What if you could pop a pill that made you smarter? It sounds like a Hollywood movie plot, but a new systematic review suggests that the decades-long search for a safe and effective “smart drug” (see below) might have notched its first success. Researchers have found that modafinil boosts higher-order cognitive function without causing serious side effects.

Modafinil, which has been prescribed in the U.S. since 1998 to treat sleep-related conditions such as narcolepsy and sleep apnea, heightens alertness much as caffeine does. A number of studies have suggested that it could provide other cognitive benefits, but results were uneven. To clear up the confusion, researchers then at the University of Oxford analyzed 24 studies published between 1990 and 2014 that specifically looked at how modafinil affects cognition. In their review, which was published last year in European Neuropsychopharmacology, they found that the methods used to evaluate modafinil strongly affected the outcomes. Research that looked at the drug's effects on the performance of simple tasks—such as pressing a particular button after seeing a certain color—did not detect many benefits.

Yet studies that asked participants to do complex and difficult tasks after taking modafinil or a placebo found that those who took the drug were more accurate, which suggests that it may affect “higher cognitive functions—mainly executive functions but also attention and learning,” explains study co-author Ruairidh Battleday, now a medical doctor and Ph.D. student at the University of California, Berkeley.

But don't run to the pharmacy just yet. Although many doctors very likely prescribe the drug off-label to help people concentrate—indeed, a 2008 survey by the journal Nature found that one in five of its readers had taken brain-boosting drugs, and half those people had used modafinil—trials have not yet been done on modafinil's long-term effectiveness or safety. Studies of the drug have been “carried out in a controlled scientific environment and usually only looked at the effects of a single dose,” explains Oxford neuropsychologist and review co-author Anna-Katharine Brem—so no one yet knows whether it is safe for long-term use in healthy people. Nor is it known whether modafinil might lose its edge with repeated use, a phenomenon familiar to many coffee drinkers.

Side effects are another important consideration. Modafinil has been shown to cause insomnia, headache and stomachache in some users. Although these kinds of problems may be worth enduring for a drug that treats an illness, “if you don't have a medical condition, the risks versus benefits change dramatically,” says Sharon Morein-Zamir, a psychologist at the University of Cambridge who studies ethical considerations associated with the use of cognition-enhancing drugs. “For some, the benefits will likely outweigh risks, at least some of the time,” she says, whereas “for others this may not be the case.” A pill you take to ace an exam, for instance, won't do you much good if it also causes a grueling stomachache.

The Search for an Intelligence Drug
People have been searching for ways to boost their brainpower perhaps for all of history. In the past century scientific efforts have revealed a few promising chemicals, but only modafinil has passed rigorous tests of cognitive enhancement.

Caffeine: One of the oldest and most popular stimulants. People recognized caffeine's stimulant properties hundreds (perhaps thousands) of years ago. It can enhance alertness and attention; however, effects are short-lived, and tolerance builds up quickly.

Nicotine: Also a stimulant, used for hundreds of years for a range of medicinal purposes. It is very addictive and has many dangerous side effects.

Amphetamine (Benzedrine, Adderall): First synthesized in 1887. Benzedrine was the first drug to treat hyperactivity in children. Amphetamine can enhance attention and memory by increasing levels of norepinephrine and dopamine in the brain, but the compound can be addictive and comes with a range of side effects, including hyperactivity, loss of appetite, disturbed sleep, even psychosis.

Methylphenidate (Ritalin): First marketed in 1954 and prescribed in the 1960s for treating hyperactivity. It became popular for ADHD in the 1990s. As with amphetamine, it can improve memory and focus for those with ADHD, but it is also used off-label as a study and work aid. Some individuals build up a tolerance to Ritalin over time.

Acetylcholinesterase inhibitor (Aricept): Approved to treat Alzheimer's disease in the 1990s. It has been shown in some studies to enhance memory and attention in healthy individuals.

Modafinil: Originally used to treat narcolepsy. It can also enhance cognitive function, especially when completing difficult tasks. Experts are not quite sure how it works or what long-term effects would look like.

Should Everyone Take Cognition-Enhancing Drugs?
As is the case with all medications, cognition-enhancing drugs affect different people in various ways. Setting aside the ethical questions about brain boosters, here is a look at groups who may deserve special consideration.

CHILDREN AND TEENS. Cognition-enhancing drugs could present unique risks to the developing brain. Several clinical trials found modafinil to be safe when given to children with attention-deficit/hyperactivity disorder (ADHD), but the trials lasted only a few months, making it difficult to ascertain the potential effects of long-term use. In a 2014 review article examining the biochemical effects of modafinil and other common “smart drugs,” researchers at the University of Delaware and Drexel University raised concerns that the use of these drugs could affect the developing brain's ability to adapt to new situations and might increase the risk for addictive behaviors.

PEOPLE WITH LOWER IQs. Research suggests thatcognition-enhancing drugs offer the greatest performance boost among individuals with low-to-average intelligence. These findings led University of Oxford researchers to propose in a 2014 paper that if such drugs were selectively given to people who need them most, many ethical concerns about the drugs' use would be alleviated, and they might even reduce opportunity inequality.

SENIORS. Some studies suggest that older adults may not derive much benefit from cognition-enhancing drugs. One study found that methylphenidate (Ritalin), which boosts working memory and attention in young adults, had no effect on performance among healthy elderly volunteers who were asked to perform various cognitive tasks.