Source: Observer
Date: 20 September 2009

Can a daily pill really boost your brain power?

In America, university students are taking illegally obtained prescription drugs to make
them more intelligent. But would you pop a smart pill to improve your performance?

Margaret Talbot investigates the brave new world of neuro enhancement

A young man I'll call Alex recently graduated from Harvard. As a history major, Alex wrote about a dozen papers a term. He also ran a student organisation, for which he often worked more than 40 hours a week; when he wasn't working, he had classes. Weeknights were devoted to all the schoolwork he couldn't finish during the day, and weekend nights were spent drinking with friends and going to parties. "Trite as it sounds," he told me, it seemed important to "maybe appreciate my own youth". Since, in essence, this life was impossible, Alex began taking Adderall to make it possible.

Adderall, a stimulant composed of mixed amphetamine salts, is commonly prescribed for children and adults who have been given a diagnosis of attention-deficit hyperactivity disorder (ADHD). But in recent years Adderall and Ritalin, another stimulant, have been adopted as cognitive enhancers: drugs that high-functioning, overcommitted people take to become higher-functioning and more overcommitted. (Such use is "off label", meaning that it does not have the approval of either the drug's manufacturer or the FDA, America's Food and Drug Administration.) College campuses have become laboratories for experimentation with neuroenhancement, and Alex was an ingenious experimenter. His brother had received a diagnosis of ADHD, and in his first year as an undergraduate Alex obtained an Adderall prescription for himself by describing to a doctor symptoms that he knew were typical of the disorder. During his college years, Alex took 15mg of Adderall most evenings, usually after dinner, guaranteeing that he would maintain intense focus while losing "any ability to sleep for approximately eight to 10 hours". In his second year, he persuaded the doctor to add a 30mg "extended-release" capsule to his daily regime.

Alex recalled one week during his junior year when he had four term papers due. Minutes after waking on Monday, around 7.30am, he swallowed some "immediate-release" Adderall. The drug, along with a steady stream of caffeine, helped him to concentrate during classes and meetings, but he noticed some odd effects; at a morning tutorial, he explained to me in an email, "I alternated between speaking too quickly and thoroughly on some subjects and feeling awkwardly quiet during other points of the discussion." Lunch was a blur: "It's always hard to eat much when on Adderall." That afternoon he went to the library, where he spent "too much time researching a paper rather than actually writing it - a problem that is common to all intellectually curious students on stimulants". At eight he attended a two-hour meeting "with a group focused on student mental health issues". Alex then "took an extended-release Adderall" and worked productively on the paper all night. At eight the next morning he attended a meeting of his student organisation; he felt like "a zombie" and went back to his room. He fell asleep until noon, waking "in time to polish my first paper and hand it in".

I met Alex one evening last summer, at an appealingly scruffy bar in the New England city where he lives. Skinny and bearded, and wearing faded hipster jeans, he looked like the lead singer in an indie band. He was ingratiating and articulate, and smoked cigarettes with an ironic air of defiance. Alex was happy enough to talk about his frequent use of Adderall at Harvard, but he didn't want to see his name in print; he's involved with an internet start-up and worried that potential investors might disapprove of his habit.

After we had ordered beers he said: "One of the most impressive features of being a student is how aware you are of a 24-hour work cycle. When you conceive of what you have to do for school, it's not in terms of nine to five but in terms of what you can physically do in a week while still achieving a variety of goals - social, romantic, extracurricular, CV-building, academic."

Alex was eager to dispel the notion that students who took Adderall were "academic automatons who are using it in order to be first in their class". In fact, he said, "it's often people" - mainly guys - "who are looking in some way to compensate for activities that are detrimental to their performance". He explained, "At Harvard, at the most basic level, they aim to do better than they would have otherwise. Everyone is aware that if you were up at 3am writing this paper it isn't going to be as good as it could have been. The fact that you were partying all weekend, or spent the last week being high, watching Lost - that's going to take a toll."

Alex's sense of who uses stimulants for so-called "non-medical" purposes is borne out by two dozen or so scientific studies. In 2005 a team led by Sean Esteban McCabe, a professor at the University of Michigan, reported that in the previous year 4.1% of American undergraduates had taken prescription stimulants for off-label use - at one school the figure was 25%, while a 2002 study at a small college found that more than 35% of the students had used prescription stimulants non-medically in the previous year.

Drugs such as Adderall can cause nervousness, headaches, sleeplessness and decreased appetite, among other side-effects. An FDA warning on Adderall's label notes that "amphetamines have a high potential for abuse" and can lead to dependence. (The label also mentions that adults using Adderall have reported serious cardiac problems, though the role of the drug in those cases is unknown.) Yet college students tend to consider Adderall and Ritalin as benign, in part because they are likely to know peers who have taken the drugs since childhood for ADHD. Indeed, McCabe reports, most students who use stimulants for cognitive enhancement obtain them from an acquaintance with a prescription. Usually the pills are given away, but some students sell them.

