It’s a play right out of the Twitter era and the family medicine cabinet. “Distracted,” at an off-Broadway theater in New York, examines the ever-shortening attention span of modern life – including the moral conundrum of whether a restive 9-year-old should be given pills to alter his mood.

At one point, an actor breaks from character to address the audience directly and advocate the use of Ritalin and Adderall, two over-the-counter stimulants, which, he says, helped him learn his lines.

The aside encapsulates a growing debate in scientific circles and living rooms across America: Should adults be using so-called “brain-boosting” drugs – normally intended to treat serious medical conditions – to improve concentration and performance?

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College students, of course, have been using stimulants for years: They take modafinil, Adderall, and Ritalin (known on campuses as “vitamin R”) to enhance their memories for exams or to stay up all night and press out a term paper. By one estimate, at least 10 percent of U.S. college students use prescription drugs as study aids.

Now the general adult population is turning to the pills, too, to boost productivity and enhance their mental prowess on the job. Some experts laud the development: They think it’s time to consider making the stimulants legal for brain-boosting functions.

But critics worry it will accelerate a slide toward a drugged society. In an era when people take everything from Viagra to enhance their romance to steroids to enhance their baseball statistics, they argue that the addition of so-called “cognitive enhancement” drugs will only make us more dependent on the pill bottle.

Ultimately, it raises the most fundamental questions about identity and what it means to be human: Are we the sum of our experiences or the sum of our pills? As Carl Elliott writes in his book, “Better than Well: American Medicine Meets the American Dream”: “Today, enhancement technologies are not just instruments for self-improvement, or even self-transformation – they are tools for working on the soul.”

Last summer, Michael Arrington, the founder of the influential technology blog TechCrunch, wrote a post asking, “How many Silicon Valley start-up executives are hopped up on Provigil?” He was referring to the stimulant, which is the brand name for modafinil, that doctors normally prescribe to treat excessive drowsiness associated with narcolepsy and other sleep disorders. “[T]he buzz lately is that it’s the ‘entrepreneur’s drug of choice’ around Silicon Valley,” the post said.

In an online poll in the British science journal Nature last year, answered by 1,400 people in 60 countries, 1 in 5 said they had used drugs for nonmedical reasons “to stimulate their focus, concentration, or memory.” Only about half had a prescription for the drug they were using. A third had bought the drugs over the Internet. And even though about half reported unpleasant side effects, 4 out of 5 “thought that healthy adults should be able to take the drugs if they want to,” Nature reported.

Philip Harvey is one who uses them. A professor of psychiatry and behavioral sciences at Emory University in Atlanta, he regularly flies from Georgia to Europe on business. To prepare for his flight, he takes modafinil. He uses the stimulant to feel alert and rested, despite lost sleep, allowing him to return to his family faster. He has no trouble getting a prescription from his doctor. “From Atlanta, I can get to Europe by 6 a.m. and give a 9 a.m. presentation,” he says. “It lets you go and come back the same day, or go over one day and come back the next.”

Right to choose?

In the current debate over brain boosters, the focal point of much of the discussion has been a commentary in the December issue of Nature. Seven prominent bioethicists noted that the drugs “are ‘disruptive technologies’ that could have a profound effect on human life in the twenty-first century.” While calling for more research to better understand the safety and effectiveness of use in healthy individuals, the piece went on to advocate that “mentally competent adults should be able to engage in cognitive enhancement using drugs.”

In the months since, the paper has met with both hearty approval and deep reservations from scientists and other bioethicists. “Anything that can help our brains deal better with the complex challenges of the twenty-first century is to be not only welcomed but actively sought,” wrote Nick Bostrom, director of the Future of Humanity Institute at the University of Oxford, in a letter to the journal.

The commentary served its purpose to “kick up” a needed discussion, says Henry Greely, a bioethicist and professor of law at Stanford University and one of the coauthors of the Nature commentary. He received far more e-mails about the article than for any other he’s published. The aim, he said, was to argue that “enhancement is not fundamentally a dirty word.”

“I think people should think of [drugs] as just one more of many different ways we try to improve our minds,” Dr. Greely says. “I’m a teacher. I’m in the enhancement business. I’m trying to enhance my students’ brains.”

