Turbocharging The Brain
Will a pill at breakfast improve concentration and memory -- and will it do so without long-term detriment to your health?
The symbol H+ is the code sign used by some futurists to denote an enhanced version of humanity. The plus version of the human race would deploy a mix of advanced technologies, including stem cells, robotics, cognition-enhancing drugs, and the like, to overcome basic mental and physical limitations.
The notion of enhancing mental functions by gulping down a pill that improves attention, memory and planning -- the very foundations of cognition -- is no longer just a fantasy shared by futurists. The 1990s, proclaimed that decade of the brain by President George H. W. Bush, has been followed by what might be labeled "the decade of the better brain."
Obsession with cognitive enhancers is evidenced in news articles hailing the arrival of what are variously called smart drugs, neuroenhancers, nootriopics or even "Viagra for the brain." From this perspective, an era of enhancement has already arrived. College students routinely borrow a few pills from a friend's Ritalin prescription to pull an all-nighter. Software programmers on deadline or executive trying to maintain a mental edge gobble down modafinil, a newer generation of pick-me-ups. Devotees swear that the drugs do more than induce the wakefulness of a caramel macchiato, providing instead the laserlike focus needed to absorb the nuances of organic chemistry or explain the esoterica of collateralized debt obligations.
An era of enhancement may also be advanced by scientists and drugmakers laboring to translate research on the molecular basis of cognition into pharmaceuticals meant specifically to improve mental performance -- mainly for people suffering from dementias. But a drug that works for Alzheimer's or Parkinson's patients might inevitably be prescribed by physicians far more broadly in an aging population with milder impairments. Widely publicized debates over the ethics of enhancement have reinforced the sense that pills able to improve cognition will one day be available to us all.
Academic and news articles have asked whether cognitive enhancers already give some students an unfair advantage when taking college entrance exams or whether employers would step over the line if they required ingestion of these chemicals to meet a company's production deadlines.
But even as articles are published on the "boss turns pusher," doubts have arisen about the reality of drugs for strengthening brainpower. Do current drugs developed for attention problems or excessive sleepiness really allow a student to do better on an exam or an executive to perform flawlessly under sharp questioning from a board of directors? Will any drug that fiddles with basic brain functions ever be safe enough to be placed on pharmacy shelves alongside nonprescription pain relievers and antacids?
Ethical Dissonance
Argumenta about safety, fairness and coercion aside, demand is indeed high for cognitive enhancers that are otherwise prescribed for conditions such as ADHD. Based on government data gathered in 2007, more than 1.6 million people in the U.S. had used prescription stimulants nonmedically during the previous 12 months. Legal medicines in this category include methylphemidate (Ritalin), the amphetamine Adderall, and modafinil (Provigil). On some campuses, one quarter of students have reported using the drugs. And an informal online reader survey by Nature last year showed 20 percent of 1,427 respondents from 60 countries polled about their own use said they had used either methylphenidate, modafinil or beta blockers (the last for stage fright). Overall, a need for improved concentration was the reason cited most frequently. People often manage to acquire the drugs on the Internet or from doctors, who can prescribe medicines approved for one purpose to treat something else (drugmakers, however, cannot legally promote such "off label" uses).
Ingestion of these chemicals will likely grow along with an aging population and an increasingly globalized economy. "If you're 65-year-old living in Boston and your retirement savings have decreased dramatically and you have to stay on the job market and compete with a 23-year-old in Mumbai to stay alert and stay effective, you may feel pressured to turn to these compounds," says Zack Lynch, executive director of the Neurotechnology Industry Organization.
The recent push for ethical guidlines, of course, presumes that these drugs are better than placebos and do in fact improve some aspect of cognition, be it attention, memory or "executive function" (planning and abstract reasoning, for instance). Given that assumption, many argue, it behooves ethicists to consider the ramifications of the popularity of these drugs. Such logic led in 2002 to a new academic discipline, neuroethics, meant in part to address the moral and social questions raised by cognition-enhancing drugs and devices (brain implants and the like).
Taking a highly provocative stand, a group of ethicists and neuroscientists published a commentary in Nature last year raising the prospect of a shift away from the notion of drugs as a treatment primarily for illness. The article suggested the possibility of making psychostimulants widely available to the albe-minded to improve performance in the classroom in the classroom or the boradroom, provided the drugs are judged to be safe and effective enought for healthy people. Citing research demonstrating the benefits of these drugs on memory and various forms of mental processing, the investigators equated pharmaceutical enhancement with "education, good health habits, and information technology -- ways that our uniquely innovative species tries to improve itself."
Six months later one of the article's authors, John Harris, a bioethicist at the Universtiy of Manchester in England, went further in an opinion piece in the British Medical Journal. Harris, editor of the Journal of Medical Ethics, and a book called Enhancing Evolution, noted that if methylphenidate is judged safe enough to be used in children, it should be considered sufficiently innocuous for consumption by adults interested in turbocharging their brains. In a later interview, Harris said he foresaw a gradual loosening of restrictions, and if no safety problems arise, the drug (a controlled substance in the U.S.) could ultimately became an over-the-counter purchase, like asprin.
These musings have not gone unchallenged. Other researchers and ethicists have questioned whether drugs that modulate mental processes will ever have a safety profile that will justify their being dispensed in the same fashion a nonprescription painkiller or coffee or tea.
