Sunday, December 28, 2008

The Cognitive Enhancing Drug Debate

A friend drew my attention to these two articles. I think they are interesting enough to re-post.
Towards responsible use of cognitive-enhancing drugs by the healthy
Henry Greely, Barbara Sahakian, John Harris, Ronald C. Kessler, Michael Gazzaniga, Philip Campbell & Martha J. Farah

Society must respond to the growing demand for cognitive enhancement. That response must start by rejecting the idea that 'enhancement' is a dirty word, argue Henry Greely and colleagues.

Today, on university campuses around the world, students are striking deals to buy and sell prescription drugs such as Adderall and Ritalin — not to get high, but to get higher grades, to provide an edge over their fellow students or to increase in some measurable way their capacity for learning. These transactions are crimes in the United States, punishable by prison.

Many people see such penalties as appropriate, and consider the use of such drugs to be cheating, unnatural or dangerous. Yet one survey estimated that almost 7% of students in US universities have used prescription stimulants in this way, and that on some campuses, up to 25% of students had used them in the past year. These students are early adopters of a trend that is likely to grow, and indications suggest that they're not alone.

In this article, we propose actions that will help society accept the benefits of enhancement, given appropriate research and evolved regulation. Prescription drugs are regulated as such not for their enhancing properties but primarily for considerations of safety and potential abuse. Still, cognitive enhancement has much to offer individuals and society, and a proper societal response will involve making enhancements available while managing their risks.

Paths to enhancement

Many of the medications used to treat psychiatric and neurological conditions also improve the performance of the healthy. The drugs most commonly used for cognitive enhancement at present are stimulants, namely Ritalin (methyphenidate) and Adderall (mixed amphetamine salts), and are prescribed mainly for the treatment of attention deficit hyperactivity disorder (ADHD). Because of their effects on the catecholamine system, these drugs increase executive functions in patients and most healthy normal people, improving their abilities to focus their attention, manipulate information in working memory and flexibly control their responses3. These drugs are widely used therapeutically. With rates of ADHD in the range of 4–7% among US college students using DSM criteria4, and stimulant medication the standard therapy, there are plenty of these drugs on campus to divert to enhancement use.

A newer drug, modafinil (Provigil), has also shown enhancement potential. Modafinil is approved for the treatment of fatigue caused by narcolepsy, sleep apnoea and shift-work sleep disorder. It is currently prescribed off label for a wide range of neuropsychiatric and other medical conditions involving fatigue as well as for healthy people who need to stay alert and awake when sleep deprived, such as physicians on night call. In addition, laboratory studies have shown that modafinil enhances aspects of executive function in rested healthy adults, particularly inhibitory control. Unlike Adderall and Ritalin, however, modafinil prescriptions are not common, and the drug is consequently rare on the college black market. But anecdotal evidence and a readers' survey both suggest that adults sometimes obtain modafinil from their physicians or online for enhancement purposes.

A modest degree of memory enhancement is possible with the ADHD medications just mentioned as well as with medications developed for the treatment of Alzheimer's disease such as Aricept (donepezil), which raise levels of acetylcholine in the brain. Several other compounds with different pharmacological actions are in early clinical trials, having shown positive effects on memory in healthy research subjects. It is too early to know whether any of these new drugs will be proven safe and effective, but if one is it will surely be sought by healthy middle-aged and elderly people contending with normal age-related memory decline, as well as by people of all ages preparing for academic or licensure examinations.

Favouring innovation

Human ingenuity has given us means of enhancing our brains through inventions such as written language, printing and the Internet. Most authors of this Commentary are teachers and strive to enhance the minds of their students, both by adding substantive information and by showing them new and better ways to process that information. And we are all aware of the abilities to enhance our brains with adequate exercise, nutrition and sleep. The drugs just reviewed, along with newer technologies such as brain stimulation and prosthetic brain chips, should be viewed in the same general category as education, good health habits, and information technology — ways that our uniquely innovative species tries to improve itself.