But others were disappointed with the commentary. “It’s not really a piece of science. It’s an editorial arguing that we should use more drugs,” says George Annas, chairman of the department of Health Law, Bioethics, and Human Rights at Boston University. He wonders why an article taking the other side of the debate didn’t accompany it, and why the authors called for looser strictures on use of the drugs before more is known about them. “The way you make sure they’re not harmful is you do a study before you widely advise people to use them,” he says.

Critics argue more time is needed before the drugs are used as mind enhancers. “The reality [is] that there is very little research to document whether [these drugs] are universally beneficial, whether they could be detrimental, what are the long-term outcomes, what are the side effects,” says Nora Volkow, director of the National Institute on Drug Abuse, a U.S. government agency. “There’s really very, very limited knowledge.”

What troubles Dr. Volkow is how the commentary dismissed the dangers of these drugs, equating taking them with drinking coffee, “which is, to say the least, an irresponsible way to present it and an inaccurate one,” she says.

In March, Volkow published a small preliminary study showing that taking modafinil might be addictive in humans, increasing the levels of dopamine, a neurotransmitter that plays a major role in addiction.

But some worry about other problems. Would workers feel coerced to use enhancement drugs in order to win promotions or even simply to keep their jobs?

“For example, what if hospitals started to demand that medical residents dose up on methylphenidate, a drug used to improve concentration, as a prerequisite for employment?” asks Jacob Appel in an article last year in the Journal of Medical Ethics called “When the boss turns pusher.” Or what if fast-food chains insisted that employees take antidepressants to keep them calm and upbeat?

Employers may face a dilemma. “Denying some individuals the opportunity to enhance in this way clearly undermines their right to do with their bodies as they choose,” he says. “However, to permit some to engage in these enhancements may lead to an inevitable race to the bottom – or top – in which employers and market forces pressure more and more American workers to place their brains at the disposal of their bosses.”

More broadly, some worry that as more brain-enhancing drugs come on the market in the next 10 to 15 years, countries may battle for “neuro competitive advantage” in the workforce. If you’re a 58-year-old person living in Boston who’s competing with a 25-year-old in Mumbai, for instance, you might be tempted to use the drugs – whether or not they’re legal in the U.S., notes Zach Lynch, executive director of the Neurotechnology Industry Organization, a trade group.

Moreover, even if they are illegal, or regulated, enforcing those controls would be difficult. “Living in a global economy, I think it’s going to be very hard to regulate the use of these [drugs] in the future, if they’re safe and effective,” Lynch says.

Brain-boosting drugs are already being considered for another workplace – the military. The Defense Advanced Research Projects Agency is working on “all kinds of drugs to make you stronger, to make you eat less,” says Dr. Annas. “They want soldiers to function for up to five days without sleep. That would certainly require drugs. Whether that would have any long-term consequences, I don’t think anybody knows yet.”

A drug called donepezil, developed to treat Alzheimer’s disease, has been shown to modestly increase memory in healthy people. It may become a Viagra-like hit with baby boomers worried about cognitive decline. Work is also under way to use drugs or other methods to selectively erase memories, something that could be used to ease post-traumatic stress among soldiers returning from war, allowing them to forget what they did on the battlefield. Annas sees problems. “I think we want to have remorse about killing,” he says.

Advocates point out that humans already “enhance” their thinking in a variety of ways, from drinking beverages with caffeine (a known stimulant), to exercising to brighten their mood, to relying on a computer to increase knowledge, to simply getting a good night’s sleep before a big test.

But for some, a caution light goes on when we’re changing the way the brain works, particularly when so little is known about it. “Not only do we not have a model for how our brains do complex tasks, we can’t even imagine one,” Dr. Karl Deisseroth, a neuroscientist at Stanford University, told Wired magazine earlier this year.

Revolution of the brain

At the most fundamental level, the drugs challenge perceptions of who we are. Some people believe the next big scientific revolution will be turning our technological prowess on the world within, notably our brains, rather than the world around us. Neuroscience, which includes the development of brain enhancers, is part of this “revolution.”

In this realm, some experts suggest that using pills to alter thinking or mood comes too close to altering our sense of self. “In seeking by these [biotechnologies] to be better than we are or to like ourselves better than we do, we risk ‘turning into someone else,’ confounding the identity we have acquired through natural gift cultivated by genuinely lived experiences,” wrote Leon Kass in a 2003 report on human enhancement from the President’s Council on Bioethics.

Yet others argue the definition of what is one’s “real” self will be up to the individual – and should be.

