Modafinil and Sleep Response

Modafinil doesn't have that problem, and the difference seems to be in its ability to target the brain's sleep response specifically, instead of just flooding the brain with dopamine and adenosine willy-nilly. It does limit dopamine re-uptake to some extent, but it doesn't produce the highs and lows that other stimulants do. The reason could be that it simply produces a lighter dopamine response -- there's less of it flooding the brain. It could also be that modafinil prevents the re-uptake of the neurotransmitter noradrenaline by neurons that specifically trigger sleep, and that this is a stronger effect than the dopamine response. The dopamine could just be a low-grade, ancillary effect.

Aside from the dopamine and noradrenaline, experts believe that modafinil targets the neurotransmitter GABA -- the brain's primary sleep regulator. It seems to slow GABA's release, interfering with the brain's awareness of when it's time to get some sleep. It probably interferes with the behavior of histamine as well, a chemical that causes drowsiness. And according to some scientists, the big modafinil punch comes in its effect on glutamate, the brain's energy chemical. If modafinil does indeed stimulate the action of glutamate, it would not only cause an overall excited neural response, but it would also effectively block GABA sleepiness signals by creating so much noise.

One of the most mysterious things about modafinil, even in view of its multi-pronged, targeted approach to sleep avoidance, is that it appears to trigger no "sleep debt." People who stay awake for a day or two on modafinil report no need to catch up on sleep when the dose wears off. They can just sleep the usual seven or eight hours and get back in the game. People who take amphetamines typically need to sleep for half a day when the high wears off.

Sleep-avoidance is a huge area of study right now, partly because the market is substantial. Cephalon, the company behind modafinil, sold almost $600 million worth of the stuff in 2005 (all to narcoleptics, of course). With that much money at stake, modafinil isn't the only player in the wake-up game. Researchers are developing and testing all sorts of new ways to keep people alert on limited sleep and even eliminate the need for natural sleep altogether. The idea is to bend sleep to the needs of our lifestyle instead of the other way around.

Cephalon is currently in the final stages of getting a newer version of modafinil to market. This pill offers more hours of wakefulness per dose. The pharmaceutical company Cortex is working with DARPA on a drug code-named CX717, which keeps people awake and alert by triggering increased glutamate activity. Other drugs in the works specifically target histamine. But that's only the beginning. Some researchers are trying to find a way to mimic the rejuvenating effects of eight hours of sleep in just three or four hours. The end result would probably be a pill that will put you to sleep for specific amount of time and then wake you up. You'd be able to pop a three-hour sleep pill or a five-hour sleep pill, depending on what your schedule allows, and wake up feeling like you'd gotten eight hours of the best sleep of your life. In other labs, there are sleep-avoidance machines that deliver a small electric current to a targeted area of the brain to keep it awake and functioning without sleep. The end result of this research could be a piece of head-gear that provides a wake-up jolt at the push of a button.

But this is all child's play compared to the search for the sleep gene. Learn more on the next page.