These letters respond to the Commentary \u27Towards responsible use of cognitive-enhancing drugs by the health\u27 by Henry Greely and colleagues. (Nature 456, 702-705; 2008

Chatterjee, Anjan

English

ScholarlyCommons@Penn

University of Pennsylvania ScholarlyCommons Neuroethics Publications Center for Neuroscience & Society 1-2009 Correspondence: A Medical View of Potential Adverse Effects Anjan Chatterjee Follow this and additional works at: https://repository.upenn.edu/neuroethics_pubs Recommended Citation Chatterjee, A. (2009). Correspondence: A Medical View of Potential Adverse Effects. Retrieved from https://repository.upenn.edu/neuroethics_pubs/82 Nature, 2009, 29 January, Vol 338 Further discussion of the Commentary and these Correspondence contributions is welcome at Nature Network. Please cisit http://tinyurl.com/6nyu29. This paper is posted at ScholarlyCommons. https://repository.upenn.edu/neuroethics_pubs/82 For more information, please contact repository@pobox.upenn.edu. Correspondence: A Medical View of Potential Adverse Effects Abstract These letters respond to the Commentary 'Towards responsible use of cognitive-enhancing drugs by the health' by Henry Greely and colleagues. (Nature 456, 702-705; 2008) Comments Nature, 2009, 29 January, Vol 338 Further discussion of the Commentary and these Correspondence contributions is welcome at Nature Network. Please cisit http://tinyurl.com/6nyu29. This journal article is available at ScholarlyCommons: https://repository.upenn.edu/neuroethics_pubs/82 Risks and benefits may turn out to be finely balancedSIR — This Commentary is the latest in a series of expert-led deliberations on the prospects and implications of cognitive-enhancing drugs (see, for example, refs 1–3). Much of the debate on enhancement, as illustrated by the Commentary, is highly speculative and rests on assumptions that are not well grounded in evidence or experience. There are three key problematic areas.First, efficacy — the claimed and assumed benefits are often exaggerated. Careful analysis of trial data suggests that any cognitive-enhancing effects of these drugs in healthy humans are at best modest and mixed, and at worst little better than placebo.Second, safety — very few drugs are completely without adverse effects, especially when used chronically. In the absence of data on the long-term safety implications of these drugs, it is premature to be helping society “accept the benefits of enhancement” when the balance between risk and benefit might be much narrower than assumed.Third, demand — there is little empirical evidence that large numbers of people will use (or are interested in using) enhancers on a routine basis. There is partial or anecdotal evidence of use in specific situations (for example, examinations), but equally, other partial or anecdotal evidence suggests considerable resistance to chronic use among the general public.If enough positive assumptions are made about these key issues, then almost any technology can look attractive or inevitable. The speculation offered in the Commentary may be of interest to academic debates in philosophy. But what is needed is realism, based on a more sober evidence-based assessment that does not create unrealistic expectations about either the potential benefits, or the threats, to individuals and society.Simon J. Williams Department of Sociology, University of Warwick, Coventry CV4 7AL, UK e-mail: s.j.williams@warwick.ac.ukPaul Martin Institute for Science and Society, University of Nottingham, University Park, Nottingham NG7 2RD, UK1. Academy of Medical Sciences Brain Science, Addiction and Drugs (AMS, 2008).2. British Medical Association Boosting Your Brain Power: Ethical Aspects of Cognitive Enhancements (BMA , 2007). 3. Foresight Drugs Futures 2025? (UK Department of Trade and Industry, 2005).Much ado about cognitive enhancementSIR — Henry Greely and colleagues call for answers to several controversial questions regarding the use of drugs by healthy people to boost cognitive performance. The most important scientific and ethical concern they raise is safety, not least because the pressure that leads people to enhance their performance might also be a crucial trigger to mental disorder. This is particularly likely when combined with sleep deprivation and anxiety caused by aggressive competition, as we have already learned from the indiscriminate use of amphetamines.However, it would not be surprising if the repurposing of these drugs has less of an impact than expected by some and feared by others. Myriad personality traits are just as important as memory or ‘intelligence’ in the overall scheme of a successful life. Studies of gifted or ‘savant’ children show that self-confidence, discipline, focus, drive, resilience and