Of course, no two enhancements are equivalent in every way, and some of the differences have moral relevance. For example, the benefits of education require some effort at self-improvement whereas the benefits of sleep do not. Enhancing by nutrition involves changing what we ingest and is therefore invasive in a way that reading is not. The opportunity to benefit from Internet access is less equitably distributed than the opportunity to benefit from exercise. Cognitive-enhancing drugs require relatively little effort, are invasive and for the time being are not equitably distributed, but none of these provides reasonable grounds for prohibition. Drugs may seem distinctive among enhancements in that they bring about their effects by altering brain function, but in reality so does any intervention that enhances cognition. Recent research has identified beneficial neural changes engendered by exercise, nutrition and sleep, as well as instruction and reading. In short, cognitive-enhancing drugs seem morally equivalent to other, more familiar, enhancements.

Many people have doubts about the moral status of enhancement drugs for reasons ranging from the pragmatic to the philosophical, including concerns about short-circuiting personal agency and undermining the value of human effort. Kass, for example, has written of the subtle but, in his view, important differences between human enhancement through biotechnology and through more traditional means. Such arguments have been persuasively rejected. Three arguments against the use of cognitive enhancement by the healthy quickly bubble to the surface in most discussions: that it is cheating, that it is unnatural and that it amounts to drug abuse.

In the context of sports, pharmacological performance enhancement is indeed cheating. But, of course, it is cheating because it is against the rules. Any good set of rules would need to distinguish today's allowed cognitive enhancements, from private tutors to double espressos, from the newer methods, if they are to be banned.

As for an appeal to the 'natural', the lives of almost all living humans are deeply unnatural; our homes, our clothes and our food — to say nothing of the medical care we enjoy — bear little relation to our species' 'natural' state. Given the many cognitive-enhancing tools we accept already, from writing to laptop computers, why draw the line here and say, thus far but no further?

As for enhancers' status as drugs, drug abuse is a major social ill, and both medicinal and recreational drugs are regulated because of possible harms to the individual and society. But drugs are regulated on a scale that subjectively judges the potential for harm from the very dangerous (heroin) to the relatively harmless (caffeine). Given such regulation, the mere fact that cognitive enhancers are drugs is no reason to outlaw them.

Based on our considerations, we call for a presumption that mentally competent adults should be able to engage in cognitive enhancement using drugs.

Substantive concerns and policy goals

All technologies have risks as well as benefits. Although we reject the arguments against enhancement just reviewed, we recognize at least three substantive ethical concerns.

The first concern is safety. Cognitive enhancements affect the most complex and important human organ, and the risk of unintended side effects is therefore both high and consequential. Although regulations governing medicinal drugs ensure that they are safe and effective for their therapeutic indications, there is no equivalent vetting for unregulated 'off label' uses, including enhancement uses. Furthermore, acceptable safety in this context depends on the potential benefit. For example, a drug that restored good cognitive functioning to people with severe dementia but caused serious adverse medical events might be deemed safe enough to prescribe, but these risks would be unacceptable for healthy individuals seeking enhancement.

Enhancement in children raises additional issues related to the long-term effects on the developing brain. Moreover, the possibility of raising cognitive abilities beyond their species-typical upper bound may engender new classes of side effects. Persistence of unwanted recollections, for example, has clearly negative effects on the psyche.

An evidence-based approach is required to evaluate the risks and benefits of cognitive enhancement. At a minimum, an adequate policy should include mechanisms for the assessment of both risks and benefits for enhancement uses of drugs and devices, with special attention to long-term effects on development and to the possibility of new types of side effects unique to enhancement. But such considerations should not lead to an insistence on higher thresholds than those applied to medications.

We call for an evidence-based approach to the evaluation of the risks and benefits of cognitive enhancement.

The second concern is freedom, specifically freedom from coercion to enhance. Forcible medication is generally reserved for rare cases in which individuals are deemed threats to themselves or others. In contrast, cognitive enhancement in the form of education is required for almost all children at some substantial cost to their liberty, and employers are generally free to require employees to have certain educational credentials or to obtain them. Should schools and employers be allowed to require pharmaceutical enhancement as well? And if we answer 'no' to this question, could coercion occur indirectly, by the need to compete with enhanced classmates and colleagues?

Questions of coercion and autonomy are particularly acute for military personnel and for children. Soldiers in the United States and elsewhere have long been offered stimulant medications including amphetamine and modafinil to enhance alertness, and in the United States are legally required to take medications if ordered to for the sake of their military performance. For similar reasons, namely the safety of the individual in question and others who depend on that individual in dangerous situations, one could imagine other occupations for which enhancement might be justifiably required. A hypothetical example is an extremely safe drug that enabled surgeons to save more patients. Would it be wrong to require this drug for risky operations?