According to McCabe's research team, white male undergraduates at highly competitive schools are the most frequent student users of neuroenhancers. Users are also more likely to belong to a fraternity or a sorority, and to have a grade point average (GPA) of 3.0 - ie satisfactory - or lower. They are 10 times as likely to report that they have smoked marijuana in the past year and 20 times as likely to say that they have used cocaine. In other words, they are decent students at schools where to be a great student you have to give up a lot more partying than they're willing to give up.

The BoredAt websites - which allow college students to chat idly while they're ostensibly studying - are filled with messages about Adderall. Posts like these, from the BoredAtPenn site, are typical: "I have some Adderall - I'm sitting by room 101.10 in a grey shirt and headphones"; "I have Adderall for sale 20mg for $15"; "I took Adderall at 8pm, it's 6:30am and I've barely blinked." On the Columbia site one poster complains that her friends take Adderall "like candy", adding: "I don't want to be at a disadvantage to everyone else. Is it really that dangerous? My grades weren't that great this year and I could do with a bump." A Columbia student responds: "It's probably not a good idea if you're not prescribed", but offers practical advice anyway: "Keep the dose normal and don't grind them up or snort them." Occasional dissenters ("I think there should be random drug testing at every exam") are drowned out by testimonials like this one, from the BoredAtHarvard site: "I don't want to be a pusher or start people on something bad, but Adderall is amazing."

Alex remains enthusiastic about Adderall, but he also has a slightly jaundiced critique of it. "It only works as a cognitive enhancer insofar as you are dedicated to accomplishing the task at hand," he said. "The number of times I've taken Adderall late at night and decided that, rather than starting my paper, hey, I'll organise my entire music library! I've seen people obsessively cleaning their rooms on it." Alex thought that generally the drug helped him to bear down on his work, but it also tended to produce writing with a characteristic flaw. "Often I've looked back at papers I've written on Adderall, and they're verbose. They're labouring a point, trying to create this airtight argument. I'd produce two pages on something that could be said in a couple of sentences." Nevertheless, his Adderall-assisted papers usually earned him at least a B. They got the job done. As Alex put it: "Productivity is a good thing."

Last April the scientific journal Nature published the results of an informal online poll asking whether readers attempted to sharpen "their focus, concentration, or memory" by taking drugs such as Ritalin and Provigil, a newer kind of stimulant, known generically as modafinil, which was developed to treat narcolepsy. One in five respondents said they did. A majority of the 1,400 readers who responded said that healthy adults should be permitted to take brain boosters for non-medical reasons, and 69% said that mild side-effects were an acceptable risk. Though a majority said that such drugs should not be made available to children who had no diagnosed medical condition, a third admitted that they would feel pressure to give "smart drugs" to their kids if they learned that other parents were doing so.

Such competitive anxieties are already being felt in the workplace. Recently an advice column in Wired featured a question from a reader worried about "a rising star at the firm" who was "using unprescribed modafinil to work crazy hours. Our boss has started getting on my case for not being as productive." And on internet forums such as ImmInst (Immortality Institute), whose members share a nerdy passion for tweaking their cognitive function through drugs and supplements, people trade advice about dosages and "stacks" - improvised combinations - of neuroenhancers ("Cut a tablet into fourths and took 25mg every four hours, four times today, and had a great and productive day - with no side-effects"). In one recent post a 52-year-old - who was working full time, studying for an advanced degree at night and "married, etc" - wrote that after experimenting with modafinil he had settled on two daily doses of 100mg each. He believed that he was "performing a little better", adding: "I also feel slightly more animated when in discussion."

Not long ago I met Anjan Chatterjee, a neurologist at the University of Pennsylvania, in his office at the labyrinthine Penn hospital complex. Chatterjee's main research interests are in subjects like the neurological basis of spatial understanding, but in the past few years, as he has heard more about students taking cognitive enhancers, he has begun writing about the ethical implications of such behaviour. In 2004 he coined the term "cosmetic neurology" to describe the practice of using drugs developed for recognised medical conditions to strengthen ordinary cognition. Chatterjee worries about cosmetic neurology, but he thinks that it will eventually become as acceptable as cosmetic surgery; in fact with neuroenhancement it's harder to argue that it's frivolous. As he notes in a 2007 paper: "Many sectors of society have winner-take-all conditions in which small advantages produce disproportionate rewards." At school and at work, the usefulness of being "smarter", needing less sleep and learning more quickly is "abundantly clear". In the near future, he predicts, some neurologists will refashion themselves as "quality-of-life consultants" whose role will be "to provide information while abrogating final responsibility for these decisions to patients". The demand is certainly there: from an ageing population that won't put up with memory loss; from overwrought parents bent on giving their children every possible edge; from anxious employees in an efficiency-obsessed, BlackBerry-equipped office culture where work never really ends.

