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December 20, 2007

Forget sports doping. The next frontier is brain doping.

As Major League Baseball struggles to rid itself of performance-enhancing drugs, people in a range of other fields are reaching for a variety of prescription pills to enhance what counts most in modern life.

Despite the potential side effects, academics, classical musicians, corporate executives, students and even professional poker players have embraced the drugs to clarify their minds, improve their concentration or control their emotions.

"There isn't any question about it -- they made me a much better player," said Paul Phillips, 35, who credited the attention deficit drug Adderall and the narcolepsy pill Provigil with helping him earn more than $2.3 million as a poker player.

The medicine cabinet of so-called cognitive enhancers also includes Ritalin, commonly given to schoolchildren for attention deficit hyperactivity disorder, and beta blockers, such as the heart drug Inderal. Researchers have been investigating the drug Aricept, which is normally used to slow the decline of Alzheimer's patients.

The drugs haven't been tested extensively in healthy people, but their physiological effects in the brain are well understood.

They are all just precursors to the blockbuster drug that labs are racing to develop.

"Whatever company comes out with the first memory pill is going to put Viagra to shame," said University of Pennsylvania bioethicist Paul Root Wolpe.

Unlike the anabolic steroids, human growth hormone and blood-oxygen boosters that plague athletic competitions, the brain drugs haven't provoked similar outrage. People who take them say the drugs aren't giving them an unfair advantage but merely allow them to make the most of their hard-earned skills.

In the real world, there are no rules to prevent overachievers from using legally prescribed drugs to operate at peak mental performance. What patient wouldn't want their surgeon to be completely focused during a life-or-death procedure?

"If there were drugs for investment bankers, journalists, teachers and scientists that made them more successful, they would use them too," said Charles E. Yesalis, a doping researcher and emeritus professor at Pennsylvania State University. "Why does anyone think this would be limited to an athlete?"

The growth of the brain drugs bears a striking resemblance to the post-World War I evolution of plastic surgery -- developed to rehabilitate badly disfigured soldiers but later embraced by healthy people who wanted larger breasts and fewer wrinkles.

The use of cognitive-enhancing drugs has been well documented among high school and college students. A 2005 survey of more than 10,000 college students found 4% to 7% of them tried ADHD drugs at least once to remain focused on exams or pull all-nighters. At some colleges, more than one-quarter of students surveyed said they had sampled the pills.

The ubiquitous mental stimulant is coffee, and a morning jolt is sufficient for many. But as scientists were developing drugs to treat serious brain disorders, they found more potent substances.

Sharon Morein-Zamir, a psychologist at Cambridge University who writes about the ethics of brain enhancement, said her interest in the medications was largely academic. But when someone she knew who had been taking Provigil for a neurological condition offered her some pills, Morein-Zamir's curiosity was piqued.

"I knew the literature and wondered what it felt like," she said.

The drug helped her focus as she worked at her computer for hours straight. But she wondered if it was a placebo effect.

"Maybe I would have gotten it done anyway," said Morein-Zamir, who launched an Internet poll Wednesday to ask scientists about their use of brain-enhancing drugs.

Philips, the poker player, started using Adderall after he was diagnosed with ADHD five years ago and later got a prescription for Provigil to further improve his focus. ADHD drugs work by increasing the level of the brain chemical dopamine, which is thought to improve attention. Provigil's mechanism of action is not well understood, but boosting the effect of dopamine is thought to be part of it.

The drugs improved his concentration during high-stakes tournaments, he said, allowing him to better track all the action at his table.

"Poker is the sort of game that a lot of people can play well sporadically, but tournaments are mostly won by people who can play close to their best at all times," he said. "It requires significant mental effort to play in top form for 12 hours a day, five days in a row."

In the world of classical music, beta blockers such as Inderal have become nearly as commonplace as metronomes.

The drugs block adrenaline receptors in the heart and blood vessels, helping to control arrhythmias and high blood pressure. They also block adrenaline receptors in the brain.

"You still have adrenaline flowing in your body, but you don't feel that adrenaline rush so you're not distracted by your own nervousness," said Dr. Bernd F. Remler, a neurologist at the Medical College of Wisconsin in Milwaukee.

That's why Sarah Tuck, a veteran flutist with the San Diego Symphony, takes them to stave off the jitters that musicians refer to as "rubber fingers."

"When your heart is racing and your hands are shaking and you have difficulty breathing, it is difficult to perform," said Tuck, 41, who discovered them when she began performing professionally 15 years ago.

A survey she conducted a decade ago revealed one-quarter of flutists used the pills before some or all of their performances or in high-pressure situations like auditions. She believes use is now more widespread and estimates that three-quarters of musicians she knows use the drugs at least occasionally.

Prescriptions for Inderal and other beta blockers can be readily obtained from physicians. Tuck said some doctors had told her they used the drugs themselves to calm their own nerves before making presentations at medical meetings. Musicians say their drug use is all aboveboard.

"It's not like we're sending our clubhouse attendants to BALCO to get us our Inderal," said double bassist Bruce Ridge, 44, referring to the Bay Area Laboratory Co-Operative that allegedly provided slugger Barry Bonds and other athletes with performance-enhancing drugs.

But cosmetic neurology, as some call it, has risks. Ritalin, Adderall and other ADHD drugs can cause headaches, insomnia and loss of appetite. Provigil can make users nervous or anxious and bring on headaches, while beta blockers can cause drowsiness, fatigue and wheezing.

One Stanford University study found that low doses of Aricept improved the performance of healthy pilots as they tried to master new skills in a flight stimulator, but the side effects -- dizziness and vomiting -- were less than desirable in a pilot.

No one has conducted thorough studies about how brain-boosting drugs would affect healthy people after weeks or months of use, said Dr. Anjan Chatterjee, a neuroscientist at the University of Pennsylvania.

Negative consequences may not be limited to people who popped the pills.

Martha J. Farah, a bioethicist who teaches undergraduates at the University of Pennsylvania, said she was beginning to detect resentment toward students who used the drugs from classmates who did not. She has wondered whether improving productivity through artificial means also might undermine the value of hard work.

In an article published today in the journal Nature, Morein-Zamir and University of Cambridge neuroscientist Barbara J. Sahakian say that clear guidelines are needed to decide what's fair. It may be reasonable to ban the drugs in competitive situations, such as taking the SAT. But in other cases, they wrote, people such as airport screeners, air-traffic controllers or combat soldiers might be encouraged to take them.

With a slew of memory enhancers in development, the issues are not academic.

Memory Pharmaceuticals of Montvale, N.J., for example, is eyeing drugs to combat those pesky "senior moments" that are considered a normal part of aging.

"If there were drugs that actually made you smarter, good Lord, I have no doubt that their use would become epidemic," Yesalis said. "Just think what it would do to anybody's career in about any area. There are not too many occupations where it's really good to be dumb."