explicitly coerc­
ing soldiers to use enhancement (Russo et al., 2013). How­
ever, the military is clearly an organization where
conformity is admired and peer pressure is forceful.
Under these circumstances, if the cultural norm were to
use enhancements, perhaps encouraged by officers, many
soldiers would acquiesce. Wilson, of the U.S. Military
Academy, thinks that military members in small close-knit
units and dependent upon one another for their individual
and collective survival would feel undue pressure to use
an agent that they are told will enhance their war fighting
abilities. However, he also worries that a soldier who is or
feels forced to take an enhancement medication may
become alienated and this situation could produce irrevo­
cable psychologic harm (Wilson, 2004).
In Beyond Therapy: Biotechnology and the Pursuit of
Happiness, Leon Kass (2003a) of President G.W. Bush’s
Council on Bioethics opined:
There may indeed be times when we must override
certain limits or prohibitions that make sense in
other contexts — offering steroids to improve the
strength of service members while rejecting them
for athletes, offering amphetamines to improve the
alertness of fighter-pilots while rejecting them
for students, offering anti-anxiety agents to steady
the hands of surgeons while rejecting them for
musicians. When we override our own bound­
aries, we do so or should do so for the sake of
the whole, and only when the whole itself is at
330 A. CHATTERJEE
stake, when everything human and humanly digni­
fied might be lost. And we should do so only uneas­
ily, overriding boundaries rather than
abandoning them, and respecting certain ultimate
limits to ensure that men remain human even in
moments of great crisis. For example: Even if they
existed, and even in times of great peril, we might
resist drugs that eliminate completely the fear or
inhibition of our service members, turning them
into killing machines (or dying machines),
without trembling or remorse. Such biotechnical
interventions might improve performance in a just
cause, but only at the cost of making men no dif­
ferent from the weapons they employ.
The Council identifies the critical tension here between two
poles – the recognition that in some situations the auton­
omy of an individual might be sacrificed for a greater good
at one end, and the importance of not losing sight of the
humanity of individual soldiers at the other end.
FUTURE CONSIDERATIONS
The armamentarium of drugs and now newer noninva­
sive stimulation technologies that could be used to
enhance healthy people is growing. We can anticipate
that this growth will continue for the indefinite future.
While the ethical concerns run deep, some form of this
practice is here, and its growth seems inevitable. Coun­
tervailing social pressures are overwhelming. The print
media and bioethicists generally discuss enhancements
positively (Forlini and Racine, 2009). Individuals overes­
timate the efficacy of enhancers like methylphenidate or
modafanil (Repantis et al., 2010b). Pharmaceutical com­
panies have significant economic incentives in expand­
ing their markets to healthy individuals.
Treatments to enhance normal abilities are likely to be
paid for privately. If social pressures encourage wide use
of medications to improve quality of life, then pharma­
ceutical companies stand to make substantial profits and
they are likely to encourage such pressures. According to
Elliott (2003a), in 2001 GlaxoSmithKline spent $91 mil­
lion dollars in direct advertising to consumers for its
medication Paxil, more than Nike spends on its top shoes.
Gingko biloba, despite its minimal effects on cognition
(Solomon et al., 2002), is a billion-dollar industry. Phar­
maceutical companies, undoubtedly encouraged by sales
of Viagra, are not oblivious to the marketing possibilities
of “interventions” applicable to the entire population
(Langreth, 2002; Hall, 2003).
Physicians who hope that clinical norms will serve as a
meaningful brake on dispensing enhancement medica­
tion to healthy individuals are likely to be disappointed.
The historic precedent of the widespread use of cosmetic
surgery demonstrates a willingness of physicians to
engage in nontherapeutic practices. With appropriate
incentives and cultural frameworks in place, cosmetic
surgery went from being considered frivolous in the
early part of the 20th century to logging over nine million
procedures in 2004 by licensed physicians (Chatterjee,
2007) and over 12 million by 2009. With easy access to
medications, especially over the internet, it is highly
unlikely that enhancements will not be used widely.
Technologies like tDCS do not even require physicians
to be involved in the choice to try enhancements.
Strict prohibition of the use of enhancements is
unlikely to serve as an effective policy. This approach
would simply move the market for such medications
underground and inhibit guiding the actual practice of
cosmetic neurology in an informed way. Physicians
should continue to play an active role, although we
may need to think beyond traditional disease treatment
models of care (Chatterjee, 2004; Bostrom, 2008;
Ravelingien et al., 2009; Synofzik, 2009). Approaching
enhancement as a public health issue may also move
the discussion forward (Outram and Racine, 2011).
Establishing professional norms molded by cultural
values and community discussions will be needed. The
American Academy of Neurology has begun this pro­
cess. Its guidance does not prohibit neurologists from
prescribing medications for enhancements in adult
patients (Larriviere et al., 2009).
Clearly, we need adequate research in the use of
enhancement medication in nondiseased individuals.
Whether results from diseased populations will general­
ize to normal individuals is not clear. For example,
would the benefits of stimulants for individuals with
attention deficit disorders generalize to those without
attention deficits? What cognitive trade-offs might
occur? There are significant impediments to acquiring
relevant data necessary for individuals to make a
well-informed choice. Institutional review boards may
be reluctant to endorse such research. After all, why
should the institution accept any risk of severe side-
effects, however small that risk might be, when partic­
ipants are healthy? Additionally, who would fund such
research? In the United States, the major source of
biomedical research funding, the National Institutes
of Health have been reluctant to fund research into non-
therapeutic interventions.
Policies to maximize benefits and minimize harm
would be helpful to mitigate the ethical concerns raised
by enhancements (Appel, 2008; Greely et al., 2008).
Enforceable policies concerning the use of cognitive-
enhancing drugs to support fairness, protect individuals
from coercion, and minimize enhancement-related
socioeconomic disparities should be implemented. Physi­
cians, educators, regulators, and others professional
groups will need to establish their own “positions” as cul­
tural norms are debated and eventually cohere.
 THE ETHICS OF NEUROENHANCEMENT
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