“It’s not at all clear that people feel more themselves when they’re unmedicated than when they’re medicated,” says James Hughes, director of the Institute for Ethics and Emerging Technologies in Hartford, Connecticut. “Some people are going to feel more ‘themselves’ when they take the drugs, and some are not going to feel more themselves.”

As drug and biotechnology companies look to expand their products and markets, more possibilities for illicit use may lie ahead. Cephalon Inc. is planning to launch Nuvigil, a longer-lasting version of Provigil, later this year. The company sold nearly US$1 billion of Provigil last year, but the drug is going off patent in 2012. Cephalon says a study shows that Nuvigil works to alleviate jet lag, and it is expected to ask the Food and Drug Administration (FDA) to add jet lag as a new medical condition.

Many argue that more research is needed on existing drugs before we start thinking about new ones. Greely, for one, says we don’t have any “real evidence about the effects, short-term or long-term,” of Adderall and Ritalin, which are both used to treat attention-deficit hyperactivity disorder, on healthy people. As companies seek approval from the FDA for new drugs, if they seem likely to be used for enhancement, “we should require some research on those off-label uses,” he says.

If a drug is truly quite safe, he says, the FDA could make an early decision to permit over-the-counter sales. On the other hand, it also could place tough limits on who could prescribe a particular drug or limit the number of pills per prescription. In the end, if it’s true that we only use a small part of our brain now, people are always going to try to improve on that, Annas says, “and drugs are a way in.”

“But we certainly want to think this through and do careful, controlled studies before we move toward over-the-counter sales.”

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Gemma is a recent Oxford University graduate. As a student of experimental psychology, she wrote three essays a week, in addition to spending 40 hours in lectures and labs. At night she worked for the student newspaper. In her final year things began to pile up but the 22-year-old was reluctant to drop any of her activities. She started taking Modafinil to make possible a life that was fast becoming impossible.

Modafinil is a stimulant most commonly prescribed as a prescription drug to treat sleeping disorders, particularly narcolepsy. But increasingly this drug, and two other stimulants, Ritalin and Adderall, are being bought illegally over the internet by high-achieving, overstretched students in British universities to sharpen their focus, concentration and memory.

Like many other high-flyers who use so-called “study” or “smart” drugs, Gemma felt a desire to be on top of her game all the time. Modafinil helped her to stay awake long enough to complete her assignments.

“I had a few American friends who regularly used Ritalin and sang its praises but I was suspicious of it,” she says. “But my friend bought some Modafinil online, said it was fantastic and could keep you awake for ever so I bought some from him.

“Taking Modafinil meant that I could just keep working. It didn’t make me any more gifted but it meant that my day lasted anything up to 36 hours.”

The other popular stimulants, Ritalin and Adderall, are legally prescribed for children who have been given a diagnosis of attention-deficit hyperactivity disorder (ADHD). But since it has been demonstrated in scientific trials that these drugs can boost cognitive performance, their unofficial use has rocketed.

Yet, even as students pop the pills and brag about their advantages in chat rooms, some experts are asking how much damage they are doing to their bodies. Others are speculating that, if the risks are found to be slight, the use of such drugs could become the norm for the brightest, most competitive young people in our society.

Like many users Gemma soon discovered the downsides. She describes feeling shaky, although “this might just have been me not going to sleep. I didn’t feel tired and I didn’t feel hungry. It stopped my body clock. I lost all track of time and whether I was meant to be eating or not. I would have long bursts of concentration”.

More worryingly, she also experienced bouts of obsession. “One night I made 10 Facebook photo albums for no good reason other than the fact that I was set on doing it,” she says.

Tackling the problem is difficult. Figures that reveal who is taking what are not readily available. Last year the scientific journal Nature published the results of an online survey of 1,400 adults. It showed that 20% of readers had taken “smart drugs”, but no definitive figures exist on the extent of their use in British universities. Research at the University of Michigan in the United States reveals that 8% of American undergraduates have used such drugs at one time or another to improve alertness. Other studies suggest the figure could be as high as one in six.

Emmanuel Akpan-Inwang, a student union welfare officer at the London School of Economics, says that as students approach their exams at the end of the year many are experimenting with “anything that will enhance their performance. “Adderall is the most popular drug at the moment,” he reveals.

Such people include Claire, a 22-year-old final-year Cambridge University philosophy student. She opted to try Adderall, a drug that is composed of mixed amphetamine salts, in the run-up to her second-year exams last year. She had no difficulty getting hold of it.