Chatterjee told me that many people who come to his clinic are cognitively preoccupied versions of what doctors call the "worried well". He had just seen a middle-aged woman, a successful Philadelphia lawyer, who mentioned having to struggle a bit to come up with certain names. "Here's an example of someone who by most measures is doing perfectly fine," Chatterjee said. "She's not having any trouble at work. But she notices she's having some problems, and it's very hard to know how much of that is just getting older." Of course, people in her position could strive to get regular exercise and plenty of intellectual stimulation, both of which have been shown to help maintain cognitive function. But maybe they're already doing so and want a bigger mental rev-up, or maybe they want something easier than sweaty workouts and Russian novels: they want a pill.

Recently I spoke on the phone with Barbara Sahakian, a clinical neuropsychologist at Cambridge University and the co-author of a 2007 article in Nature entitled "Professor's Little Helper". Sahakian, who also consults for several pharmaceutical companies, and her co-author, Sharon Morein-Zamir, reported that a number of their colleagues were using prescription drugs like Adderall and Provigil. Because the drugs are easy to buy online, they wrote, it would be difficult to stop their spread: "The drive for self-enhancement of cognition is likely to be as strong if not stronger than in the realms of 'enhancement' of beauty and sexual function." (In places like Cambridge, at least.)

When I spoke with Sahakian she had just flown from England to Scottsdale, Arizona, to attend a conference, and she was tired. "We may be healthy and high-functioning, and think of ourselves that way," she told me, "but it's very rare that we are actually functioning at our optimal level. Take me. I'm over here and I've got jet lag and I've got to give a talk tonight and perform well in what will be the middle of the night, UK time." She mentioned businessmen who have to fly back and forth across the Atlantic: "The difference between making a deal and not is huge, and they sometimes only have one meeting to try and do it." She added: "We are a society that so wants a quick fix that many people are happy to take drugs."

For the moment, people looking for that particular quick fix have a limited choice of meds. But given the amount of money and research hours being spent on developing drugs to treat cognitive decline, Provigil and Adderall are likely to be joined by a bigger pharmacopoeia. Among the drugs in the pipeline are ampakines, which target a type of glutamate receptor in the brain; it is hoped that they may stem the memory loss associated with diseases like Alzheimer's. But ampakines may also give healthy people a palpable cognitive boost. A 2007 study of 16 healthy elderly volunteers found that 500mg of one particular ampakine "unequivocally" improved short-term memory, though it appeared to detract from episodic memory - the recall of past events. Another class of drugs, cholinesterase inhibitors, which are already being used with some success to treat Alzheimer's patients, have also shown promise as neuroenhancers. In one study the drug donepezil strengthened the performance of pilots on flight simulators; in another, of 30 healthy young male volunteers, it improved verbal and visual episodic memory. Several pharmaceutical companies are working on drugs that target nicotine receptors in the brain in the hope that they can replicate the cognitive uptick that smokers get from cigarettes.

Zack and Casey Lynch are a young couple who, in 2005, launched NeuroInsights, a company that advises investors on developments in brain-science technology. (Since then, they've also founded a lobbying group, the Neurotechnology Industry Organization.) Casey and Zack met as undergraduates at UCLA; she went on to get a master's in neuroscience and he became an executive at a software company. Last summer I had coffee with them in San Francisco and they both spoke with casual certainty about the coming market for neuroenhancers. Zack, whose book, The Neuro Revolution, was published in July, said: "We live in an information society. What's the next form of human society? The neuro-society." In coming years, he said, scientists will understand the brain better, and we'll have improved neuroenhancers that some people will use therapeutically, others because they are "on the borderline of needing them therapeutically" and others purely "for competitive advantage".

Zack explained that he didn't really like the term enhancement: "We're not talking about superhuman intelligence. No one's saying we're coming out with a pill that's going to make you smarter than Einstein! What we're really talking about is enabling people." He sketched a bell curve on the back of a napkin. "Almost every drug in development is something that will take someone who's working at, like, 40% or 50%, and take them up to 80," he said.

New psychiatric drugs have a way of creating markets for themselves. Disorders often become widely diagnosed after drugs come along that can alter a set of suboptimal behaviours. In this way Ritalin and Adderall helped make ADHD a household name, and advertisements for antidepressants have helped define shyness as a malady. If there's a pill that can clear up the wavering focus of sleep-deprived youth or mitigate the tip-of-the-tongue experience of middle age, then those rather ordinary states may come to be seen as syndromes.

As Casey put it: "The drugs get better, and the markets become bigger."

"Yes," Zack said. "We call it the lifestyle-improvement market."

The Lynches said that Provigil was a classic example of a related phenomenon: mission creep. In 1998, Cephalon, the pharmaceutical company that manufactures it, received US government approval to market the drug but only for "excessive daytime sleepiness" due to narcolepsy; by 2004, Cephalon had obtained permission to expand the labelling so that it included sleep apnoea and "shift-work sleep disorder". Net sales of Provigil climbed from $196m in 2002 to $988m in 2008.

