Modafinil does enhance cognition, review finds

BMJ 2015; 351 doi: (Published 21 August 2015) Cite this as: BMJ 2015;351:h4573
  1. Nigel Hawkes
  1. 1London

A drug developed to treat narcolepsy may be the world’s first safe “smart drug,” say researchers from Oxford and Harvard Universities who have carried out a systematic review of the evidence.1

Modafinil has had a long under-the-counter career among students and academics who claim that it can increase their mental sharpness. As long ago as 2008 the journal Nature invited its readers to own up if they had used cognition enhancing drugs, and one fifth said that they had. Modafinil had been used by 44% of these, who cited improving concentration as the most popular reason.2

The new review, published in European Neuropsychopharmacology,1 showed that they may have been right. Ruairidh Battleday and Anna-Katharine Brem found 24 randomised controlled trials published from 1990 to 2014 that measured the benefits of taking modafinil, including planning and decision making, flexibility, learning and memory, and creativity. Previous studies have shown positive effects in sleep deprived people, but the two scientists included only studies that looked at people with normal sleep patterns.

They reported that the drug made no difference to working memory or flexibility of thought but that it did improve decision making and planning. No real effect on mood was found, and other side effects were slight, but a few people had reported insomnia, headache, stomach ache, or nausea. Patients on placebo also reported the same side effects.

“So we ended up having two main conclusions,” said Brem. “First, that in the face of vanishingly few side effects in these controlled environments, modafinil can be considered a cognitive enhancer; and, second, that we need to figure out better ways of testing normal or even supra-normal cognition in a reliable manner.

“However, we would like to stress the point that, with any method used to enhance cognition, ethical considerations always have to be taken into account: this is an important avenue for future work to explore.”

Battleday commented, “This is the first overview of modafinil’s actions in non-sleep-deprived individuals since 2008, and so we were able to include a lot of recent data. Interestingly, we found that the type of test used to assess modafinil’s cognitive benefits has changed over the last few decades.

“In the past, people were using very basic tests of cognition, developed for neurologically impaired individuals. In contrast, more recent studies have, in general, used more complex tests: when these are used, it appears that modafinil more reliably enhances cognition: in particular, ‘higher’ brain functions that rely on contribution from multiple simple cognitive processes.”

The findings raised ethical issues, said Guy Goodwin, president of the European College of Neuropsychopharmacology, who was not involved in the study. “Previous ethical discussion of such agents has tended to assume extravagant effects before it was clear that there were any,” he said. “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 added, “As the authors point out, modafinil is not licensed for this use, and it will not be because it would be outside the current terms of reference of regulatory bodies. The non-medical use of mind altering drugs has hitherto broadly conflicted with the work ethic of many societies [and] has been very popular but leads to a range of demonstrable harms.

“Regulation has been and remains problematic. We cannot know either if demand for modafinil in the same societies will actually be significant, whether society will be more accepting [or] how regulation will then be framed.”

Modafinil was originally developed in France and was approved in the United Kingdom in 2002. It is now out of patent and produced by a number of generic companies as Provigil.


Cite this as: BMJ 2015;351:h4573


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