[ExI] Fwd: [tt] The underground world of “neuroenhancing” drugs

[Bryan Bishop]

---------- Forwarded message ----------
From: Eugen Leitl <eugen at leitl.org>
Date: Wed, Apr 22, 2009 at 2:03 AM
Subject: [tt] The underground world of “neuroenhancing” drugs
To: tt at postbiota.org

http://www.newyorker.com/reporting/2009/04/27/090427fa_fact_talbot?currentPage=all

Brain Gain

The underground world of “neuroenhancing” drugs.

by Margaret Talbot April 27, 2009

Every era has its defining drug. Neuroenhancers are perfectly suited for our
efficiency-obsessed, BlackBerry-equipped office culture.

Keywords Neuroenhancing Drugs; Neuroenhancers; Students; Adderall;
Stimulants; Smart Drugs; Underground

A young man I’ll call Alex recently graduated from Harvard. As a history
major, Alex wrote about a dozen papers a semester. He also ran a student
organization, for which he often worked more than forty hours a week; when he
wasn’t on the job, he had classes. Weeknights were devoted to all the
schoolwork that he couldn’t finish during the day, and weekend nights were
spent drinking with friends and going to dance 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. 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 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 A.D.H.D., and in his
freshman year 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 fifteen milligrams of Adderall most
evenings, usually after dinner, guaranteeing that he would maintain intense
focus while losing “any ability to sleep for approximately eight to ten
hours.” In his sophomore year, he persuaded the doctor to add a
thirty-milligram “extended release” capsule to his daily regimen.

Alex recalled one week during his junior year when he had four term papers
due. Minutes after waking on Monday morning, around seven-thirty, 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 e-mail, “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, I can assure you, that is
common to all intellectually curious students on stimulants.” At eight, he
attended a two-hour meeting “with a group focussed 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 organization; he felt like “a zombie,” but “was there to
insure that the semester’s work didn’t go to waste.” After that, Alex
explained, “I went back to my room to take advantage of my tired body.” 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 twenty-four-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 in a variety of realms—social, romantic, sexual,
extracurricular, résumé-building, academic commitments.” 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, or in order to be an
obvious admit to law school or the first accepted at a consulting firm.” 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 least, most people are to some degree realistic
about it. . . . I don’t think people who take Adderall are aiming to be the
top person in the class. I think they’re aiming to be among the best. Or
maybe not even among the best. At the most basic level, they aim to do better
than they would have otherwise.” He went on, “Everyone is aware of the fact
that if you were up at 3 A.M. 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 “nonmedical” 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’s Substance Abuse
Research Center, reported that in the previous year 4.1 per cent of American
undergraduates had taken prescription stimulants for off-label use; at one
school, the figure was twenty-five per cent. Other researchers have found
even higher rates: a 2002 study at a small college found that more than
thirty-five per cent of the students had used prescription stimulants
nonmedically in the previous year.

Drugs such as Adderall can cause nervousness, headaches, sleeplessness, and
decreased appetite, among other side effects. An F.D.A. 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
benign, in part because they are likely to know peers who have taken the
drugs since childhood for A.D.H.D. 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—especially in the Northeast—are the most frequent
collegiate users of neuroenhancers. Users are also more likely to belong to a
fraternity or a sorority, and to have a G.P.A. of 3.0 or lower. They are ten
times as likely to report that they have smoked marijuana in the past year,
and twenty 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 Web sites—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 8 p.m., it’s 6:30 a.m. and I’ve
barely blinked.” On the Columbia site, a poster with an e-mail address from
CUNY 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?
Will it fuck me up? 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 dissents (“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 organize 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 belaboring a point, trying
to create this airtight argument, when if you just got to your point in a
more direct manner it would be stronger. But with Adderall 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 out of five respondents said that they
did. A majority of the fourteen hundred readers who responded said that
healthy adults should be permitted to take brain boosters for nonmedical
reasons, and sixty-nine per cent 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, 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 25 mg every four hours,
4 times today, and had a great and productive day—with no side effects.”) In
one recent post, a fifty-two-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 a hundred
milligrams 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 with Anjan Chatterjee, a neurologist at the University of
Pennsylvania, in his office, which is tucked inside 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 behavior. In 2004, he coined
the term “cosmetic neurology” to describe the practice of using drugs
developed for recognized medical conditions to strengthen ordinary cognition.
Chatterjee worries about cosmetic neurology, but he thinks that it will
eventually become as acceptable as cosmetic surgery has; 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 are all “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 aging 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.” The day I
visited his office, 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: a pill.