Cephalon executives have repeatedly said that they do not condone off-label use of Provigil, but in 2002 the company was reprimanded by the FDA for distributing marketing materials that presented the drug as a remedy for tiredness, "decreased activity" and other supposed ailments. And in 2008 Cephalon paid $425m and pleaded guilty to a federal criminal charge relating to its promotion of off-label uses for Provigil and two other drugs. Later this year, Cephalon plans to introduce Nuvigil, a longer-lasting variant of Provigil. Candace Steele, a spokesperson, said: "We're exploring its possibilities to treat excessive sleepiness associated with schizophrenia, bipolar depression, traumatic injury and jet lag." Though she emphasised that Cephalon was not developing Nuvigil as a neuroenhancer, she noted: "As part of the preparation for some of these diseases, we're looking to see if there's improvement in cognition."

Unlike many hypothetical scenarios that bioethicists worry about - human clones, "designer babies" - cognitive enhancement is already in full swing. But how much do they actually help? Are they potentially harmful or addictive? Then there's the question of what we mean by "smarter". Could enhancing one kind of thinking exact a toll on others? All these questions need proper scientific answers, but for now much of the discussion is taking place furtively, among the increasing number of people who are performing daily experiments on their own brains.

Paul Phillips was unusual for a professional poker player. When he joined the circuit in the late 1990s he was already a millionaire: a twentysomething tech guy who helped found an internet portal called go2net and cashed in at the right moment. He was cerebral and at times brusque. On the international poker scene Phillips cultivated a geeky New Wave style. He wore vintage shirts in wild geometric patterns; his hair was dyed orange or silver one week, shaved off the next. Most unusual of all, Phillips talked freely about taking prescription drugs - Adderall and, especially, Provigil - in order to play better cards.

He first took up the game in 1995, when he was in college. He recalled: "It was very mathematical, but you could also inject yourself into the game and manipulate the other guy with words" - more so than in a game like chess. Phillips soon felt that he had mastered the strategic aspects of poker. The key variable was execution. At tournaments he needed to be able to stay focused for 14 hours at a stretch, often for several days, but he found it difficult to do so. In 2003, a doctor gave him a diagnosis of ADHD and he began taking Adderall. Within six months, he had won $1.6m at poker - far more than he'd won in the previous four years. Adderall not only helped him concentrate, it also helped him resist the impulse to keep playing losing hands out of boredom. In 2004, Phillips asked his doctor to give him a prescription for Provigil, which he added to his Adderall regimen. He took 200-300mg of Provigil a day, which he felt helped him settle into an even more serene and objective state of mindfulness; as he put it, he felt "less like a participant than an observer - and a very effective one". Though Phillips sees neuroenhancers as essentially steroids for the brain, they haven't yet been banned from poker competitions.

Last summer, I visited Phillips in the high desert resort town of Bend, Oregon, where he lives with his wife, Kathleen, and their two daughters, Ivy and Ruby. Phillips, who is now 36, took me for coffee at a cheery café called Thump. Wearing shorts, flip-flops and a black T-shirt, he said: "Poker is about sitting in one place, watching your opponents for a long time, and making better observations about them than they make about you." With Provigil, he "could process all the information about what was going on at the table and do something about it". Though there is no question that Phillips became much more successful at poker after taking neuroenhancers, I asked him if his improvement could be explained by a placebo effect, or by coincidence. He doubted it, but allowed that it could. Still, he said, "there's a sort of clarity I get with Provigil. With Adderall, I'd characterise the effect as correction - correction of an underlying condition. Provigil feels like enhancement." And, whereas Adderall made him "jittery", Provigil's effects were "completely limited to my brain". He had "zero difficulty sleeping".

On the other hand, Phillips said, Provigil's effects "have attenuated over time. The body is an amazing adjusting machine, and there's no upside that I've been able to see to just taking more." A few years ago Phillips tired of poker and started playing competitive Scrabble. He was good, but not that good. He was older than many of his rivals and he needed to undertake a lot of rote memorisation, which didn't come as easily as it once had. "I stopped short of memorising the entire dictionary, and to be really good you have to get up to eight- and nine-letter words," he told me. "But I did learn every word up to five letters, plus maybe 10,000 seven- and eight-letter words." Provigil, he said, helped with the memorisation process but, "it's not going to make you smarter. It's going to make you better able to use the tools you have for a sustained period."

Similarly, a 74-year-old who published a letter in Nature last year offered a charmingly specific description of his modafinil habit: "Previously I could work competently on the fracture-mechanics of high-silica stone (while replicating ancient tool-flaking techniques) for about an hour. With modafinil I could continue for almost three hours."

Cephalon has publicly downplayed the idea that the drug can be used as a smart pill. In 2007, the company's founder and CEO, Frank Baldino Jr, told the trade journal Pharmaceutical Executive: "I think if you're tired, Provigil will keep you awake. If you're not tired, it's not going to do anything."

