Source: New Scientist
Date: 14 May 2005

This pill will make you smarter

HAVING problems performing in the sack? Take Viagra. Got the jitters before that important presentation? Try beta blockers. Need to stay awake to finish that assignment? Pop a Provigil pill.

For those prepared to pay, the growing list of "lifestyle drugs" is shifting the boundaries of what bodies and minds are capable of. Now a small clinical trial of the class of experimental drugs known as ampakines suggests these brain-boosters are destined to blur that line still further by offering improved memory.

The success of the unrelated drug Provigil (also called modafinil) has proved there is a huge market for drugs that can improve mental performance. The US Food and Drug Administration has approved it for treating narcolepsy, sleep apnoea - disrupted breathing during sleep - and the sleepiness caused by shift work. But it is widely taken "off-label" by healthy people to stay awake and alert. Sales of the drug, produced by Cephalon of West Chester, Philadelphia, have more than doubled since 2002, and continue to skyrocket

Some may feel uncomfortable with the increasing availability of such pharmaceutical pick-me-ups, but others see them as no different from performance aids such as palmtop organisers. "Stimulating your brain with a reminder on a Blackberry doesn't seem that different to me from stimulating your brain with a drug," says Arthur Caplan, a bioethicist at the University of Pennsylvania in Philadelphia.

Ampakines work by boosting the activity of glutamate, a key neurotransmitter that makes it easier to learn and encode memory. They change the rules about what it takes to create a memory, and how strong those memories can be, says Gary Lynch of the University of California at Irvine, who invented the drugs. "We all have the same computer," he says, "but we're running with different voltage levels." Ampakines up that "voltage".

The effects can be dramatic, as Julia Boyle at the University of Surrey, UK, and her colleagues have now shown. They tested an ampakine called CX717 on 16 healthy males aged between 18 and 45. The men were given either 100 milligrams, 300 mg or 1000 mg of the drug, or else a placebo. In repeated trials the volunteers cycled through the treatments so that their performance with different amounts of CX717 could be compared directly.

In each test session, the volunteers started with a full night's sleep and the following morning and evening were given a battery of tests. These assessed memory, attention, alertness, reaction time and problem solving. Then, at 11 pm, the volunteers swallowed their pills and stayed up through the night. At midnight, 1 am, 3 am, 5 am and 9 am, they were re-tested on some of the tasks. And at 4 am, cruelly, they were tucked into bed in a darkened room and told to stay awake. The researchers measured heart rate and brainwave activity to monitor how alert the subjects were and whether they fell asleep.

“Even the lowest dose of CX717 improved the wakefulness and cognitive performance of sleep-deprived people”Even the lowest dose of CX717 significantly improved the sleep-deprived volunteers' wakefulness and cognitive performance. And the more ampakine they took, the more they improved and the longer the effect lasted. Roger Stoll, CEO of Cortex, the Irvine-based company in California that owns the drug, announced the trial results at an investors' conference on 4 May. While specifics were scant, he mentioned that in the dark room, for instance, most volunteers taking placebo dozed off within about 3 minutes, while some ampakine users stayed awake for the entire 15-minute test. And on a test of sustained attention, effects kicked in within an hour of consuming the drug, he revealed. Crucially, the subjects suffered none of the jitteriness that comes with caffeine or amphetamines. "It generates a state of cortical wakefulness without stimulation," says Lynch.

CX717 will have to undergo further clinical trials before gaining approval as a drug. Cortex is considering it as a possible treatment for narcolepsy, jet lag, attention deficit hyperactivity disorder, and Alzheimer's disease.

Meanwhile animal studies hint at even more impressive effects. Research on rhesus macaques, carried out for the US military by Sam Deadwyler at Wake Forest University School of Medicine in Winston-Salem, North Carolina, found that sleep-deprived monkeys on CX717 actually performed better on reaction time and accuracy tests than when they were well rested. And non-sleep-deprived monkeys given the drug did better still.
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