Recently, I spoke on the phone with Barbara Sahakian, a clinical
neuropsychologist at Cambridge University, and the co-author of a December,
2007, article in Nature, “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. She might, justifiably,
have forgone distractions like me, but she had her cell phone with her, and
though it was a weekend morning some industrious person in the Cambridge news
office had reached Sahakian in her hotel room, after she got out of the
shower and before she had to rush to the first session. “We may be healthy
and high-functioning, and think of ourselves that way, but it’s very rare
that we are actually functioning at our optimal level,” Sahakian said. “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, U.K. 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 sympathized with them, but, 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 sixteen healthy elderly volunteers
found that five hundred milligrams 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 thirty 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 U.C.L.A.; she
went on to get a master’s degree in neuroscience at U.C.S.F., and he became
an executive at a software company. Last summer, I had coffee with them in
the Noe Valley neighborhood of San Francisco, and they both spoke with casual
certainty about the coming market for neuroenhancers. Zack, who has a book
being published this summer, called “The Neuro Revolution,” 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, forty per cent or fifty per cent, and
take them up to eighty,” 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 behaviors. In this way, Ritalin and Adderall helped make
A.D.H.D. 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 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 apnea
and “shift-work sleep disorder.” Net sales of Provigil climbed from a hundred
and ninety-six million dollars in 2002 to nine hundred and eighty-eight
million 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 F.D.A. for
distributing marketing materials that presented the drug as a remedy for
tiredness, “decreased activity,” and other supposed ailments. And in 2008
Cephalon paid four hundred and twenty-five million dollars 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 emphasized that Cephalon was not developing
Nuvigil as a neuroenhancer, she noted, “As part of the preparation for some
of these other 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.
Even if today’s smart drugs aren’t as powerful as such drugs may someday be,
there are plenty of questions that need to be asked about them. 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 Americans 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 nineties, he was already a millionaire: a
twenty-something tech guy who had started off writing software, helped found
an Internet portal called go2net, and cashed in at the right moment. He was
cerebral and, at times, brusque. His nickname was Dot Com. On the
international poker-tournament scene—where the male players tend to be either
unabashedly schlumpy or sharply dressed in the manner of a Vegas hotel
manager—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, at U.C. San Diego.
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 focussed for fourteen 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
A.D.H.D., and he began taking Adderall. Within six months, he had won $1.6
million at poker events—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 between two hundred and three hundred milligrams 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 thirty-six, seemed a bit out of place in Bend,
where people spend a lot of time skiing and river rafting. Among the
friendly, faithfully recycling locals, he was making an effort to curb his
caustic side. Still, when I first sent Phillips an e-mail asking him to
explain, more precisely, how Provigil affected him, he couldn’t resist a
smart-ass answer: “More precisely: after a pill is consumed, tiny molecules
are absorbed into the bloodstream, where they eventually cross the
blood-brain barrier and influence the operation of the wetware up top.”

In person, he was more obliging. He picked me up at the Bend airport driving
a black convertible BMW, and we went for coffee at a cheery café called
Thump. Phillips wore shorts and flip-flops and his black T-shirt displayed an
obscure programming joke. “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,” he said. 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 characterize 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 memorization, which didn’t come as easily as it once had. “I stopped
short of memorizing 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 ten thousand seven- and eight-letter
words.” Provigil, he said, helped with the memorization 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 journalist I know, who takes the drug when he has to stay up all
night on deadline, says that it doesn’t help in the phase when he’s trying to
figure out what he wants to say or how to structure a story; but, once he’s
arrived at those insights, it helps him stay intent on completing a draft.
Similarly, a seventy-four-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, the Provigil manufacturer, has publicly downplayed the idea that
the drug can be used as a smart pill. In 2007, the company’s founder and
C.E.O., Frank Baldino, Jr., told a reporter from 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. Only a few studies have been done of Provigil’s
effects on healthy, non-sleep-deprived volunteers, but those studies suggest
that Provigil does provide an edge, at least for some kinds of challenges. In
2002, researchers at Cambridge University gave sixty healthy young male
volunteers a battery of standard cognitive tests. One group received
modafinil; the other got 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 forward, then backward. They
also did better in recognizing repeated visual patterns and on 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.) He found the “arms-race aspect” of cognitive
enhancement distasteful, and didn’t like the idea that parents might force
their kids to take smart pills. He sighed when I suggested that adults, too,
might feel coerced into using the drugs. “Yeah, in a competitive field—if
suddenly a quarter of the people are more equipped, but you don’t want to
take the risks with your body—it could begin to seem terribly unfair,” he
said. “I don’t think we need to be turning up the crank another notch on how
hard we work. But the fact is, the baseline competitive level is going to
reorient around what these drugs make possible, and you can choose to compete
or not.”

