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
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.