social skills are highly complex personality traits, often found in successful people (see, for example, E. W inner Gifted Children: Myths and Realities; Basic Books, 1996).Using medications to improve cognitive performance might be relevant in the short term. But a fully successful future will always depend on two very singular human features: eagerness to excel and setting a high standard of achievement.João Ricardo Oliveira Neuropsychiatry Department and Keizo Asami Laboratory, Federal Universityof Pernambuco, 50670-901, Recife-PE, BrazilA medical view of potential adverse effectsSIR — Most seasoned physicians have had the sobering experience of prescribing medications that, despite good intentions, caused bad outcomes. They would call for louder notes of caution than those expressed in this Commentary when considering the safety of ‘cognitive-enhancing’ drugs such as Ritalin and Adderall. The authors do not mention the US Food and Drug Administration warning on the packets of both of these drugs. Printed in capitals in a black box, it includes phrases such as: “amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence …M isuse of amphetamine may cause sudden death and serious cardiovascular adverse effects.” This warning does not cover other rare but serious side effects, such as Stevens–Johnson syndrome (a serious skin reaction) or toxic psychosis. Furthermore, the incidence of serious cardiac arrhythmias is likely to be higher in older people with incipient cardiovascular disease — likely consumers of ‘healthy’ enhancement. Further reason for caution in advocating neuroenhancers is the disproportionate advantage the These letters respond to the Commentary ‘Towards responsible use of cognitive-enhancing drugs by the healthy’ by Henry Greely and colleagues (Nature 456, 702–705; 2008).532NATURE|Vol 457|29 January 2009OPINIONCORRESPONDENCE??????? ?????????????????????? ?????? ??????????????????Early scientific visitors found mammalian fossils awaiting discovery in apothecary shops Xu Xing on the discovery of the Peking Man fossils, page 538 drugs, if effective, would confer on the wealthy. The authors’ acknowledgment of existing disturbing inequities does not mean that we should add more. A responsible position would be to call for a moratorium on the use of enhancers until enforceable policies to minimize socioeconomic disparities are in place, research into the use and impact of these drugs is completed, information on risks and benefits is broadly disseminated — and physicians, educators and regulators have articulated professional normative positions. Anjan Chatterjee Department of Neurology and Center for Cognitive Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USAe-mail: anjan@mail.med.upenn.edu Recall of learned information may rely on taking drug again SIR — Henry Greely and colleagues identify critical areas of public discussion about perceptions and use of drugs that are alleged or expected to improve cognition. Stimulants and other drugs proposed as potential cognitive enhancers are known to create profound state dependence, a phenomenon in which information or associations learned while ‘under the influence’ of a drug will later be remembered or used only when the learner has again taken the drug. Thus, individuals who use amphetamines to improve their learning of new information may indeed learn slightly faster or with less effort than those who do not use such drugs. Later, however, they may not remember or use the learned information unless they take amphetamines or related drugs again. How and when state dependence occurs has been studied extensively in humans and other animals, in well-controlled learning tasks in laboratory settings. State dependency of cognitive enhancers would dramatically influence drug use, the permanence of learning and the ability to use information in new conditions. Indeed, state dependence can complicate clinical use of pharmacotherapies for such disorders as anxiety and attention-deficit hyperactivity disorder.Greely and colleagues note critical research and policy questions that societies must consider to shape expectations about putative cognitive enhancers. We urge that the discussion includes the known and profound state-dependent effects of these agents.Alice M. Young Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, 3601 4th Street, STOP 6592, Lubbock, Texas 79430, USAe-mail: alice.young@ttuhsc.edu Francis C. Colpaert Institut de Recherche Pierre Fabre, 3, rue des Satellites, BP 94244, 31432 Toulouse Cedex 4, France Patterns of drug use have varied throughout historySIR — Current issues are assessed by Henry Greely and colleagues, but their Commentary contains a bias consistent with current Western culture. The use of these drugs is probably