Modafinil is the world’s first safe “smart drug”, researchers at Harvard and Oxford universities have said, after performing a comprehensive review of the drug. They concluded that the drug, which is prescribed for narcolepsy but is increasingly taken without prescription by healthy people, can improve decision- making, problem-solving and possibly even make people think more creatively.



While acknowledging that there was limited information available on the effects of long-term use, the reviewers said that the drug appeared safe to take in the short term, with few side effects and no addictive qualities.



Modafinil has become increasingly common in universities across Britain and the US. Prescribed in the UK as Provigil, it was licensed in 2002 for use as a treatment for narcolepsy - a brain disorder that can cause a person to suddenly fall asleep at inappropriate times or to experience chronic pervasive sleepiness and fatigue.

Used without prescription, and bought through easy-to-find websites, modafinil is what is known as a smart drug - used primarily by people wanting to improve their focus before an exam. A poll of Nature journal readers suggested that one in five have used drugs to improve focus, with 44% stating modafinil as their drug of choice. But despite its increasing popularity, there has been little consensus on the extent of modafinil’s effects in healthy, non-sleep-disordered humans.



A new review of 24 of the most recent modafinil studies suggests that the drug has many positive effects in healthy people, including enhancing attention, improving learning and memory and increasing something called “fluid intelligence” - essentially our capacity to solve problems and think creatively. One study also showed that modafinil made tasks seem more pleasurable. The longer and more complex the task tested, the more consistently modafinil conferred cognitive benefits, the authors of the review said.

The review points out that negative effects - including one study that showed that people already classed as creative saw a small drop in creativity - were reported in a small number of tasks, but never consistently. It added that the drug exerts minimal effects on mood, and only causes minor side effects such as nausea, headaches and anxiety, although these were also reported by people who took a placebo drug.



Other proposed smart drugs, such as Ritalin, prescribed for ADHD, have many negative side effects, said Anna-Katharine Brem, co-author of the review, published today in the journal European Neuropsychopharmacology. “Modafinil seems to be the first ‘smart drug’ that is reasonably safe for healthy people.”



She emphasised that although the drug is not thought to be addictive, its long-term effects have not been studied. “It would be difficult to get ethical approval to test the effects of taking this drug in the long term,” she said.



Peter Morgan, at Yale School of Medicine, says there is substantial evidence that other cognitive enhancers, such as caffeine or nicotine, have benefits from short-term use, but that those benefits are erased by long-term use, and are rather replaced by deficiencies in cognitive performance. “There is no evidence that modafinil would be any different in this regard,” he said.



The effects of modafinil on the brain are complex and not well understood. One promising theory is that the drug increases blood flow to brain areas serving attention and learning. It might also enhance brain activity in areas thought to act as “conductors”, which manage skills like memory, reasoning and problem-solving.



“Modafinil is the first real example of a smart drug which can genuinely help, for example, with exam preparation,” said Guy Goodwin, president of the European College of Neuropsychopharmacology. “Previous ethical discussion of such agents has tended to assume extravagant effects before it was clear that there were any. If correct, the present update means the ethical debate is real: how should we classify, condone or condemn a drug that improves human performance in the absence of pre-existing cognitive impairment?”



Goodwin points out that drugs are approved to treat illnesses if they are effective and safe. The manufacturers of modafinil will not attempt to extend the licence to exam doping and there would be no precedent for handling such an application if they did, he said.



“That leaves us in uncharted territory. If there is a demand for modafinil, and people are prepared to pay for it then an illegal market will be created. Whether it becomes a target for political action must depend on how and whether public debate evolves to demand such action.”



Brem and her co-author Ruairidh Battleday think that time for debate has come. “For the first time, we have an agent without serious side effects showing benefits which we haven’t had before.”



“We’re not saying ‘go out and take this drug and your life will be better’,” said Brem. “It is still unlicensed for healthy people - but it is time for a wider debate on how to integrate cognitive enhancement into our lives. We need to explore the ethics, and scientist, politicians and the public need to be involved.”