Appropriate policy should prohibit coercion except in specific circumstances for specific occupations, justified by substantial gains in safety. It should also discourage indirect coercion. Employers, schools or governments should not generally require the use of cognitive enhancements. If particular enhancements are shown to be sufficiently safe and effective, this position might be revisited for those interventions.

Children once again represent a special case as they cannot make their own decisions. Comparisons between estimates of ADHD prevalence and prescription numbers have led some to suspect that children in certain school districts are taking enhancing drugs at the behest of achievement-oriented parents, or teachers seeking more orderly classrooms. Governments may be willing to let competent adults take certain risks for the sake of enhancement while restricting the ability to take such risky decisions on behalf of children.

The third concern is fairness. Consider an examination that only a certain percentage can pass. It would seem unfair to allow some, but not all, students to use cognitive enhancements, akin to allowing some students taking a maths test to use a calculator while others must go without. (Mitigating such unfairness may raise issues of indirect coercion, as discussed above.) Of course, in some ways, this kind of unfairness already exists. Differences in education, including private tutoring, preparatory courses and other enriching experiences give some students an advantage over others.

Whether the cognitive enhancement is substantially unfair may depend on its availability, and on the nature of its effects. Does it actually improve learning or does it just temporarily boost exam performance? In the latter case it would prevent a valid measure of the competency of the examinee and would therefore be unfair. But if it were to enhance long-term learning, we may be more willing to accept enhancement. After all, unlike athletic competitions, in many cases cognitive enhancements are not zero-sum games. Cognitive enhancement, unlike enhancement for sports competitions, could lead to substantive improvements in the world.

Fairness in cognitive enhancements has a dimension beyond the individual. If cognitive enhancements are costly, they may become the province of the rich, adding to the educational advantages they already enjoy. One could mitigate this inequity by giving every exam-taker free access to cognitive enhancements, as some schools provide computers during exam week to all students. This would help level the playing field.

Policy governing the use of cognitive enhancement in competitive situations should avoid exacerbating socioeconomic inequalities, and should take into account the validity of enhanced test performance. In developing policy for this purpose, problems of enforcement must also be considered. In spite of stringent regulation, athletes continue to use, and be caught using, banned performance-enhancing drugs.

We call for enforceable policies concerning the use of cognitive-enhancing drugs to support fairness, protect individuals from coercion and minimize enhancement-related socioeconomic disparities.

Maximum benefit, minimum harm

The new methods of cognitive enhancement are 'disruptive technologies' that could have a profound effect on human life in the twenty-first century. A laissez-faire approach to these methods will leave us at the mercy of powerful market forces that are bound to be unleashed by the promise of increased productivity and competitive advantage. The concerns about safety, freedom and fairness, just reviewed, may well seem less important than the attractions of enhancement, for sellers and users alike.

Motivated by some of the same considerations, Fukuyama has proposed the formation of new laws and regulatory structures to protect against the harms of unrestrained biotechnological enhancement. In contrast, we suggest a policy that is neither laissez-faire nor primarily legislative. We propose to use a variety of scientific, professional, educational and social resources, in addition to legislation, to shape a rational, evidence-based policy informed by a wide array of relevant experts and stake-holders. Specifically, we propose four types of policy mechanism.

The first mechanism is an accelerated programme of research to build a knowledge base concerning the usage, benefits and associated risks of cognitive enhancements. Good policy is based on good information, and there is currently much we do not know about the short- and long-term benefits and risks of the cognitive-enhancement drugs currently being used, and about who is using them and why. For example, what are the patterns of use outside of the United States and outside of college communities? What are the risks of dependence when used for cognitive enhancement? What special risks arise with the enhancement of children's cognition? How big are the effects of currently available enhancers? Do they change 'cognitive style', as well as increasing how quickly and accurately we think? And given that most research so far has focused on simple laboratory tasks, how do they affect cognition in the real world? Do they increase the total knowledge and understanding that students take with them from a course? How do they affect various aspects of occupational performance?

We call for a programme of research into the use and impacts of cognitive-enhancing drugs by healthy individuals.

The second mechanism is the participation of relevant professional organizations in formulating guidelines for their members in relation to cognitive enhancement. Many different professions have a role in dispensing, using or working with people who use cognitive enhancers. By creating policy at the level of professional societies, it will be informed by the expertise of these professionals, and their commitment to the goals of their profession.