“I was sitting around in our college rooms with friends and someone mentioned that the engineering students had this drug that they used to help them study,” she says. “A friend who was in the year above had a lot of it, which he had bought on the internet, and so he gave me some.”

She took a capsule the next day before going to the library and was delighted to sail through a highly productive session of study. “I really found my concentration levels went up,” she says. “I thought, oh wow, I’ve been sitting in the library for five hours and haven’t been distracted by people walking around like I usually am. It was very helpful.”

With her finals coming up in a few weeks, she is planning to use Adderall again to keep her concentration at peak levels. Nor are the prices prohibitive: Ritalin costs £290 for 150 10mg pills, Adderall £230 for 120 30mg capsules and Modafinil £75 for 100 200mg doses.

Information on the risks of such drugs is highly anecdotal. Users report side effects such as headaches and depression, but no definitive research has been done on the long-term effects of their use on healthy people. This in itself is worrying many, including Barbara Sahakian, professor of neuropsychology at Cambridge University. Sahakian first became interested in the drugs when, arriving jet lagged at a conference in the United States, she was offered Modafinil. After speaking to her colleagues she discovered the extent to which it, and other similar drugs, were in circulation, both among her academic peers and their students.

In a paper entitled Professor’s Little Helper, she spelt out her concerns. “The trouble is that people in the UK are getting these drugs off the internet,” she says. “That’s worrying, because you are not really sure what you are getting. And even if the drug is pure, you may have another medical condition that means you shouldn’t take it. A person having a bad reaction to one of these drugs is, I think, a horrible accident waiting to happen.”

For other academics, such as John Harris, professor of bioethics at Manchester University, it is only a matter of time before smart pills are available, without prescription, on the high street. “If these drugs are shown to be safe, I can see a time when bright, competitive people will be able to access them as easily as you can get the morning-after pill now,” he says.

Some names have been changed

http://www.timesonline.co.uk

Reviewed By Michael W. Smith, MD

What’s wrong with healthy people taking brain-boosting drugs? Nothing, seven leading scientists and ethicists announced this week, (first published December 2008).

Polls suggest that as many as one in five scientists already take brain-boosting drugs — usually the stimulants Ritalin, Adderall, or Provigil.

And there’s nothing wrong with that, suggest the authors of a provocative editorial in this week’s issue of the science journal Nature.

“We call for a presumption that mentally competent adults should be able to engage in cognitive enhancement using drugs,” they write. The editorial also calls for further research into the risks and benefits of using drugs in this way.

It’s a prominent list of authors:

• Henry T. Greely, JD, professor of law at Stanford University; co-director of the Stanford program in genomics, ethics, and society; and co-director of the Stanford program in law, science, and technology.
• Barbara Jacquelyn Sahakian, PhD, FMedSci, professor of clinical neuropsychology at the University of Cambridge School of Clinical Medicine, England.
• John Harris, DPhil, FmedSci, research director at the University of Manchester Institute for Science, Ethics and Innovation, and research director at the university’s Center for social Ethics and Policy in England.
• Ronald C. Kessler, PhD, professor of health care policy at Harvard Medical School and a member of the U.S. National Academy of Sciences.
• Michael Gazzaniga, PhD, professor of psychology and director for the SAGE Center for the Study of Mind at the University of California Santa Barbara.
• Martha J. Farah, PhD, professor of natural sciences and director of the Center for Cognitive Neuroscience at the University of Pennsylvania.
• Philip Campbell, PhD, editor-in-chief of Nature.

Sahakian and Kessler consult for a number of pharmaceutical companies, but the other authors declare no such ties.

The issue, they say, isn’t for drug companies to make money. They suggest that responsible use of drugs for brain enhancement can be good for society as well as for individuals.

Controversial? You bet. Here’s WebMD’s guide to the issues.

What is brain boosting?

Brain boosting — or, as scientists like to say, cognitive enhancement — means making your brain work better.

There are lots of ways to do this without taking drugs: by reading, for example, getting plenty of sleep, or learning something new, such as a new language.

There are also ways to do this with drugs such as caffeine or the prescription stimulants Ritalin, Adderall, and Provigil. Other drugs, such as beta-blockers (Inderal, for example) may also improve mental function.

There is no such thing as a drug benefit without a drug risk. Caffeine has side effects; so do its sister drugs behind the prescription counter.