older than recorded history. They have often been used regardless of social convention or rules — and have had impacts on societies. In the 1960s, ‘mind-altering drugs’ had a different connotation from the present, exemplified by Timothy Leary’s “Turn on, tune in and drop out” philosophy. Drugs such as marijuana and LSD were said to enhance individual thinking and creativity, but research both on the mental effects of these drugs and on their use has decreased. Since then, the use of mind-altering drugs has shifted towards enhancing performance, usually with amphetamine analogues. It seems that these are becoming acceptable when used for the goal of efficient production in standardized ways.Don Burnap 11 Oakland Street, Rapid City, South Dakota 57701, USA The five preceding letters are a selection of many comments on this Commentary that were submitted to Correspondence. Many other reactions from readers have been posted in a long and lively online discussion forum at Nature Network, including the following anonymous contributions.Careful use helps me do better research, and society benefitsSIR — I commend the authors of this Commentary on what I think is a fair and insightful piece. I suspect many of the negative commenters are guilty of default outrage without careful thought.I find that my own occasional, metered use of these drugs can make astounding increases in my ability as a researcher — which results in tangible benefit to society. It’s not a competition, I’m not taking an exam. I’m doing research; research that I hope may one day improve the lives of many. I exercise, sleep, eat well and I drink coffee. Yet sometimes that significant extra boost allows me to spend 12 hours successfully working through mathematics that for weeks I was previously unequal to solving. Why is this the act of a social criminal?Current attitudes towards such drugs seem to be that they are good if you need them to become equal, but wrong if you want to become more than equal. Can we really be so quick to condemn a striving to better ourselves? Should we tell brighter students to hold back to the median? I think not. This issue is not black and white; it requires the careful grey-scale considerations the Commentary authors recommend.It is true that many physicians and biomedical researchers have placed themselves in quite a tangled conflict-of-interest web, and that this compromise can be dangerous. Some of the authors of this Commentary may have some conflict of interest, which thankfully Nature requires authors to disclose. However, that possible conflict of interest does not release you, the reader, from your obligation to rationally and carefully consider their argument. They are not wrong just because some of them consult for pharmaceutical companies. Enhancement means a broader role for physiciansSIR — This Commentary raises a wider issue of perceived responsibility. The traditional role of physician as healer does not sit with the category of enhancement. Plastic surgery serves as a good analogy here, with views remaining varied on the ultimate responsibility. But with planned, novel, pharmacological intervention, physicians must surely be party to the cause, and thus a broadening of their role would be necessary.Ultimately, the call for risk–benefit research and a fuller understanding of mechanisms is therefore welcome, but the real beneficiaries, at least in the short term, are likely to be dominated by the genuinely needy — neurological and psychiatric patients. These groups have had their needs for cognitive enhancement unmet for far too long.Further discussion of the Commentary and these Correspondence contributions is welcome at Nature Network. Please visit http: // tinyurl.com/6nyu29 to have your say.533NATURE|Vol 457|29 January 2009 OPINION29.1 Correspondence.indd NS Colin.indd   533 26/1/09   17:29:28??????? ?????????????????????? ?????? ??????????????????

Correspondence: A Medical View of Potential Adverse Effects

Kosmopolis

University of Pennsylvania 
ScholarlyCommons 
Neuroethics Publications Center for Neuroscience & Society 
1-2009 
Correspondence: A Medical View of Potential Adverse Effects 
Anjan Chatterjee 
Follow this and additional works at: https://repository.upenn.edu/neuroethics_pubs 
Recommended Citation 
Chatterjee, A. (2009). Correspondence: A Medical View of Potential Adverse Effects. Retrieved from 
https://repository.upenn.edu/neuroethics_pubs/82 
Nature, 2009, 29 January, Vol 338 
Further discussion of the Commentary and these Correspondence contributions is welcome at Nature Network. 
Please cisit http://tinyurl.com/6nyu29. 
This paper is posted at ScholarlyCommons. https://repository.upenn.edu/neuroethics_pubs/82 
For more information, please contact repository@pobox.upenn.edu. 
