Does the ‘smart drug’ modafinil work or not?

  Modafinil is an FDA-approved drug that directly increases cortical catecholamine levels, indirectly upregulates brain 5-HT, glutamate, appetite, and histamine levels, and indirectly decreases brain GABA levels. The drug was originally developed to treat episodic sleepiness, but is now widely used as a “smart drug” to enhance cognitive function, including alertness and attention, which can help with test preparation or other critical situations.  Previous studies in sleep-deprived individuals have shown strong positive effects of modafinil on these cognitive functions, but there is a lack of consensus on the cognitive-enhancing effects of the drug in non-sleep-deprived individuals; in fact, this segment of the population constitutes the majority of current users of the drug. Today, a new systematic review published online in the peer-reviewed journal European Neuropsychopharmacology shows that modafinil does produce positive cognitive effects for non-sleep deprived groups, at least in specific task subsets.  Dr. Ruairidh Battleday of Oxford University and Dr. Anna-Katharine Brem of Harvard Medical School evaluated all research papers addressing cognitive enhancement with modafinil between January 1990 and December 2014. They found 24 studies that explored the benefits associated with taking modafinil, including planning and decision-making, flexibility, learning and memory, and creativity.  Not surprisingly, they found that the cognitive-enhancing effects of modafinil varied by task. The longer the duration and more complex the task, the more consistent the positive effects of modafinil on cognition.  The results showed that modafinil did not significantly improve working memory and thinking flexibility, but it did improve behavioral decision making and planning. Encouragingly, 70% of the studies on the effects of modafinil on mood and side effects suggested a weak overall effect; side effects such as insomnia, headache, stomach pain and nausea were reported in some studies, but these were also present in the placebo group.  According to Dr. Ruairidh Battleday, “This is the first review of the effects of modafinil in non-sleep deprived individuals since 2008, and we were able to include a large amount of recent data. Interestingly, we found that the types of tests used to assess the cognitive effects of modafinil have changed over the past few decades: in contrast to the past, when very basic cognitive tests were developed for individuals with neurological impairment, recent studies have typically used more sophisticated tests. When these tests are used, the cognitive-enhancing effects of modafinil appear to be more conclusive and reliable, especially for “higher-order” brain functions that rely on multiple simple cognitive processes.”  Anna-Katharine Brem, PhD, noted: “So, we came to two main conclusions: first, that modafinil can be considered a cognitive enhancer in a controlled trial setting with few side effects; and second, that we need to find better ways to test normal and even higher-order cognitive function using a more reliable testing. However, we would like to emphasize the ethical considerations: any method used for cognitive enhancement must take this into account, and this is an important direction to explore for future work.”  Commenting on the study, Professor Guy Goodwin, President of the European Neuropsychopharmacology Society (ENCP), said: “This review shows that, based on the current evidence, modafinil enhances cognition independent of its known effects on people with sleep disorders. The authors thus concluded that ‘modafinil deserves the title of the first fully validated smart drug’; in other words, modafinil is a real-life example of a ‘smart drug’ that can truly help individuals with test-preparation needs. In previous ethical discussions about similar drugs, there has been a tendency to exaggerate the effects of drugs until their efficacy, if any, is clearly demonstrated. If this is the case, the current evidence update implies the need for an ethical debate: how should we classify the use of such cognitive enhancement drugs in the absence of cognitive impairment? Should their use be condoned, or condemned?”  ”As the authors point out, modafinil has not been given an indication for use in such cases; nor will it be in the future, as it is already beyond the current competence of regulatory agencies. To date, the non-medical use of mind-altering drugs has conflicted extensively with many socio-professional ethics, and while it has been popular, it has also led to a number of clear harms. Regulation has been problematic and remains so. If the demand for modafinil becomes prominent, it remains to be seen whether social acceptance will rise in response and how the regulatory regime will be established.”  Credit: Systematic review shows ‘smart drug’ modafinil does enhance cognition. media Release: European College of Neuropsychopharmacology (ECNP).

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