The FDA has ruled that the benefits of these prescription drugs outweigh their risks for people suffering certain medical problems. For example, people with attention deficit hyperactivity disorder (ADHD) may get help from Ritalin or Adderall. People with daytime sleepiness due to sleep apnea may get help from Provigil.

These drugs also have effects on healthy people. They can increase attention span, boost memory, and focus thinking.

Use of these drugs without a prescription is illegal. In the U.S., unauthorized sale of these drugs is a felony.

Who uses brain-boosting drugs?

In 2007, Sahakian and colleague Sharon Morein-Zamir surveyed their Cambridge colleagues on the use of brain-boosting drugs. They found a surprising degree of acceptance of the practice, at least in principle.

This led Nature to poll its readers. The poll suggested that one in five Nature readers — mostly scientists — had used stimulant drugs for nonmedical reasons in order to stimulate their focus, concentration, or memory.

Studies suggest that between 5% and 15% of college students use brain-boosting drugs. Most use Ritalin or Adderall while Provigil use remains uncommon. The Nature poll also found that many people take beta-blockers, such as Inderal.

What are the side effects of brain-boosting drugs?

People who take brain-boosting drugs risk obvious problems if they overdose. Brain-boosting drugs also have important interactions with other drugs or substances a person may be using.

For example, Provigil has not been tested in people who drink alcohol. Patients with Provigil prescriptions are advised to avoid drinking alcohol.

The most common side effects reported in the Nature poll were headaches, jitteriness, anxiety, and sleeplessness. About half of those using these drugs reported these side effects, which were often serious enough to make people stop using the drugs.

But even the proponents of cognitive enhancement admit that too little is known about the long-term use of brain-boosting drugs in healthy people. The Nature editorialists call for more research.

Is it cheating or unnatural to use brain-boosting drugs?

Yes, say critics such as Leon R. Kass, MD, chairman of the President’s Council on Bioethics. It is cheating. But even worse, it’s unnatural.

“One major trouble with biotechical (especially mental) ‘improvers’ is that they produce changes in us by disrupting the normal character of human being-at-work-in-the-world … which, when fine and full, constitutes human flourishing,” Kass wrote in 2003. “With biotechnical interventions that skip the realm of intelligible meaning, we cannot really own the transformations nor experience them as genuinely ours.”

This loss, Kass argues, subtracts from our humanity.

But in this week’s Nature editorial, Greely and colleagues say brain boosting is not cheating. It’s not against the rules to drink a double espresso or hire a private tutor, they argue, so why disallow use of brain-boosting drugs?

More importantly, they say, we already live highly unnatural lives.

“Given the many cognitive-enhancing tools we accept already, from writing to laptop computers, why draw the line here and say thus far but no further?”

If other people outperform me because they use brain-boosting drugs, won’t I be compelled to use them? Aren’t brain-boosting drugs unfair to those who don’t use them?

These are tricky questions, Greely and colleagues admit. They say policies should prohibit requiring people to take brain-boosting drugs except where public safety is at stake.

As to fairness, they note that people already have unequal access to brain-enhancing experiences such as private tutoring.

In cases where the drugs are merely used to temporarily boost exam performance, Greely and colleagues suggest that drug use would be unfair. But if the drugs boosted one’s long-term learning, they have less of a problem with unfairness.

“Cognitive enhancement, unlike enhancement for sports competitions, could lead to substantive improvements in the world,” Greely and colleagues suggest.

How would brain-boosting drugs be regulated?

Greely and colleagues suggest that policies regarding cognitive-enhancing drugs should be based on scientific evidence. They call for:

• Accelerated research into the risks and benefits of cognitive enhancement
• Participation of medical and scientific organizations in formulating guidelines
• Education to increase public understanding of cognitive enhancement
• Legal reforms — not new laws — to align existing laws with “emerging social norms and information about safety”

SOURCES: Greely, H. Nature, advance online publication, Dec. 7, 2008. Sahakian, B. and Morein-Zamir, S. Nature, Dec. 20/27, 2007; vol 450 pp 1157-1159. Kass, L. R. President’s Council on Bioethics, “Beyond Therapy: Biotechnology and the Pursuit of Human Improvement,” January 2003. British Medical Association, “Boosting Your Brainpower: Ethical Aspects of Cognitive Enhancements,” November 2007. Maher, B. Nature, April 2008; vol 452: pp 674-675.

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