BehindTheMedspeak: Cosmetic Neurology

Margaret Talbot's interesting and instructive article in the latest (April 27, 2009) issue of the New Yorker takes a look at the brave new  world of "neuroenhancing" drugs like Provigil, Adderall, Ritalin, ampakines and piracetam.

Long story short: they work.

Excerpts from the longer story follow.

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Brain Gain — The Underground World of "Neuroenhancing" Drugs

... 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....

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.

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.

Not long ago, I met with Anjan Chatterjee [top], 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.

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.

“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.

... 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.

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.

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.”

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.

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.