But Baldino may have been overly modest. In 2002, researchers at Cambridge University gave 60 healthy young male volunteers a battery of standard cognitive tests. One group received modafinil, the other a placebo. The modafinil group performed better on several tasks, such as the "digit span" test, in which subjects are asked to repeat increasingly longer strings of numbers forwards, then backwards. They also did better in recognising repeated visual patterns and at a spatial-planning challenge known as the Tower of London task. (It's not nearly as fun as it sounds.) Writing in the journal Psychopharmacology, the study's authors said the results suggested that "modafinil offers significant potential as a cognitive enhancer".

Phillips told me that, much as he believes in neuroenhancers, he did not want to be "the poster boy for smart-in-a-pill". At one point, he said: "We really don't know the possible implications for long-term use of these things." (He recently stopped taking Provigil every day, replacing it with another prescription stimulant.) Nor does he think we need to be turning up the crank another notch on how hard we work. "But," he said, "the baseline competitive level is going to reorientate around what these drugs make possible, and you can choose to compete or not."

Provigil may well confer a temporary advantage on healthy people, but this doesn't mean that it's ready to replace your morning espresso. Anjan Chatterjee told me that there "just aren't enough studies of these drugs in normal people". One study, published recently in the Journal of the American Medical Association, suggests that Provigil can be habit-forming. A group led by Nora Volkow, the director of the National Institute on Drug Abuse, scanned the brains of 10 men after they had been given a placebo, and also after they had been given a dose of modafinil. The modafinil appeared to lead to an increase in the brain chemical dopamine. "Because drugs that increase dopamine have the potential for abuse," Volkow's report concluded, "these results suggest that risk for addiction in vulnerable persons merits heightened awareness." (Cephalon, in a response to the report, notes that Provigil's label urges physicians to monitor patients closely, especially those with a history of drug abuse.) On the website Erowid, where people vividly and anonymously report their experiences with legal and illegal drugs, some modafinil users have described a dependency on the drug. One man, who identified himself as a former biochemistry student, said that he had succeeded in kicking cocaine and opiate habits but couldn't stop using modafinil. Whenever he ran out of the drug, he said, "I start to freak out." After "four to five days" without it, "the head fog starts to come back".

Eliminating foggy-headedness seems to be the goal of many users of neuroenhancers. But can today's drugs actually accomplish this? I recently posed this question to Chatterjee's colleague Martha Farah, who is a psychologist at Penn and the director of its Center for Cognitive Neuroscience. She is deeply fascinated by, and mildly critical of, neuroenhancers, but basically in favour - with the important caveat that we need to know much more about how these drugs work. While Farah does not take neuroenhancers, she had just finished a paper in which she reviewed the evidence on prescription stimulants as neuroenhancers from 40 laboratory studies involving healthy subjects. Most of the studies looked at one of three types of cognition: learning, working memory, and cognitive control. A typical learning test asks subjects to memorise a list of paired words; an hour, a few days, or a week later, they are presented with the first words in the pairs and asked to come up with the second. Neuroenhancers did improve retention, especially where subjects had been asked to remember information for several days or longer.

Working memory has been likened to a mental scratch pad: you use it to keep relevant data in mind while you're completing a task. (Imagine a cross-examination, in which a lawyer has to keep track of the answers a witness has given and formulate new questions based on them.) In one common test subjects are shown a series of items - usually letters or numbers - and then presented with challenges: was this number or letter in the series? Was this one? In the working-memory tests, subjects performed better on neuroenhancers, though several of the studies suggested that the effect depended on how good a subject's working memory was to begin with: the better it was, the less benefit the drugs provided.

The third category was cognitive control - how effectively you can check yourself in circumstances where the most natural response is the wrong one. A classic test is the Stroop Task, in which people are shown the name of a colour (let's say orange) written in a different colour (let's say purple). They're asked to read the word (which is easy, because our habitual response to a word is to read it) or to name the ink colour (which is harder, because our first impulse is to say "orange"). These studies presented a more mixed picture, but overall they showed some benefit "for most normal healthy subjects" - especially for people who had inherently poorer cognitive control.

Farah told me: "These drugs will definitely help some technically normal people - that is, people who don't meet the diagnostic criteria for ADHD or any kind of cognitive impairment." But, she emphasised, "They will help people in the lower end of the ability range more than in the higher end." One explanation for this phenomenon might be that the more adept you are at a given task, the less room you have to improve. Farah has a hunch that there may be another reason that existing drugs - so far, at least - don't offer as much help to people with greater intellectual abilities. Drugs like Ritalin and Adderall work in part by elevating the amount of dopamine in the brain. Dopamine is something you want just enough of: too little, and you may not be as alert and motivated as you need to be; too much, and you may feel overstimulated. Neuroscientists have discovered that some people have a gene that leads the brain to break down dopamine faster, leaving less of it available; such people are generally a little worse at certain cognitive tasks. People with more available dopamine are generally somewhat better at the same tasks. It makes sense, then, that people with naturally low dopamine would benefit more from an artificial boost.