Correspondence: A Medical View of Potential Adverse Effects 
Abstract 
These letters respond to the Commentary 'Towards responsible use of cognitive-enhancing drugs by the 
health' by Henry Greely and colleagues. (Nature 456, 702-705; 2008) 
Comments 
Nature, 2009, 29 January, Vol 338 
Further discussion of the Commentary and these Correspondence contributions is welcome at Nature 
Network. Please cisit http://tinyurl.com/6nyu29. 
This journal article is available at ScholarlyCommons: https://repository.upenn.edu/neuroethics_pubs/82 
Risks and benefits 
may turn out to be 
finely balanced
SIR — This Commentary is the 
latest in a series of expert-led 
deliberations on the prospects 
and implications of cognitive-
enhancing drugs (see, for 
example, refs 1–3). Much of the 
debate on enhancement, as 
illustrated by the Commentary, 
is highly speculative and rests 
on assumptions that are not 
well grounded in evidence or 
experience. There are three key 
problematic areas.
First, efficacy — the claimed 
and assumed benefits are often 
exaggerated. Careful analysis 
of trial data suggests that any 
cognitive-enhancing effects of 
these drugs in healthy humans 
are at best modest and mixed, 
and at worst little better than 
placebo.
Second, safety — very few 
drugs are completely without 
adverse effects, especially when 
used chronically. In the absence 
of data on the long-term safety 
implications of these drugs, 
it is premature to be helping 
society “accept the benefits of 
enhancement” when the balance 
between risk and benefit might be 
much narrower than assumed.
Third, demand — there is little 
empirical evidence that large 
numbers of people will use (or 
are interested in using) enhancers 
on a routine basis. There is partial 
or anecdotal evidence of use in 
specific situations (for example, 
examinations), but equally, 
other partial or anecdotal 
evidence suggests considerable 
resistance to chronic use among 
the general public.
If enough positive assumptions 
are made about these key issues, 
then almost any technology 
can look attractive or inevitable. 
The speculation offered in the 
Commentary may be of interest to 
academic debates in philosophy. 
But what is needed is realism, 
based on a more sober evidence-
based assessment that does not 
create unrealistic expectations 
about either the potential benefits, 
or the threats, to individuals and 
society.
Simon J. Williams Department of 
Sociology, University of Warwick, 
Coventry CV4 7AL, UK 
e-mail: s.j.williams@warwick.ac.uk
Paul Martin Institute for Science and 
Society, University of Nottingham, 
University Park, Nottingham 
NG7 2RD, UK
1. Academy of Medical Sciences Brain 
Science, Addiction and Drugs (A MS, 
20 0 8).
2. British Medical Association Boosting Your 
Brain Power: Ethical Aspects of Cognitive 
Enhancements (BM A , 20 07). 
3. Foresight Drugs Futures 2025? (UK 
Department of Trade and Industry, 
20 05).
Much ado about 
cognitive 
enhancement
SIR — Henry Greely and 
colleagues call for answers to 
several controversial questions 
regarding the use of drugs by 
healthy people to boost cognitive 
performance. The most important 
scientific and ethical concern they 
raise is safety, not least because 
the pressure that leads people to 
enhance their performance might 
also be a crucial trigger to mental 
disorder. This is particularly 
likely when combined with sleep 
deprivation and anxiety caused 
by aggressive competition, 
as we have already learned 
from the indiscriminate use of 
amphetamines.
However, it would not be 
surprising if the repurposing 
of these drugs has less of 
an impact than expected by 
some and feared by others. 
Myriad personality traits are 
just as important as memory 
or ‘intelligence’ in the overall 
scheme of a successful life. 
Studies of gifted or ‘savant’ 
children show that self-
confidence, discipline, focus, 
drive, resilience and social skills 
are highly complex personality 
traits, often found in successful 
people (see, for example, 
E. W inner Gifted Children: Myths 
and Realities; Basic Books, 1996).
Using medications to improve 
cognitive performance might be 
relevant in the short term. But a 
fully successful future will always 
depend on two very singular 
human features: eagerness to 
excel and setting a high standard 
of achievement.
