Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review
Abstract
Modafinil is an FDA-approved eugeroic that directly increases cortical catecholamine levels, indirectly upregulates cerebral serotonin, glutamate, orexin, and histamine levels, and indirectly decreases cerebral gamma-amino-butrytic acid levels. In addition to its approved use treating excessive somnolence, modafinil is thought to be used widely off-prescription for cognitive enhancement. However, despite this popularity, there has been little consensus on the extent and nature of the cognitive effects of modafinil in healthy, non-sleep-deprived humans. This problem is compounded by methodological discrepancies within the literature, and reliance on psychometric tests designed to detect cognitive effects in ill rather than healthy populations. In order to provide an up-to-date systematic evaluation that addresses these concerns, we searched MEDLINE with the terms "modafinil" and "cognitive", and reviewed all resultant primary studies in English from January 1990 until December 2014 investigating the cognitive actions of modafinil in healthy non-sleep-deprived humans. We found that whilst most studies employing basic testing paradigms show that modafinil intake enhances executive function, only half show improvements in attention and learning and memory, and a few even report impairments in divergent creative thinking. In contrast, when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning. Importantly, we did not observe any preponderances for side effects or mood changes. Finally, in light of the methodological discrepancies encountered within this literature, we conclude with a series of recommendations on how to optimally detect valid, robust, and consistent effects in healthy populations that should aid future assessment of neuroenhancement.
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A recent systematic review indicates that modafinil has procognitive effects in healthy, non-sleep-deprived individuals.
“A recent systematic review indicates that modafinil has procognitive effects in healthy, non-sleep-deprived individuals [148].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [148]
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- Authors
- Battleday, R. M., & Brem, A.-K.
- Affiliations
- University of Oxford (GB)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Battleday, R.M.
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 25
- Issue
- 11
- Pages
- 1865-1881
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W1180171039
- Semantic Scholar
- 68d8e633d0ddd0bf6915a8dd8fdd9340e0273eed
- Cited by
- 215
- References
- 74
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 14 · 2023: 14 · 2022: 26 · 2021: 25 · 2020: 23 · 2019: 13 · 2018: 24 · 2017: 20 · 2016: 23 · 2015: 9
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroethics, Human Enhancement, Biomedical Innovations
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- modafinil, cognitive enhancement, executive function, attention, learning and memory, off-label drug use, adverse effects, mood effects, methodological discrepancies
- MeSH terms
- Modafinil, Benzhydryl Compounds, Cognition, Humans, Nootropic Agents
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