Of course learning, working memory and cognitive control represent just a few aspects of thinking. Farah concluded that studies looking at other kinds of cognition - verbal fluency, for instance - were too few and too contradictory to tell us much. Both Chatterjee and Farah have wondered whether drugs that heighten users' focus might dampen their creativity. After all, some of our best ideas come to us not when we sit down at a desk but rather when we're in the shower or walking the dog - letting our minds roam. Jimi Hendrix reported that the inspiration for "Purple Haze" came to him in a dream; the chemist Friedrich August Kekule claimed that he discovered the ring structure of benzene during a reverie in which he saw the image of a snake biting its tail. Farah told me: "There is some evidence that suggests that individuals who are better able to focus on one thing and filter out distractions tend to be less creative.

"More and more of our young people are using these drugs to help them work. They've got their laptop, their iPhone, and their Adderall. This rising generation of workers and leaders may have a subtly different style of thinking and working, because they're using these drugs or because they learned to work using these drugs, so that even if you take the drugs away they'll still have a certain approach. I'm a little concerned that we could be raising a generation of very focused accountants."

Farah has also been considering the ethical complications resulting from the rise of smart drugs. Don't neuroenhancers confer yet another advantage on the kind of people who already can afford private tutors? Writing last year in the Cavalier Daily, the student newspaper of the University of Virginia, a columnist named Greg Crapanzano argued that neuroenhancers "create an unfair advantage for the users who are willing to break the law in order to gain an edge. These students create work that is dependent on the use of a pill rather than their own work ethic." Of course, it's hard to imagine a university administration that would require students to pee in a cup before entering an exam hall. And even with the aid of a neuroenhancer, you still have to write the essay, conceive the screenplay or finish the grant proposal. Moreover, if you can take credit for work you've done on caffeine or nicotine, then you can take credit for work produced on Provigil.

Farah questions the idea that neuroenhancers will expand inequality. Citing the "pretty clear trend across the studies that say neuroenhancers will be less helpful for people who score above average", she said that cognitive-enhancing pills could actually become levellers if they are dispensed cheaply. A 2007 discussion paper published by the British Medical Association (BMA) also makes this point: "Selective use of neuroenhancers among those with lower intellectual capacity, or those from deprived backgrounds who do not have the benefit of additional tuition, could enhance the educational opportunities for those groups." If the idea of giving a pill as a substitute for better teaching seems repellent - like substituting an IV drip of synthetic nutrition for actual food - it may be preferable to a scenario in which only wealthy kids receive a frequent mental boost.

Farah was one of several scholars who contributed to a recent article in Nature, "Towards Responsible Use of Cognitive Enhancing Drugs by the Healthy". The optimistic tone of the article suggested that some bioethicists are leaning towards endorsing neuroenhancement. "Like all new technologies, cognitive enhancement can be used well or poorly," the article declared. "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." The BMA report offered a similarly upbeat observation: "Universal access to enhancing interventions would bring up the baseline level of cognitive ability, which is generally seen to be a good thing."

And yet when enthusiasts share their vision of our neuroenhanced future it can sound dystopian. Zack Lynch, of NeuroInsights, gave me a rationale for smart pills that I found particularly grim. "If you're a 55-year-old in Boston, you have to compete with a 26-year-old from Mumbai now, and those kinds of pressures are only going to grow," he began. Countries other than the US might tend to be a little looser with their regulations and offer approval of new cognitive enhancers first. "And if you're a company that's got 47 offices worldwide, and all of a sudden your Singapore office is using cognitive enablers, and you're saying to Congress: 'I'm moving all my financial operations to Singapore and Taiwan, because it's legal to use those there', you bet that Congress is going to say: 'Well, OK.' It will be a moot question then.

It would be like saying: 'No, you can't use a cell phone. It might increase productivity!'" If we eventually decide that neuroenhancers work, and are basically safe, will we one day enforce their use? Lawmakers might compel certain workers - A&E doctors, air-traffic controllers - to take them. (Indeed, the US Air Force already makes modafinil available to pilots embarking on long missions.) For the rest of us, the pressure will be subtler - that queasy feeling I get when I remember that my younger colleague is taking Provigil to meet deadlines. All this may be leading to a kind of society I'm not sure I want to live in: a society where we're even more overworked and driven by technology than we already are, and where we have to take drugs to keep up; a society where we give children academic steroids along with their daily vitamins.

Paul McHugh, a psychiatrist at Johns Hopkins University, has written sceptically about cosmetic neurology. In a 2004 essay he notes that at least once a year in his private practice he sees a young person - usually a boy - whose parents worry that his school performance could be better and want a medication that will assure it. In most of these cases "the truth is that the son does not have the superior IQ of his parents", though the boy may have other qualities that surpass those of his parents - he may be "handsome, charming, athletic, graceful". McHugh sees his job as trying to get the parents to "forget about adjusting him to their aims, with medication or anything else".

