Evidence for cognitive-enhancing effects of modafinil and methylphenidate is surprisingly thin – perhaps because wakefulness-promotion and cognitive enhancement are confused

Chemical structure of Modafinil.
Chemical structure of Modafinil. (Photo credit: Wikipedia)

There is huge media and other interest in cognitive-enhancing drugs. A few minutes searching on the internet will uncover stories of students and others using modafinil and some other compounds in an effort to enhance their own cognitive function. The evidence for the cognitive-enhancing effects of these compounds is surprisingly thin, however, despite claims about their efficacy. A systematic review of the literature was performed by Dimitris Repantis and colleagues. See the abstract [download here]:

The term neuroenhancement refers to improvement in the cognitive, emotional and motivational functions of healthy individuals through, inter alia, the use of drugs. Of known interventions, psychopharmacology provides readily available options, such as methylphenidate and modafinil. Both drugs are presumed to be in widespread use as cognitive enhancers for non-medical reasons. Based on a systematic review and meta-analysis we show that expectations regarding the effectiveness of these drugs exceed their actual effects, as has been demonstrated in single- or double-blind randomised controlled trials. Only studies with sufficient extractable data were included in the statistical analyses. For methylphenidate an improvement of memory was found, but no consistent evidence for other enhancing effects was uncovered. Modafinil on the other hand, was found to improve attention for well-rested individuals, while maintaining wakefulness, memory and executive functions to a significantly higher degree in sleep deprived individuals than did a placebo. However, repeated doses of modafinil were unable to prevent deterioration of cognitive performance over a longer period of sleep deprivation though maintaining wakefulness and possibly even inducing overconfidence in a person’s own cognitive performance. [bold added]

Any seeming felt-effect might revolve around enhancing expectations of performance – and the mismatch in performance that occurs because of the relative feeling of enhanced performance while you are sleep-deprived with modafinil onboard, compared to coffee or just willpower. There is an intriguing possibility here. In a super paper, Wilhelm Hofmann, Kathleen D. Vohs and Roy F. Baumeister use an experience sampling technique (using smartphones to capture data) to measure what people desire, feel conflicted about, and try to resist in everyday life. One of the remarkable findings in the paper is the frequency with which people report resisting sleep during the course of the day. As the paper states: ‘Perhaps surprisingly, the desire for sleep was frequent throughout the day, rather than concentrated in morning or evening.’ (Abstract below). We seem to want to spend lots of time sleeping, having leisure time, and browsing screens!

Perhaps the apparent experience of cognitive enhancement is merely the feeling of wakefulness promotion experienced by the individual. You study for 40-50 mins – it is tiring, exhausting and depleting to deploy attention, concentration and self-control for such a period of time. With one of these agents on board (or their poor relations – caffeine and nicotine), you can study longer without feeling tired – and mistake the lack of tiredness as enhanced cognition, rather than a baseline shift in levels of arousal that have little to do with cognitive function (and therefore with learning and memory!). You haven’t done much work for your exams – and you can stay awake longer to study for your exams with these compounds on board. And of course you don’t know, or want to know, that the best cognitive enhancers are lots of good quality sleep, engaging in regular aerobic exercise, and distributed practice (a little often, rather than a lot in one go) coupled with regular self-tests; worse, you don’t know that sleep is required for the long-term consolidation of learning and memory. More on these themes again.

Pubmed Abstract

What people desire, feel conflicted about, and try to resist in everyday life.

Psychol Sci. 2012 Jun;23(6):582-8. doi: 10.1177/0956797612437426. Epub 2012 Apr 30.

Booth School of Business, The University of Chicago, Chicago, IL 60637, USA. wilhelm.hofmann@chicagobooth.edu

In the present study, we used experience sampling to measure desires and desire regulation in everyday life. Our analysis included data from 205 adults, who furnished a total of 7,827 reports of their desires over the course of a week. Across various desire domains, results revealed substantial differences in desire frequency and strength, the degree of conflict between desires and other goals, and the likelihood of resisting desire and the success of this resistance. Desires for sleep and sex were experienced most intensively, whereas desires for tobacco and alcohol had the lowest average strength, despite the fact that these substances are thought of as addictive. Desires for leisure and sleep conflicted the most with other goals, and desires for media use and work brought about the most self-control failure. In addition, we observed support for a limited-resource model of self-control employing a novel operationalization of cumulative resource depletion: The frequency and recency of engaging in prior self-control negatively predicted people’s success at resisting subsequent desires on the same day. [emphasis added]

Author: Shane O'Mara


4 thoughts on “Evidence for cognitive-enhancing effects of modafinil and methylphenidate is surprisingly thin – perhaps because wakefulness-promotion and cognitive enhancement are confused

  1. I’m curious if you have any thoughts about nootropics, like piracetam, aniracetam, noopept, etc. Tons of research since the 60’s, and lots of hype right now, but anecdotal reports vary quite dramatically.

    Some believe they are best for people who need some sort of repair – i.e., former substance abusers. Others see them as neuroprotective, and worthwhile to take for long-term brain health. While others use them for specific purposes, like memory, anxiolytic effects, verbal fluency, increased sensory perception, etc.

    I’d love to know your thoughts, considering how knowledgeable you are in the space. Are they not only safe, but protective? Are they potentially good for memory, sensory perception and/or anxiety? Are they perhaps capable of repairing damage? As a scientist, I know you don’t speak in absolutes, but practically speaking: is there something to these substances, or is it all just hype?

    Thank you for your thoughts!

    1. Sorry, Chris, but it’s taken me a while to get back on this one. I’ve been intending to write a much longer piece on neurocognitive enhancement and what we know reliably from randomised control trials (which are the only the only data source we can really rely on). The odd thing looking at the literature is that the centre of action for drug trials is in the area particularly of symptomatic treatment for Alzheimer’s disease, where there is a demonstrable clinical need for cognitive enhancement, and a search for early efficacious treatment. Here there are data showing some compounds do boost cognition (measured by instruments like, e.g., ADAS-COG or whatever). However, I have yet to come across any reports suggesting that donepezil (the gold standard cholinergic modulator) is used for cognitive enhancement by non-Alzheimer’s group for the purposes of cognitive enhancement.

      Taking a stand back and doing a general survey of the literature, it seems to me that in non-pathological groups, the best routes toward cognitive enhancement are actually behavioural/psychological. Regular aerobic exercise (preferably while being exposed to nature – biophilia!) has profoundly positive effects on brain function, as does regular and full nights sleep, then social connectedness and regular cognitive challenges. Finally, there is a little evidence that some form of mindfulness-based meditation (especially mindfulness-based cognitive therapy) is very effective too. All of these have good evidence behind them suggesting they are effective for learning and memory, sensory function and anxiety.

      Regarding neuroprotection and repair, it seems to me still that regular aerobic exercise is probably the best thing currently available, but we also know that the longer you spend in education the great is your level of cognitive reserve (and in turn level of protection against insult). Rates of Alzheimer’s are lower in higher educated populations, all other things being equal.

      So, back to the substances: I continue to be disappointed by how little progress is being made on the drug front, especially where enhancing learning and memory is concerned. There is a huge unmet clinical need for procognitive drugs, and given the pharma disinvestment of the past decade in this area, we are some way from delivering good solutions for patients. However, great strides are being made in behavioural and psychological interventions.

      Please free to email me if you want to discuss things further – shane.omara@gmail.com – given your own work there may be a lot to discuss.

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