In the afternoon, we drove over to Phillips’s house—a big place, handsome and
new, with a sweeping deck overhanging the Deschutes River. Inside, toys were
strewn across the shag carpeting. Phillips was waiting for his wife and
daughters to come home from the swimming pool, and, sitting in his huge,
high-ceilinged living room, he looked a little bored. He told me that he had
recently decided to apply to graduate school in computer programming. It was
going to be hard—getting out all those applications, convincing graduate
programs that he was serious about returning to school. But he had, as he put
it, “exhausted myself on all forms of leisure,” and felt nostalgic for his
last two years of college, when he had discovered computer programming. “That
was the most purely intellectually satisfying period of my whole life,” he
said. “It transformed my brain from being all over the place to a reasonable
edifice of knowledge about something.” Back then, he hadn’t taken any smart
pills. “I would have been a freakin’ dynamo in college if I’d been taking
them,” he said. “But, still, I had to find computers. That made a bigger
difference than anything else—finding something I just couldn’t get enough
of.”

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.” He said, “In the situations where they do help, do they come
with a cost?” As he wrote in a recent letter to Nature, “Most seasoned
physicians have had the sobering experience of prescribing medications that,
despite good intentions, caused bad outcomes.” Given that cognitive
enhancement is a choice, not a necessity, the cost-benefit calculation for
neuroenhancers should probably be different than it is for, say, heart
medications.

Provigil can be habit-forming. In a study published recently in the Journal
of the American Medical Association, a group led by Nora Volkow, the director
of the National Institute on Drug Abuse, scanned the brains of ten 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 Web site 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 “4-5 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 Anjan Chatterjee’s colleague Martha Farah, who is a
psychologist at Penn and the director of its Center for Cognitive
Neuroscience. She has been writing about neuroenhancers for several years
from a perspective that is deeply fascinated and mildly critical, but
basically in favor—with the important caveat that we need to know much more
about how these drugs work. I spoke with her one afternoon at her research
center, which is in a decidedly unfuturistic-looking Victorian house on
Walnut Street, in Philadelphia. Farah, who is an energetic conversationalist,
had bought canned espresso drinks for us. Though she does not take
neuroenhancers, she has found that her interest in them has renewed her
romance with the next best thing: caffeine.

Farah had just finished a paper in which she reviewed the evidence on
prescription stimulants as neuroenhancers from forty 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 memorize 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. The studies on learning showed
that neuroenhancers did improve retention. The benefits were more apparent in
studies 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 that the studies examined 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 color (let’s say orange) written in a different color
(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 color
(which is harder, because our first impulse is to say “orange”). These
studies presented a more mixed picture, but over all 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 A.D.H.D. or
any kind of cognitive impairment.” But, she emphasized, “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. And the effects of neuroenhancers on some vital forms of
intellectual activity, such as abstract thought and creativity, have barely
been studied at all. Farah said that the extant literature was concerned with
“fairly boring kinds of thinking—how long can you stay vigilant while staring
at a screen and waiting for a little light to blink.” She added, “It would be
great to have studies of more flexible kinds of thought.”

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, “Cognitive psychologists have found that there is a trade-off between
attentional focus and creativity. And 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.”

Farah and Chatterjee recently completed a preliminary study looking at the
effect of one ten-milligram dose of Adderall on sixteen students doing
standard laboratory tests of creative thinking. They did not find that this
low dose had a detrimental effect, but both believe that this is only the
beginning of the vetting that must be done. “More and more of our young
people are using these drugs to help them work,” Farah said. “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 focussed 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 and prep courses? At
many colleges, students have begun calling the off-label use of
neuroenhancers a form of cheating. 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 they get their blue books.
And though secretly taking a neuroenhancer for a three-hour exam does seem
unfair, condemning the drugs’ use seems extreme. Even with the aid of a
neuroenhancer, you still have to write the essay, conceive the screenplay, or
finish the grant proposal, and 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 also makes this point: “Equality of opportunity is an explicit
goal of our education system, giving individuals the best chance of achieving
their full potential and of competing on equal terms with their peers.
Selective use of neuroenhancers amongst 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 I.V. drip of synthetic nutrition for
actual food—it may nevertheless 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 toward 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
British Medical Association report offered a similarly upbeat observation:
“Universal access to enhancing interventions would bring up the base-line
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 fifty-five-year-old
in Boston, you have to compete with a twenty-six-year-old from Mumbai now,
and those kinds of pressures are only going to grow,” he began. Countries
other than the U.S. 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 forty-seven 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,
O.K.’ 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—emergency-room doctors, air-traffic controllers—to take them.
(Indeed, the 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
skeptically 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 I.Q. 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-footed 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 has a B.A. from U.C. Davis and a master’s degree in security policy
from George Washington University. But the job that he obtained with these
credentials—as a researcher at a defense-oriented think tank, 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.” He also primes his brain with artificial
challenges; even when he goes to the rest room at the office, he takes the
opportunity to play memory or logic games on his cell phone. Seltzer, who is
thirty, told me that he worried that he “didn’t have the mental energy, the
endurance, the—I don’t know what to properly call this—the sponginess that I
seem to recall having when I was younger.”