When I spoke with him on the phone, McHugh expanded on this point: "Maybe it's wrong-headed trying to fit people into the world, rather than trying to make the world a better place for people. And if the idea is that the only college your child can go to is Harvard, well, maybe that's the idea that needs righting."

If Alex, the Harvard student, and Paul Phillips, the poker player, consider their use of neuroenhancers a private act, Nicholas Seltzer sees his habit as a pursuit that aligns him with a larger movement for improving humanity. Seltzer's job as a researcher at a defence-oriented thinktank in northern Virginia has not left him feeling as intellectually alive as he would like. To compensate, he writes papers in his spare time on subjects like "human biological evolution and warfare". Seltzer, 30, told me he worried that he "didn't have the mental energy, the endurance, the... the sponginess that I seem to recall having when I was younger".

This is not something you notice when you talk to Seltzer. And though our memory is probably at its peak in our early 20s, few 30-year-olds are aware of a deficit. But Seltzer considers himself a transhumanist, in the mould of the Oxford philosopher Nick Bostrom and the futuristic writer and inventor Ray Kurzweil. Transhumanists are interested in robots, cryogenics and living a really, really long time; they consider biological limitations that the rest of us might accept, or even appreciate, as creaky obstacles to be aggressively surmounted. On the ImmInst (Immortality Institute) forums, Seltzer and other members discuss life-extension strategies and the potential benefits of cognitive enhancers. Some members, Seltzer among them, use a drug called piracetam, which was first marketed by a Belgian pharmaceutical company in 1972 and in recent years has become available in the US from retailers that sell supplements. Although not approved for any use by the FDA, piracetam has been used experimentally on stroke patients - to little effect - and on patients with a rare neurological condition called progressive myoclonus epilepsy, for whom it proved helpful in alleviating muscle spasms. Data on piracetam's benefits for healthy people is virtually nonexistent, but many users believe that the drug increases blood flow to the brain.

Using neuroenhancers, Seltzer said, "is like customising yourself - customising your brain". For some people, he added, it was important to enhance their mood, so they took antidepressants; but for people like him it was more important "to increase mental horsepower". He said: "It's fundamentally a choice you're making about how you want to experience consciousness." Whereas the 1990s had been about "the personalisation of technology", this decade was about the personalisation of the brain - what some enthusiasts have begun to call "mind hacking".

Of course the idea behind mind hacking isn't exactly new. Sir Francis Bacon consumed everything from tobacco to saffron in the hope of goosing his brain. Balzac reputedly fuelled 16-hour bouts of writing with copious servings of coffee, which, he wrote, "chases away sleep and gives us the capacity to engage a little longer in the exercise of our intellects". Sartre dosed himself with speed in order to finish Critique of Dialectical Reason. Seltzer and his interlocutors on the ImmInst forum are just the latest members of a seasoned cohort, even if they have more complex pharmaceuticals at their disposal.

I eventually met Seltzer in an underground food court not far from the Pentagon. He's slim, with a shaved head, and he spoke precisely, rarely stumbling over his words. I asked him if he had any ethical worries about smart drugs. After a pause, he said that he might have a concern if somebody popped a neuroenhancer before taking a licensing exam that certified him as, say, a brain surgeon, and then stopped using the drug. Other than that he couldn't see a problem. He said that he was a firm believer in the idea that "we should have a fair degree of liberty to do with our bodies and our minds as we see fit, so long as it doesn't impinge on the basic rights, liberty and safety of others". He argued: "Why would you want an upward limit on the intellectual capabilities of a human being? And, if you have a very nationalist viewpoint, why wouldn't you want our country to have the advantage over other countries, particularly in what some people call a knowledge-based economy?" He went on: "Think about the complexity of the intellectual tasks that people need to accomplish today. Just trying to understand what Congress is doing is not a simple thing! The complexity of understanding the gamut of scientific and technical and social issues is difficult. If we had a tool that enabled more people to understand the world at a greater level of sophistication, how can we prejudice ourselves against the notion simply because we don't like athletes to do it? To me it doesn't seem like the same question. And it deserves its own debate."

Seltzer had never had a diagnosis of any kind of learning disorder. But he added: "Though I wouldn't say I'm dyslexic, sometimes when I type prose, after I look back and read it, I've frequently left out words or interposed words, and sometimes I have difficulty concentrating."

As a student Seltzer used both Adderall and piracetam. Now, after a hiatus of several years, he has recently resumed taking neuroenhancers. In addition to piracetam, he took a stack of supplements that he thought helped his brain to function: fish oils, five antioxidants, a product called ChocoMind and a number of others, all available at the health-food store. He was thinking about adding modafinil, but hadn't yet. For breakfast every morning he concocted a slurry of oatmeal, berries, soy milk, pomegranate juice, flaxseed, almond meal, raw eggs and protein powder. The goal behind the recipe was efficiency: to rely on "one goop you could eat or drink that would have everything you need nutritionally for your brain and body. I wanted to be able to keep it down - that was it." (He told me this in the kitchen of his apartment; he lives with a roommate, who walked in while we were talking, listened perplexedly for a moment, then put a frozen pizza in the oven.)