João Ricardo Oliveira Neuropsychiatry 
Department and Keizo Asami 
Laboratory, Federal University
of Pernambuco, 50670-901, 
Recife-PE, Brazil
A medical view 
of potential 
adverse effects
SIR — Most seasoned physicians 
have had the sobering experience 
of prescribing medications that, 
despite good intentions, caused 
bad outcomes. They would call for 
louder notes of caution than those 
expressed in this Commentary 
when considering the safety of 
‘cognitive-enhancing’ drugs such 
as Ritalin and Adderall. 
The authors do not mention 
the US Food and Drug 
Administration warning on 
the packets of both of these 
drugs. Printed in capitals in a 
black box, it includes phrases 
such as: “amphetamines have 
a high potential for abuse. 
Administration of amphetamines 
for prolonged periods of time 
may lead to drug dependence …
M isuse of amphetamine may 
cause sudden death and serious 
cardiovascular adverse effects.” 
This warning does not cover 
other rare but serious side 
effects, such as Stevens–Johnson 
syndrome (a serious skin 
reaction) or toxic psychosis. 
Furthermore, the incidence of 
serious cardiac arrhythmias is 
likely to be higher in older people 
with incipient cardiovascular 
disease — likely consumers of 
‘healthy’ enhancement. 
Further reason for caution in 
advocating neuroenhancers is the 
disproportionate advantage the 
These letters respond to the Commentary ‘Towards responsible use of cognitive-enhancing drugs by the 
healthy’ by Henry Greely and colleagues (Nature 456, 702–705; 20 08).
532
N ATURE|Vol 457|29 January 20 09OPINION
CORRESPO N DEN CE
Early scientific visitors found mammalian 
fossils awaiting discovery in apothecary shops 
Xu Xing on the discovery of the Peking Man fossils, page 538 
drugs, if effective, would confer 
on the wealthy. The authors’ 
acknowledgment of existing 
disturbing inequities does not 
mean that we should add more. 
A responsible position would 
be to call for a moratorium 
on the use of enhancers until 
enforceable policies to minimize 
socioeconomic disparities are 
in place, research into the use 
and impact of these drugs is 
completed, information on 
risks and benefits is broadly 
disseminated — and physicians, 
educators and regulators have 
articulated professional normative 
positions. 
Anjan Chatterjee Department 
of Neurology and Center for 
Cognitive Neuroscience, University 
of Pennsylvania, Philadelphia, 
Pennsylvania 19104, USA
e-mail: anjan@mail.med.upenn.edu 
Recall of learned 
information may rely 
on taking drug again 
SIR — Henry Greely and 
colleagues identify critical 
areas of public discussion about 
perceptions and use of drugs that 
are alleged or expected to improve 
cognition. 
Stimulants and other drugs 
proposed as potential cognitive 
enhancers are known to create 
profound state dependence, a 
phenomenon in which information 
or associations learned while 
‘under the influence’ of a drug will 
later be remembered or used only 
when the learner has again taken 
the drug. Thus, individuals who 
use amphetamines to improve 
their learning of new information 
may indeed learn slightly faster 
or with less effort than those 
who do not use such drugs. Later, 
however, they may not remember 
or use the learned information 
unless they take amphetamines or 
related drugs again. 
How and when state 
dependence occurs has been 
studied extensively in humans and 
other animals, in well-controlled 
learning tasks in laboratory 
settings. State dependency 
of cognitive enhancers would 
dramatically influence drug use, 
the permanence of learning and 
the ability to use information in 
new conditions. Indeed, state 
dependence can complicate 
clinical use of pharmacotherapies 
for such disorders as anxiety and 
attention-deficit hyperactivity 
disorder.
Greely and colleagues note 
critical research and policy 
questions that societies must 
consider to shape expectations 
about putative cognitive 
enhancers. We urge that the 
discussion includes the known 
and profound state-dependent 
effects of these agents.