One group to which this recommendation applies is physicians, particularly in primary care, paediatrics and psychiatry, who are most likely to be asked for cognitive enhancers. These physicians are sometimes asked to prescribe for enhancement by patients who exaggerate or fabricate symptoms of ADHD, but they also receive frank requests, as when a patient says "I know I don't meet diagnostic criteria for ADHD, but I sometimes have trouble concentrating and staying organized, and it would help me to have some Ritalin on hand for days when I really need to be on top of things at work." Physicians who view medicine as devoted to healing will view such prescribing as inappropriate, whereas those who view medicine more broadly as helping patients live better or achieve their goals would be open to considering such a request. There is certainly a precedent for this broader view in certain branches of medicine, including plastic surgery, dermatology, sports medicine and fertility medicine.

Because physicians are the gatekeepers to medications discussed here, society looks to them for guidance on the use of these medications and devices, and guidelines from other professional groups will need to take into account the gatekeepers' policies. For this reason, the responsibilities that physicians bear for the consequences of their decisions are particularly sensitive, being effectively decisions for all of us. It would therefore be helpful if physicians as a profession gave serious consideration to the ethics of appropriate prescribing of cognitive enhancers, and consulted widely as to how to strike the balance of limits for patient benefit and protection in a liberal democracy. Examples of such limits in other areas of enhancement medicine include the psychological screening of candidates for cosmetic surgery or tubal ligation, and upper bounds on maternal age or number of embryos transferred in fertility treatments. These examples of limits may not be specified by law, but rather by professional standards.

Other professional groups to which this recommendation applies include educators and human-resource professionals. In different ways, each of these professions has responsibility for fostering and evaluating cognitive performance and for advising individuals who are seeking to improve their performance, and some responsibility also for protecting the interests of those in their charge. In contrast to physicians, these professionals have direct conflicts of interest that must be addressed in whatever guidelines they recommend: liberal use of cognitive enhancers would be expected to encourage classroom order and raise standardized measures of student achievement, both of which are in the interests of schools; it would also be expected to promote workplace productivity, which is in the interests of employers.

Educators, academic admissions officers and credentials evaluators are normally responsible for ensuring the validity and integrity of their examinations, and should be tasked with formulating policies concerning enhancement by test-takers. Laws pertaining to testing accommodations for people with disabilities provide a starting point for discussion of some of the key issues, such as how and when enhancements undermine the validity of a test result and the conditions under which enhancement should be disclosed by a test-taker.

The labour and professional organizations of individuals who are candidates for on-the-job cognitive enhancement make up our final category of organization that should formulate enhancement policy. From assembly line workers to surgeons, many different kinds of employee may benefit from enhancement and want access to it, yet they may also need protection from the pressure to enhance.

We call for physicians, educators, regulators and others to collaborate in developing policies that address the use of cognitive-enhancing drugs by healthy individuals.

The third mechanism is education to increase public understanding of cognitive enhancement. This would be provided by physicians, teachers, college health centres and employers, similar to the way that information about nutrition, recreational drugs and other public-health information is now disseminated. Ideally it would also involve discussions of different ways of enhancing cognition, including through adequate sleep, exercise and education, and an examination of the social values and pressures that make cognitive enhancement so attractive and even, seemingly, necessary.

We call for information to be broadly disseminated concerning the risks, benefits and alternatives to pharmaceutical cognitive enhancement.

The fourth mechanism is legislative. Fundamentally new laws or regulatory agencies are not needed. Instead, existing law should be brought into line with emerging social norms and information about safety. Drug law is one of the most controversial areas of law, and it would be naive to expect rapid or revolutionary change in the laws governing the use of controlled substances. Nevertheless, these laws should be adjusted to avoid making felons out of those who seek to use safe cognitive enhancements. And regulatory agencies should allow pharmaceutical companies to market cognitive-enhancing drugs to healthy adults provided they have supplied the necessary regulatory data for safety and efficacy.

We call for careful and limited legislative action to channel cognitive-enhancement technologies into useful paths.


Like all new technologies, cognitive enhancement can be used well or poorly. We should welcome new methods of improving our brain function. In a world in which human workspans and lifespans are increasing, cognitive enhancement tools — including the pharmacological — will be increasingly useful for improved quality of life and extended work productivity, as well as to stave off normal and pathological age-related cognitive declines. Safe and effective cognitive enhancers will benefit both the individual and society.