Seltzer's decision to take piracetam was based on his own online reading, which included medical-journal abstracts. He hadn't consulted a doctor. Since settling on a daily regime of supplements, he had sensed an improvement in his intellectual work and his ability to engage in stimulating conversation. He continued: "I feel I'm better able to articulate my thoughts. I'm sure you've been in the zone - you're having a really exciting debate with somebody, your brain feels alive. I feel that more. But I don't want to say that it's this profound change."

I asked him if piracetam made him feel smarter, or just more alert and confident - a little better equipped to marshal the resources he naturally had. "Maybe," he said. "I'm not sure what being smarter means, entirely. It's a difficult quality to measure. It's the Gestalt factor, all these qualities coming together - not only your ability to crunch some numbers, or remember some figures or a sequence of numbers, but also your ability to maintain a certain emotional state that is conducive to productive intellectual work. I do feel I'm more intelligent with the drugs, but I can't give you a number of IQ points."

The effects of piracetam on healthy volunteers have been studied even less than those of Adderall or modafinil. Most peer-reviewed studies focus on its effects on dementia or on people who have suffered a seizure or a concussion. Many of the studies that look at other neurological effects were performed on rats and mice. Piracetam's mechanisms of action are not understood, though it may increase levels of the neurotransmitter acetylcholine. In 2008 a committee of the British Academy of Medical Sciences noted that many of the clinical trials of piracetam for dementia were methodologically flawed. Another published review of the available studies of the drug concluded that the evidence "does not support the use of piracetam in the treatment of people with dementia or cognitive impairment", but suggested that further investigation might be warranted. I asked Seltzer if he thought he should wait for scientific ratification of piracetam. He laughed. "I don't want to," he said. "Because it's working."

It makes no sense to ban the use of neuroenhancers. Too many people are already taking them, and the users tend to be educated and privileged people who proceed with just enough caution to avoid getting into trouble. Besides, Anjan Chatterjee is right that there is an apt analogy with plastic surgery. In a consumer society like ours, if people are properly informed about the risks and benefits of neuroenhancers, they can make their own choices about how to alter their minds, just as they can make their own decisions about shaping their bodies.

Still, even if you acknowledge that cosmetic neurology is here to stay, there is something dispiriting about the way the drugs are used - the kind of aspirations they open up, or don't. Jonathan Eisen, an evolutionary biologist at the University of California, Davis, is sceptical of what he mockingly calls "brain doping". During a recent conversation, he spoke about colleagues who take neuroenhancers in order to grind out grant proposals. "It's weird to me that people are taking these drugs to write grants," he said. "I mean, if you came up with some really interesting paper that was spurred by taking some really interesting drug - magic mushrooms or something - that would make more sense to me. In the end you're only as good as the ideas you've come up with."

But it's not the mind-expanding 1960s any more. Every era, it seems, has its own defining drug. Neuroenhancers are perfectly suited to the anxiety of white-collar competition in a floundering economy. And they have a synergistic relationship with our multiplying digital technologies: the more gadgets we own, the more distracted we become and the more we need help in order to focus. The experience that neuroenhancement offers is not, for the most part, about opening the doors of perception, or about breaking the bonds of the self, or about experiencing a surge of genius. It's about squeezing out an extra few hours to finish those sales figures when you'd really rather collapse into bed; getting a B instead of a B-minus on the final exam in a lecture class where you spent half your time texting; cramming for the GREs (postgraduate entrance exams) at night, because the information-industry job you got after college turned out to be deadening. Neuroenhancers don't offer freedom. Rather, they facilitate a pinched, unromantic, grindingly efficient form of productivity.

Last winter, I spoke again with Alex, the Harvard graduate, and found that, after a break of several months, he had gone back to taking Adderall - a small dose every day. He felt that he was learning to use the drug in a more "disciplined" manner. Now, he said, it was less about staying up late to finish work he should have done earlier, and more "about staying focused on work, which makes me want to work longer hours". What employer would object to that?



Ampakines
Urine tests?
Modafinil.com
Rasagiline.com
New smart drugs
Smart and happy?
Donepezil (Aricept)
Cosmetic neurology?
Methylphenidate (Ritalin)
The race to save memories
New smart drugs/nootropics
Smart drugs and aging brains
Smart drugs and mind control
Scepticism about smart drugs
Mood and cognitive performance
Modafinil (Provigil, Alertec, Vigicer)
Alzheimer's Disease: resources and hotlinks


Smart Drugs?
Refs
SMART DRUGS 2: REVIEW

no pain, no gain?