Suffice it to say that this is not something you notice when you talk to
Seltzer. And though our memory is probably at its peak in our early twenties,
few thirty-year-olds are aware of a deficit. But Seltzer is the
Washington-wonk equivalent of those models and actors in L.A. who discern
tiny wrinkles long before their agent does. His girlfriend, a technology
consultant whom he met in a museum, is nine years younger, and he was already
thinking about how his mental fitness would stand up next to hers. He told
me, “She’s twenty-one, and I want to stay young and vigorous and don’t want
to be a burden on her later in life.” He didn’t worry about visible signs of
aging, but he wanted to keep his mind “nimble and healthy for as long as
possible.”

Seltzer considers himself a “transhumanist,” in the mold of the Oxford
philosopher Nick Bostrom and the futurist 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 forums—“ImmInst” stands for “Immortality
Institute”—Seltzer and other members discuss life-extension strategies and
the potential benefits of cognitive enhancers. Some of the forum members
limit themselves to vitamin and mineral supplements. Others use Adderall or
modafinil or, like Seltzer, a drug called piracetam, which was first marketed
by a Belgian pharmaceutical company in 1972 and, in recent years, has become
available in the U.S. from retailers that sell supplements. Although not
approved for any use by the F.D.A., 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
are virtually nonexistent, but many users believe that the drug increases
blood flow to the brain.

>From the time I first talked to Seltzer, it was clear that although he felt
cognitive enhancers were of practical use, they also appealed to him on an
aesthetic level. Using neuroenhancers, he said, “is like customizing
yourself—customizing your brain.” For some people, he went on, 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 added,
“It’s fundamentally a choice you’re making about how you want to experience
consciousness.” Whereas the nineties had been about “the personalization of
technology,” this decade was about the personalization of the brain—what some
enthusiasts have begun to call “mind hacking.”

Of course, the idea behind mind-hacking isn’t exactly new. Fortifying one’s
mental stamina with drugs of various kinds has a long history. Sir Francis
Bacon consumed everything from tobacco to saffron in the hope of goosing his
brain. Balzac reputedly fuelled sixteen-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.”
My college friends and I wrote term papers with the sweaty-palmed assistance
of NoDoz tablets. And, before smoking bans, entire office cultures chugged
along on a collective nicotine buzz—at least, if “Mad Men” is to be believed.
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. We sat down at a Formica table in the dim light. Seltzer was slim,
had a shaved head, and wore metal-frame glasses; matching his fastidious
look, 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.” In graduate school, he
obtained a prescription for Adderall from a doctor who didn’t ask a lot of
questions. The drug helped him, especially when his ambitions were relatively
low. He recalled, “I had this one paper, on nuclear strategy. The professor
didn’t look favorably on any kind of creative thinking.” On Adderall, he
pumped out the paper in an evening. “I just bit my tongue, regurgitated, and
got a good-enough grade.”

On the other hand, Seltzer recalled that he had taken piracetam to write an
essay on “the idea of harmony as a trope in Chinese political discourse”—it
was one of the papers he was proudest of. He said, “It was really an
intellectual challenge to do. I felt that the piracetam helped me to work
within the realm of the abstract, and make the kind of associations that I
needed—following this idea of harmony from an ancient religious belief as it
was translated throughout the centuries into a very important topic in
political discourse.”

After a hiatus of several years, Seltzer had recently resumed taking
neuroenhancers. In addition to piracetam, he took a stack of supplements that
he thought helped his brain functioning: 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.” He explained, “Taste was the last thing on my mind; 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 regimen 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
I.Q. 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 U.C. Davis, is skeptical 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 sixties anymore. Every era, it seems, has its
own defining drug. Neuroenhancers are perfectly suited for 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
G.R.E.s 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.

This 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 focussed on
work, which makes me want to work longer hours.” What employer would object
to that?
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