[Paleopsych] LAT: Sharper minds

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Sharper minds

    By Melissa Healy
    Times Staff Writer
    December 20, 2004

    It would be hard to imagine improving on the intelligence of computer
    engineer Bjoern Stenger, a doctoral candidate at Cambridge University.
    Yet for several hours, a pill seemed to make him even brainier.
    Participating in a research project, Stenger downed a green gelatin
    cap containing a drug called modafinil. Within an hour, his attention
    sharpened. So did his memory. He aced a series of mental-agility
    tests. If his brainpower would normally rate a 10, the drug raised it
    to 15, he said.

    Brain-boosting drugs --An article on drugs that enhance mental
    performance in Monday's Health section said James L. McGaugh was
    director of the Center for the Neurobiology of Learning and Memory at
    UC Irvine. He is the former director. Dr. Michael Rugg is the

    "I was quite focused," said Stenger. "It was also kind of fun."
    The age of smart drugs is dawning. Modafinil is just one in an array
    of brain-boosting medications -- some already on pharmacy shelves and
    others in development -- that promise an era of sharper thinking
    through chemistry.
    These drugs may change the way we think. And by doing so, they may
    change who we are.
    Long-haul truckers and Air Force pilots have long popped amphetamines
    to ward off drowsiness. Generations of college students have swallowed
    over-the-counter caffeine tablets to get through all-nighters. But
    such stimulants provide only a temporary edge, and their effect is
    broad and blunt -- they boost the brain by juicing the entire nervous
    The new mind-enhancing drugs, in contrast, hold the potential for more
    powerful, more targeted and more lasting improvements in mental
    acuity. Some of the most promising have reached the stage of testing
    in human subjects and could become available in the next decade, brain
    scientists say.
    "It's not a question of 'if' anymore. It's just a matter of time,"
    said geneticist Tim Tully, a researcher at Cold Spring Harbor
    Laboratory on Long Island, N.Y., and developer of a compound called
    HT-0712, which has shown promise as a memory enhancer. The drug soon
    will be tested in human subjects.
    The new brain boosters stem in part from research to develop
    treatments for Alzheimer's disease, spinal cord injuries,
    schizophrenia and other conditions. But they also reflect rapid
    advances in understanding the processes of learning and memory in
    healthy people.
    Developing research
    In the last two decades, scientists have made important discoveries
    about which regions of the brain perform specific functions and how
    those regions work together to absorb, store and retrieve information.
    Researchers also have begun to grasp how and where neurotransmitters
    are manufactured and which ones help perform which mental tasks.
    "There are things cooking here that couldn't have been done one to two
    decades ago," said James L. McGaugh, director of UC Irvine's Center
    for the Neurobiology of Learning and Memory.
    Research has gotten further stimulus from a deep-pocketed investor --
    the U.S. military, which is looking for ways to help pilots and
    soldiers stay sharp under the stress and exhaustion of combat.
    The potential market for cognitive enhancers has never been bigger, or
    more receptive.
    An estimated 77 million members of the baby boom generation will turn
    50 in the next 10 years, joining 11 million who have already passed
    the half-century mark -- a stage at which memory and speed of response
    show noticeable decline.
    Modafinil, the drug that whetted Stenger's powers of concentration, is
    used to treat narcolepsy and other sleep disorders. It is one of three
    prescription medications on the market that have been shown to enhance
    certain mental powers.
    The other two are methylphenidate, marketed under the name Ritalin as
    a remedy for attention deficit disorder, and donepezil, prescribed for
    patients with Alzheimer's.
    Studies have shown that these drugs can produce significant mental
    gains in normal, healthy subjects. None of the three has been approved
    for that purpose. Nevertheless, a growing number of healthy Americans
    are taking them to get a mental edge.
    Some obtain the medications from doctors who write prescriptions for
    "off-label" uses not approved by the Food and Drug Administration -- a
    practice both legal and common. Others buy the drugs through
    unregulated Internet pharmacies.
    Cambridge University psychologist Barbara Sahakian considers modafinil
    (marketed commercially under the name Provigil) especially intriguing.
    Its developers aren't sure exactly how it keeps drowsiness at bay. But
    even in healthy people, the medication appears to deliver measurable
    improvements with few side effects.
    In a series of experiments in 2001, Sahakian and colleagues found that
    in games that test mental skill, subjects who took a 200-milligram
    dose of modafinil paid closer attention and used information more
    effectively than subjects given a sugar pill.
    Confronted with conflicting demands, the people on modafinil moved
    more smoothly from one task to the next and adjusted their strategies
    of play with greater agility. In short, they worked smarter and were
    better at multi-tasking.
    "In my mind, it may be the first real smart drug," Sahakian said. "A
    lot of people will probably take modafinil. I suspect they do
    Donepezil, sold under the name Aricept, also has been found to boost
    the brain function of healthy people. The drug increases the
    concentration of a neurotransmitter called acetylcholine, boosting the
    power of certain electrical transmissions between brain cells.
    In a 2002 study, 18 pilots with an average age of 52 were put through
    seven training flights in a simulator and taught a complex set of
    piloting skills over 30 days. Half took a low dose of donepezil; the
    other half took a placebo. At month's end, all were tested on the
    skills they had learned.
    The pilots on donepezil retained more of the skills than those who
    took the placebo. On the most challenging parts of the test, an
    emergency drill and a landing sequence, their performance was notably