But it would also be foolish to ignore problems that such use of drugs could create or exacerbate. With this, as with other technologies, we need to think and work hard to maximize its benefits and minimize its harms.

Join the debate on this topic at Nature Network (access to full article requires subscription)

And a New York Times op-ed responding to the above article:
Living the Off-Label Life

Published: December 26, 2008

What if you could just take a pill and all of a sudden remember to pay your bills on time? What if, thanks to modern neuroscience, you could, simultaneously, make New Year’s Eve plans, pay the mortgage, call the pediatrician, consolidate credit card debt and do your job — well — without forgetting dentist appointments or neglecting to pick up your children at school?

Would you do it? Tune out the distractions of our online, on-call, too-fast A.D.D.-ogenic world with focus and memory-enhancing medications like Ritalin or Adderall? Stay sharp as a knife — no matter how overworked and sleep-deprived — with a mental-alertness-boosting drug like the anti-narcolepsy medication Provigil?

I’ve always said no. Fantasy aside, I’ve always rejected the idea of using drugs meant for people with real neurological disorders to treat the pathologies of everyday life.

Most of us, viscerally, do. Cognitive enhancement — a practice typified by the widely reported abuse of psychostimulants by college students cramming for exams, and by the less reported but apparently growing use of mind-boosters like Provigil among in-the-know scientists and professors — goes against the grain of some of our most basic beliefs about fairness and meritocracy. It seems to many people to be unnatural, inhuman, hubristic, pure cheating.

That’s why when Henry Greely, director of Stanford Law School’s Center for Law and the Biosciences, published an article, with a host of co-authors, in the science journal Nature earlier this month suggesting that we ought to rethink our gut reactions and “accept the benefits of enhancement,” he was deluged with irate responses from readers.

“There were three kinds of e-mail reactions,” he told me in a phone interview last week. “‘How much crack are you smoking? How much money did your friends in pharma give you? How much crack did you get from your friends in pharma?’ ”

As Americans, our default setting on matters of psychotropic drugs — particularly when it comes to medicating those who are not very ill — tends to be, as the psychiatrist Gerald Klerman called it in 1972, something akin to “pharmacological Calvinism.” People should suffer and endure, the thinking goes, accept what hard work and their God-given abilities bring them and hope for no more.

But Greely and his Nature co-authors suggest that such arguments are outdated and intellectually dishonest. We enhance our brain function all the time, they say — by drinking coffee, by eating nutritious food, by getting an education, even by getting a good night’s sleep. Taking brain-enhancing drugs should be viewed as just another step along that continuum, one that’s “morally equivalent” to such “other, more familiar, enhancements,” they write.

Normal life, unlike sports competitions, they argue, isn’t a zero-sum game, where one person’s doped advantage necessarily brings another’s disadvantage. A surgeon whose mind is extra-sharp, a pilot who’s extra alert, a medical researcher whose memory is fine-tuned to make extraordinary connections, is able to work not just to his or her own benefit, but for that of countless numbers of people. “Cognitive enhancement,” they write, “unlike enhancement for sports competitions, could lead to substantive improvements in the world.”

I’m not convinced of that. I’m not sure that pushing for your personal best — all the time — is tantamount to truly being the best person you can be. I have long thought that a life so frenetic and fractured that it drives “neuro-normal” people to distraction, leaving them sleep-deprived and exhausted, demands — indeed, screams for — systemic change.

But now I do wonder: What if the excessive demands of life today are creating ever-larger categories of people who can’t reach their potential due to handicaps that in an easier time were just quirks? (Absent-minded professor-types were, for generations, typically men who didn’t need to be present — organized and on-time — for their kids.) Is it any fairer to saddle a child with a chronically overwhelmed parent than with one suffering from untreated depression?

And, furthermore, how much can most of us, on a truly meaningful scale, change our lives? At a time of widespread layoffs and job anxiety among those still employed, can anyone but the most fortunate afford to cut their hours to give themselves time to breathe? Can working parents really sacrifice on either side of the wage-earning/life-making equation? It’s disturbing to think that we just have to make do with the world we now live in. But to do otherwise is for most people an impossible luxury.

For some of us, saddled with brains ill-adapted to this era, and taxed with way too many demands and distractions, pharmacological Calvinism may now be a luxury, too.

My opinion may follow.

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