"People say that cognitive enhancement is just like improving vision by wearing glasses," says James Swanson, a researcher at the University of Carlifornia, Irvine, who was involved with clinical trials for both Adderall and modafinil for ADHD. "I don't think people understand the risks that occur when you have a larger number of people accessing these drugs. Some small percentage will likely become addicted, and some people may actually see mental performance decline. That's the reason I'm opposed to their general use." Along these lines, the British Home Office, the interior ministry, is awaiting a report from an advisory panel on whether the potential harm from nonmedical use of enhancers requires new regulations.
Other scientists assert that the debate may be moot because improving smarts might not be possible through any means but the tedious exercise of cramming for a calculus exam. Some who have tried to develop drugs to reverse the memory loss of dementia doubt whether enhancement of the health is anything but a remote possibility. "I would not worry much about implications of cognitive enhancers in the healthy, because there are no cognitive enhancers to worry about," says Rusiko Bourtchouladze, author of a popular book about the science of memory and a researcher who contributed to the work that led to a Nobel Prize for Eric R. Kandel in 2000. "To talk about cognitive enhancement, it's too, too early and these drugs may not arrive even in our lifetime. There's too much noise about this."
In this view, the complex mix of chemical signals, enzymes and proteins that collaborate to form a memory creates a self-regulating balance that resists tinkering unless disrupted b disease. The decline in thought processes and sense of identity that comes with dementia might be addressable by compensating for losses of key chemicals and might merit the risk of untoward side effects from drug intervention. But upsetting the fragile stasis in the healthy could produce unintended consequences: as just one example, any improvement in long-term memory (the place where recollections of childhood and last year's vacation reside) could be countered by diminished capacity for working memory (the mental scratch pad where your brain stores a telephone number temporarily).
Some critics of those who argue over the ethics of neuroenhancement attribute the current flap to what they call "speculative ethics." This tendency also besets nanotechnology and other technological endeavors in which ethicists, scientists and policy makers are diverted by discussions of the social implications of technologies yet to be invented, be they smart pills or nanorobots run amok. "A significant part of the debate on human enhancement... suffers from inflated expectations and technology hype," notes Maarje Schermer of Erasmus University Rotterdam and her colleagues in the journal Neuroethics.
A Checkered History
The notion that existing drugs might enhance cognition in the healthy dates back for the better part of a century and has produced ambiguous results. Chemist Gordon Alles introduced amphetamine for medical use in 1929, a synthetic drug chemically similar to the Chinese herb ephedrine. (Alles also devised the drug Ecstasy, another amphetamine.) Various forms were dispensed on both sides during World War II to keep soldiers awake and alert and to bolster courage. The Germans and Japanese ingested methamphetamine, while the British and Americans used Benzedrine, a similar drug to Adderall.
Scientists soon wanted to know whether the perceived benefit in performance was genuine. Psychologists assessments by both British and Americans during the 1940s found that users self-rated their performances highly on tests that measured reading speed, multiplication and other factors. But their test scores, in most tasks, were no better than those earned by subjects who ingested caffeine. Performance, in fact, could decline on more complex tasks. "Because of their mood-elevating effects, amphetamines tend to make us feel we are performing especially well, when in fact we are not," says Nicolas Rasmussen, a historian of science at University of New South Wales in Sydney and author of the book On Speed (New York University Press, 2008). "In simplistic lab tests assessing performance on boring tasks, they boost scores by increasing intelligence, but that' not the same as taking a law school exam or flying in combat."
Methylphenidate, a close chemical relative of the amphetamines, emerged in 1956 as a supposedly milder and gentle form of stimulant ("the happy medium in psychomotor stimulation," in the words of the drugmaker), but both its biochemical and psychological effects are similar when adjusted for dose. The halcyon era for amphetamines occurred nearly 40 years ago. U.S. consumption reached as much as 10 billion pills in the late 1960s before the Food and Drug Administration clamped down and labeled them as controlled substances that required a special prescription.
In the mid-1990s the growing use of methylphenidate for treatment of ADHD prompted researchers to deploy novel brain-imaging techniques and sophisticated neuropsychological tests to examine effects of the drug in healthy subjects, supplying a baseline for comparison with patients with ADA and other neuropsychiatric disorders. A 1997 paper in Psychopharmacology by Barbara Sahakian, Trevor Robbins and their colleagues at the University of Cambridge showed that methylphenidate improved cognitive performance on several measures (spatial working memory and planning, in particular) in a group of rested, healthy young males but not on others, including attention and verbal fluency. As testing progressed, the volunteers seemed to make more errors in their responses. Perhaps because of impulsivity induced by effects of the drug.
The same researchers found little cognitive benefit in healthy elderly males. And in 2005 a group at the University of Florida Medical School at Gainesville could not turn up any cognitive boost from the drug among 20 sleep-deprived medical students. Another impediment to methylphenidate ever being placed alongside NoDoz and other caffeine pills is its potential for causing cardiac arrhythmias and for abuse as a recreational drug. Addiction is rare with normal dosing. But in the 1970s methylphenidate users routinely became addictied after inhaling or injecting the drug that they called "West Coast."