    superior, according to results of the study published in the journal
    Botox for the mind?
    Some scientists predict that the development of even more-effective
    brain-enhancing drugs will usher in an age of "cosmetic neurology."
    "If people can gain a millimeter, they're going to want to take it,"
    said Jerome Yesavage, director of Stanford University's Aging Clinical
    Research Center and an author of the donepezil study.
    Judy Illes, a psychologist at Stanford's Center for Biomedical Ethics,
    said mind-enhancing medicine could become "as ordinary as a cup of
    coffee." This could be good for society, helping people learn faster
    and retain more, she said.
    But it also raises questions: Will the rich get smarter while the poor
    fall further behind? (Drugs such as modafinil can cost as much as $6
    per dose.)
    Will people feel compelled to use the medications to keep up in school
    or in the workplace? In a world where mental function can be tweaked
    with a pill, will our notion of "normal intelligence" be changed
    Mirk Mirkin of Sherman Oaks, 77, a retired marketing manager, would
    like to regain a bit of his old intellectual nimbleness. A member of
    Mensa, a society for people with IQs in the top two percentile of the
    nation, Mirkin is bothered by what he laughingly calls "senior
    moments," such as when a name stubbornly eludes him.
    If a pill could halt the march of forgetfulness without uncomfortable
    side effects, he would probably take it, Mirkin said.
    Mirkin, who proctors tests for admission into Mensa, said he would not
    object if younger people took such pills to pump up their mental
    muscle for the test. "If they physically can handle it and want it bad
    enough, why not?"
    Many college and graduate students want an edge bad enough to take
    Ritalin, even if they do not suffer from attention deficit disorder.
    At campuses, test sites and, increasingly, workplaces across the
    country, people are popping "vitamin R." Some users persuade a doctor
    to prescribe it; others get it from friends who have been diagnosed
    with attention deficit disorder.
    The growing demand for Ritalin, which can be addictive, has prompted
    the U.S. Drug Enforcement Administration to classify it as a "drug of
    On the Internet chat board of the Student Doctor Network, college
    students preparing for medical school admission tests frequently
    discuss the benefits of taking Ritalin or similar drugs on exam day.
    Some students think they have no choice. "You figure you're being
    compared to people who are on Ritalin," said one Los Angeles student
    who frequents the site and recently asked a relative to supply the
    drug. "I just figured it would be more fair if you're on the same
    Eventually, ambitious parents will start giving mind-enhancing pills
    to their children, said McGaugh, the UC Irvine neurobiologist.
    "If there is a drug which is safe and effective and not too expensive
    for enhancing memory in normal adults, why not normal children?" he
    said. "After all, they're going to school, and what's more important
    than education of the young? And what would be more important than
    giving them a little chemical edge?"
    Defense Department scientists are pursuing just such an advantage for
    U.S. combat forces. The Pentagon spends $20 million per year exploring
    ways to "expand available memory" and build "sleep-resistant
    circuitry" in the brain.
    Among its aims: to develop stimulants capable of keeping soldiers
    awake, alert and effective for as long as seven days straight. The
    armed forces have taken leading roles in testing modafinil and
    donepezil as performance enhancers for pilots and soldiers.
    On the horizon are other potential smart drugs, each operating on
    different systems in the brain. If they progress through tests of
    safety and effectiveness, the first of them could be available as
    early as 2008. ([3]See "What's on the horizon?" below).
    Three companies are among the leading contenders in the race to
    develop drugs for memory and cognitive performance: Memory
    Pharmaceuticals Corp. of Montvale, N.J.; Cortex Pharmaceuticals Inc.
    of Irvine; and Helicon Therapeutics Inc., founded by Tully, the
    geneticist at Cold Spring Harbor Laboratory.
    All the new smart drugs are being developed as treatments for
    recognized illnesses such as Alzheimer's -- a requirement for FDA
    approval. But the drug that will make a company and its stockholders
    rich will be the one that treats a disorder that until recently was
    not seen as an illness at all -- "age-associated memory impairment,"
    the mild but progressive forgetfulness that afflicts us all as we get
    The risks involved
    Neuroscientists say two factors could prevent Americans from
    succumbing completely to the seductions of smart pills. First, their
    performance may not live up to expectations. Second, they could have
    side effects, some of them difficult to predict.
    "There's no free lunch," said Tully. Consumers will have to consider
    what level of discomfort or risk they're willing to accept in exchange
    for sharper recall or enhanced powers of concentration.
    The side effect that most neuroscientists fear is not physical
    discomfort, but subtle mental change. Over time, a memory-enhancing
    drug might cause people to remember too much detail, cluttering the
    Similarly, a drug that sharpens attention might cause users to focus
    too intently on a particular task, failing to shift their attention in
    response to new developments.
    In short, someone who notices or remembers everything may end up
    understanding nothing.
    "The brain was designed by evolution over the millennia to be
    well-adapted because of the lives we lead," said Martha Farah, a
    psychologist at the University of Pennsylvania. "Our lives are better
    served by being able to focus on the essential information than being
    able to remember every little detail.... We meddle with these designs
    at our peril."
    Despite such qualms, Farah is drawn to the idea that a mind enriched
    by a life of experience might not have to lose the speed of recall it
    enjoyed in its youth.
    "To have the wisdom of age and the memory of a young person? That'd be
    a very good combination."

