Modafinil keeps pilots and astronauts awake, but does it make anyone smarter?
Developed in France in the 1970s, modafinil is a first-line treatment for narcolepsy, flown aboard the International Space Station and used by several militaries instead of amphetamines. Students and office workers also take it as a smart drug, yet the evidence that it sharpens rested brains is decidedly mixed.
The neurophysiologist Michel Jouvet created modafinil, French regulators cleared it in 1994, American ones followed in 1998, and generics arriving in America in 2012. Sold as Provigil among other names, it is swallowed as a tablet and classed as a wakefulness-promoting drug. Doctors prescribe it for narcolepsy, shift work sleep disorder and the daytime drowsiness that can persist in obstructive sleep apnea, where it performs moderately.
Exactly how it works is still not settled. The main action appears to be blocking dopamine reuptake in an unusual way, raising dopamine without the sharp surge produced by cocaine or amphetamine. That helps explain why it carries low potential for addiction and little euphoria, and why the United States lists it only as a Schedule IV controlled substance. It does not cure narcolepsy, a disorder tied to a shortage of the brain chemical orexin, but it can tame the sleepiness.
Beyond the clinic its record is patchier. Trials for adult ADHD have been disappointing: one large Phase III study, possibly using high doses, found it ineffective, with side effects in 86% of participants and 47% dropping out. For fatigue in multiple sclerosis, reviews report only modest benefit. As a cognitive enhancer, gains show up most clearly in people short of sleep, and some users even show impairment on certain tasks. The World Anti-Doping Agency bans it, and athletes in cycling, rowing and track have lost medals after positive tests.
Most people tolerate it well, with headache, nausea, anxiety and insomnia the usual complaints, though rare severe skin reactions such as Stevens-Johnson syndrome can occur. It is ruled out in pregnancy because of a higher risk of birth defects, and it weakens hormonal contraceptives. It is also avoided in some heart conditions because it pushes up heart rate and blood pressure.
Source: Modafinil
