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Say No To Smart Drugs?

By James Geary


All across India school children are popping little green and yellow pills--and claiming better grades as a result. Balding executives insist they are regaining lost hair as their memories improve. The country's Science Minister only half-jokingly prescribes the capsules for all members of Parliament. This new wonder drug, launched nationwide in January, is called Memory Plus, a compound derived from the brahmi plant found in India's marshlands. Memory Plus is just one of hundreds of so-called "smart drugs" available around the world, either in the form of over-the-counter herbal mixtures or synthetic prescription formulas. Though these potions vary widely in composition, effectiveness and toxicity, they are all intended to enhance memory by stimulating neural activity.

While the brahmi plant and other natural ingredients have been used for centuries in traditional brain tonics, recent neurobiological research promises whole new classes of compounds designed specifically to treat the memory loss that occurs in neurodegenerative disorders like Alzheimer's disease. These drugs could also have powerful--and controversial--spin-offs in the form of "cognitive enhancers" that enable otherwise healthy individuals to more readily absorb and retain new information. Just as vitamins are commonly taken as dietary supplements, memory pills could soon be available as do-it-yourself brain boosters.

In neurodegenerative disorders like Alzheimer's and Parkinson's, the brain undergoes a rapid and devastating decline. In Alzheimer's patients, the function of the amyloid precursor protein (APP) is disrupted. As a result, another protein--beta amyloid, which is known to be toxic to neurons--accumulates into tangled plaques that prevent communication between synapses. As these plaques build up, neurons throughout the brain are gradually strangled to death. When these neurons are destroyed, levels of crucial neurotransmitters--especially acetylcholine and glutamate--drop. The result: severe and, until recently, irreversible memory loss.

But now that some of the mechanics of memory have been identified, scientists are better able to target potential sites for drug intervention. To date, some 200 different compounds are in various stages of clinical trials for Alzheimer's. One popular treatment strategy involves artificially increasing levels of failing neurotransmitters in the brain. Tacrine, for example, temporarily alleviates memory loss in the early stages of Alzheimer's by blocking an enzyme involved in the breakdown of acetylcholine. It is, however, highly toxic to the liver. A similar drug, called aricept, that is less toxic, has been approved for use in the U.S. and the U.K.

Although these drugs show great promise for treating Alzheimer's, their use is still shadowed by ethical dilemmas. One Alzheimer's sufferer involved in clinical trials for this type of drug in the U.K., for example, was eventually able to remember that she was married. What she failed to remember, however, was that her husband had died several years earlier. This caused untold grief and consternation to both the woman and her family as she waited in vain every day for her deceased spouse to come home from work. Alzheimer's disease associations are now calling for more research into early diagnosis and drugs that delay the onset of the affliction rather than temporarily reverse its effects.

While cognitive enhancers were originally developed for the treatment of Alzheimer's patients, they can also be used as biochemical memory aids for the general population. In today's increasingly competitive marketplace, what struggling medical student or ambitious young lawyer wouldn't welcome the edge a memory pill could offer? And for that matter, what about overworked air traffic controllers, harried taxi drivers and aspiring actors--whose livelihoods depend on being able to flawlessly recall large quantities of information?

Ampakines, another set of experimental compounds still in an early phase of development, work by amplifying the sensitivity of glutamate receptors. Developed by neuropharmacologist Gary Lynch at the University of California at Irvine, ampakines could be effective in enhancing short-term recall not only in Alzheimer's patients, but in healthy individuals. In studies to be published later this spring, Lynch and colleagues report that young men scored up to 20% higher in certain standard tests of learning and memory. In a separate study, men over the age of 60 doubled their scores in similar tests. Should further clinical evaluation confirm these results, Cortex Pharmaceuticals--a company Lynch co-founded--could be expected to rush the new drugs to market.

But some researchers suggest the hype around smart drugs is vastly overblown. The brain, they argue, already functions at or near its maximum limits. "Memory evolved over about a hundred million years," says Swiss-born Cesare Mondadori, director of central nervous system research at the pharmaceutical firm Hoechst Marion Roussel in Bridgewater, New Jersey. "If it could be improved by adding a little more neurotransmitter here or there, nature would have done it long ago. You can fan the flames, but you can't add any more fuel to the fire."

Other scientists are convinced that smart drugs will work--and that demand will be enormous. Says James McGaugh, director of the Center for the Neurobiology of Learning and Memory at the University of California at Irvine: "On the evidence of animal experiments, I'm confident that drugs with strong memory-enhancing capabilities will be developed for human beings. When such drugs arrive, I believe they will be widely used."

If this scenario proves correct, could drug testing become mandatory at universities, as it is at the Olympics, to screen out users of cognitive enhancers? Could companies actually require employees to take memory drugs to maximize performance and efficiency? "The danger with smart drugs is: Where does it stop?" says Keith Wesnes, a psychologist and head of the British pharmaceutical consultancy firm Cognitive Drug Research. "Do you start sprinkling them on children's corn flakes?"

If these questions seem like science fiction, they're not. Researchers and clinicians agree that cognitive enhancers will be on the market within the next five to ten years. The Marquess of Halifax, a 17th-century English statesman, once remarked that "the best qualification of a prophet is to have a good memory." Before swallowing any promises of total recall, best remember to read the fine print.



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