[Paleopsych] LAT: Sharper minds
checker at panix.com
Sat Jan 29 16:47:47 UTC 2005
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.
FOR THE RECORD:
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
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
"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
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
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
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. (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
"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
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.
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
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.
More information about the paleopsych