2006-01-08
Unmesh Kher

If you haven't already heard the term nootrope, better jot it down. Chances are you'll hear it a lot in the future. A marriage of the Greek words noos, for "mind," and tropein, for "toward," it refers to drugs that enhance mental performance—popularly known as smart drugs. Nootropes aren't new. Amphetamines, first synthesized by a German chemist in 1887 and used in over-the-counter inhalers by the 1920s, were doled out generously during World War II to Allied and German troops to keep them alert. Military pilots still take dextroamphetamine, or go pills, to stay in fighting form on long missions. But in the post-Viagra era, many neurologists believe—and ethicists fear—that scientific advances and social changes may have set the stage for a new age of cosmetic nootropy.

Indeed, some argue that the era is well under way. There's already a lively market for brain boosters. Herbs and supplements with names like Focusfactor and Brain Quicken clutter health-store shelves and the Internet, often with little scientific basis for their claims. Pill popping in some circles has become as American as SAT-prep classes. Students and professionals in growing numbers are taking potentially addictive stimulants like Ritalin to focus their minds and bolster their memory.

The latest addition to that budding pharmacopoeia is a narcolepsy drug called modafinil that was approved two years ago to help shift workers stay alert. And there's a lot more in the pipeline. Neurologists have made rapid progress unraveling the molecular underpinnings of memory and attention, and drug companies are testing dozens of compounds derived from those discoveries to treat cognitive ailments like Alzheimer's disease and schizophrenia.

Memory Pharmaceuticals in Montvale, N.J., for instance, is developing drugs that boost the expression of genes essential to shoring up the connections among neurons—the physical process that is thought to turn immediate experiences into long-term memories. Cortex Pharmaceuticals in Irvine, Calif., meanwhile, is testing compounds that accomplish something similar more indirectly. Those molecules amplify the response of brain chemicals called AMPA receptors, among the first players in a long biochemical cascade that takes place in the neuron as it encodes memory. The first of those ampakine molecules has been shown in a recent study to boost the attention and mental performance of healthy, sleep-deprived men. The more powerful compounds in Cortex's untested arsenal, says CEO Roger Stoll, may bolster long-term memory without inducing the jittery side effects of drugs like Ritalin and caffeine.

Drugs already on the market, notably those that treat Alzheimer's disease, have been shown in small studies to improve the performance of healthy brains, though not by much. (Most of the research to date has been carried out on patients suffering from cognitive deficits.) "It's not like you start out with an IQ of 100 and get an IQ of 140 after taking these drugs," says Dr. Anjan Chatterjee, a neurologist at the University of Pennsylvania.

Ritalin-type drugs, which have a broadly stimulating effect on the nervous system, clearly improve attention and memory. According to a 2002 study of helicopter pilots operating flight simulators, so does donepezil, a drug that raises levels of the neurotransmitter acetylcholine. In another study, men on 200 mg of modafinil did better at mentally challenging games than subjects taking a placebo. But those results must be kept in perspective. Research at the Walter Reed Army Institute of Research in Silver Spring, Md., found that neither modafinil nor the military pilots' go pills were any better than several cups of coffee at restoring the attention and performance of sleep-deprived people.

If the effects are that mild, what are ethicists so worried about? Almost everything. "As our society becomes more competitive and specialized," says Chatterjee, "even the perception that these medicines provide a slight advantage can drive demand." If new and more effective drugs have few immediately discernible side effects, patients will probably pressure doctors to prescribe them. And as their usage spreads, people may feel forced to take them just to keep up. Would the means to pay for them determine who gets them? Would the rich get smarter and the poor fall further behind? What effects would such drugs have on the personality and mental health of users in the long run? The tendency to forget some things, for example, may be a big part of emotional stability and efficient problem solving.

Those issues don't seem to bother the Americans who pop pills and snap up supplements touted as brain enhancers. The latter are often a waste of money. Studies examining the cognitive benefits of supplements have either proved inconclusive or shown only modest effects. There's some evidence that the popular herb ginkgo biloba boosts cerebral blood flow and improves mental functioning, particularly when taken with ginseng. But there's also evidence that it doesn't.

Some of the most popular brain supplements, including deanol, are stimulants, but they have not been shown to improve cognition. "Americans like to have the five-Starbucks-triple-latte effect," says complementary-medicine guru Dharma Singh Khalsa, who sells his own line of "brain longevity" supplements. He recommends a regimen of antioxidants like vitamins E and C and co-enzyme Q10 to keep the brain healthy. Beyond that, one of his favorite nootropic formulations is a combination of ginkgo, phosphatidylserine (a molecule essential to the health of neural-cell membranes) and omega-3 fats (found in fish oils). But Khalsa emphasizes that nine-tenths of the mental boost people seek can be had by eating well, staying mentally and physically active and keeping stress at bay.

And if that doesn't help, you can always try a cup of joe.

SCHOOLYARD DRUGS Adderall and Ritalin, two drugs widely used to treat attention-deficit disorders, can focus healthy minds as well. These potentially addictive stimulants are increasingly abused by students and professionals—so much so that the U.S. government now considers them "drugs of concern"

Provigil, otherwise known as modafinil, was approved to help narcoleptics and shift workers stay awake. Lately it has joined the ranks of Ritalin as a popular performance aid. Some recent studies suggest it may indeed boost attention and mental acuity

NEW BRAIN BOOSTERS Some drugs for treating Alzheimer's disease increase the levels of the neurotransmitter acetylcholine, which plays a key role in attention and memory. One of the drugs, donepezil, was shown in a study of helicopter pilots to enhance mental performance. These drugs, however, are not widely abused

MEANWHILE, IN HEALTH STORES... ...the shelves are filled with herbs and supplements advertised as brain boosters. Few, if any, clinical trials have assessed their efficacy, but here's what we know about some of the more popular ingredients in these concoctions

Some studies suggest ginkgo biloba, especially in combination with panax ginseng, can boost mental performance

Found in plants like the common snowdrop, galantamine is approved by the FDA as the Alzheimer's drug Razadyne. It's marketed to healthy people as a memory enhancer, but no reliable studies support the claim

Derived from a chemical found in the periwinkle, vinpocetine increases blood circulation in the brain. Will taking it make you smarter or more attentive? No one really knows

Derived from the Chinese club moss, huperzine A works like donepezil and galantamine. But there is no evidence it helps young, healthy brains work better

Many swear by the memory-boosting power of phosphatidylserine, and studies suggest it may aid those with age-related problems

Bacopa monniera, or brahmi, has not yet been proved to make anyone any smarter

http://www.time.com/time/magazine/article/0,9171,1147202,00.html