    What's on the horizon?
    Smart drugs will probably emerge from among medications developed for
    impairments of the brain and nervous system, including depression and
    schizophrenia, Alzheimer's disease and multiple sclerosis, stroke and
    spinal cord injury. Here are a few under development:
    o   Are designed to amplify the strength of electrical signals between
    brain cells.
    o   Could be the first of the new generation of cognitive enhancers to
    come to market; developed by Cortex Pharmaceuticals Inc., which has
    launched human trials.
    o   One is being tested by the Pentagon as an antidote for sleep
    o   Boosted cognitive function of healthy Swedish medical students in
    a 1997 study.
    Mem compounds
    o   Are designed to strengthen consolidation of long-term memory --
    key to learning new skills.
    o   Are under development by Memory Pharmaceuticals Corp., which has
    begun human testing on three separate Mem compounds as treatment for
    Alzheimer's disease, mild cognitive impairment and depression.
    o   In early animal studies, one Mem compound appeared to restore the
    maze recall of middle-aged rats to youthful levels.
    o   Could come to market by 2008.
    o   Is designed to speed and strengthen the process by which
    short-term memories are committed to long-term storage.
    o   Is under development by Helicon Therapeutics Inc., which plans to
    move from animal testing to trials on humans soon.
    o   Shows particular promise as a drug to aid in the rehabilitation of
    stroke victims and to counter the effects of age-associated memory
    Gene therapy
    o   Genetically engineered cells are implanted deep inside the cortex,
    acting as a miniature biological pump that secretes nerve growth
    factor (NGF), a naturally occurring protein in all vertebrates.
    o   Nerve growth factor revitalizes brain cells that atrophy and
    shrink as their host's age advances.
    o   Biotechnology company Ceregene Inc. has launched early tests of
    the gene therapy on human subjects suffering from the early stages of
    Alzheimer's disease, in hopes of slowing its progress.
    o   UC San Diego neuroscientist Mark Tuszynski, who designed the
    NGF-secreting pump, reported in 2000 that aged monkeys who got the
    implanted cells showed an almost complete restoration of normal cell
    function and size.


    3. http://www.latimes.com/features/health/la-he-smartdrugs20dec20,0,7101336,print.story#horizon

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