Alice M. Young Department of 
Pharmacology and Neuroscience, 
Texas Tech University Health Sciences 
Center, 3601 4th Street, STOP 6592, 
Lubbock, Texas 79430, USA
e-mail: alice.young@ttuhsc.edu 
Francis C. Colpaert Institut de 
Recherche Pierre Fabre, 3, rue des 
Satellites, BP 94244, 31432 Toulouse 
Cedex 4, France
 
Patterns of drug 
use have varied 
throughout history
SIR — Current issues are 
assessed by Henry Greely 
and colleagues, but their 
Commentary contains a bias 
consistent with current Western 
culture. The use of these drugs 
is probably older than recorded 
history. They have often been 
used regardless of social 
convention or rules — and have 
had impacts on societies. 
In the 196 0s, ‘mind-altering 
drugs’ had a different connotation 
from the present, exemplified by 
Timothy Leary’s “Turn on, tune 
in and drop out” philosophy. 
Drugs such as marijuana and LSD 
were said to enhance individual 
thinking and creativity, but 
research both on the mental 
effects of these drugs and on 
their use has decreased. Since 
then, the use of mind-altering 
drugs has shifted towards 
enhancing performance, usually 
with amphetamine analogues. It 
seems that these are becoming 
acceptable when used for the 
goal of efficient production in 
standardized ways.
Don Burnap 11 Oakland Street, Rapid 
City, South Dakota 57701, USA 
The five preceding letters are a 
selection of many comments on this 
Commentary that were submitted 
to Correspondence. Many other 
reactions from readers have 
been posted in a long and lively 
online discussion forum at Nature 
Network, including the following 
anonymous contributions.
Careful use helps me 
do better research, 
and society benefits
SIR — I commend the authors 
of this Commentary on what I 
think is a fair and insightful piece. 
I suspect many of the negative 
commenters are guilty of default 
outrage without careful thought.
I find that my own occasional, 
metered use of these drugs can 
make astounding increases in my 
ability as a researcher — which 
results in tangible benefit to 
society. It’s not a competition, 
I’m not taking an exam. I’m doing 
research; research that I hope 
may one day improve the lives of 
many. I exercise, sleep, eat well 
and I drink coffee. Yet sometimes 
that significant extra boost allows 
me to spend 12 hours successfully 
working through mathematics 
that for weeks I was previously 
unequal to solving. W hy is this the 
act of a social criminal?
Current attitudes towards such 
drugs seem to be that they are 
good if you need them to become 
equal, but wrong if you want to 
become more than equal. Can 
we really be so quick to condemn 
a striving to better ourselves? 
Should we tell brighter students 
to hold back to the median? I 
think not. This issue is not black 
and white; it requires the careful 
grey-scale considerations 
the Commentary authors 
recommend.
It is true that many physicians 
and biomedical researchers have 
placed themselves in quite a 
tangled conflict-of-interest web, 
and that this compromise can be 
dangerous. 
Some of the authors of this 
Commentary may have some 
conflict of interest, which 
thankfully Nature requires 
authors to disclose. However, 
that possible conflict of interest 
does not release you, the reader, 
from your obligation to rationally 
and carefully consider their 
argument. They are not wrong just 
because some of them consult for 
pharmaceutical companies. 
Enhancement means 
a broader role for 
physicians
SIR — This Commentary raises 
a wider issue of perceived 
responsibility. The traditional 
role of physician as healer does 
not sit with the category of 
enhancement. Plastic surgery 
serves as a good analogy here, 
with views remaining varied 
on the ultimate responsibility. 
But with planned, novel, 
pharmacological intervention, 
physicians must surely be party to 
the cause, and thus a broadening 
of their role would be necessary.
Ultimately, the call for 
risk–benefit research and a fuller 
understanding of mechanisms 
is therefore welcome, but the 
real beneficiaries, at least in 
the short term, are likely to be 
dominated by the genuinely needy 
— neurological and psychiatric 
patients. These groups have 
had their needs for cognitive 
enhancement unmet for far 
too long.
Further discussion of the 
Commentary and these 
Correspondence contributions 
is welcome at Nature Network. 
Please visit http: // tinyurl.
com /6nyu29 to have your say.
533
N ATURE|Vol 457|29 January 20 09 OPINION
29.1 Correspondence.indd NS Colin.indd   533 26/1/09   17:29:28


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Correspondence: A Medical View of Potential Adverse Effects

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