Acute effects of methylphenidate, modafinil and MDMA on negative emotion processing
This double-blind, placebo-controlled study (n=22) only used MDMA as a control condition and found that modafinil, although often used as a cognitive enhancer, may show some adverse effects regarding emotion processing.
Authors
- Yasmin Schmid
- Stefan Borgwardt
- Felix Müller
Published
Abstract
Background
Stimulants such as methylphenidate and modafinil are frequently used as cognitive enhancers in healthy people, whereas 3,4-methylenedioxymethamphetamine (ecstasy) is proposed to enhance mood and empathy in healthy subjects. However, comparative data on the effects of methylphenidate and modafinil on negative emotions in healthy subjects have been partially missing. The aim of this study was to compare the acute effects of methylphenidate and modafinil on the neural correlates of fearful face processing using 3,4-methylenedioxymethamphetamine as a positive control.
Methods
Using a double-blind, within-subject, placebo-controlled, cross-over design, 60 mg methylphenidate, 600 mg modafinil, and 125 mg 3,4-methylenedioxymethamphetamine were administrated to 22 healthy subjects while performing an event-related fMRI task to assess brain activation in response to fearful faces. Negative mood states were assessed with the State-Trait Anxiety Inventory and subjective ratings.
Results
Relative to placebo, modafinil, but not methylphenidate or 3,4-methylenedioxymethamphetamine, increased brain activation within a limbic-cortical-striatal-pallidal-thalamic circuit during fearful face processing. Modafinil but not methylphenidate also increased amygdala responses to fearful faces compared with 3,4-methylenedioxymethamphetamine. Furthermore, activation in the middle and inferior frontal gyrus in response to fearful faces correlated positively with subjective feelings of fearfulness and depressiveness after modafinil administration.
Conclusions
Despite the cognitive enhancement effects of 600 mg modafinil in healthy people, potential adverse effects on emotion processing should be considered.
Research Summary of 'Acute effects of methylphenidate, modafinil and MDMA on negative emotion processing'
Introduction
Methylphenidate (MPH) and modafinil are stimulants prescribed for attention-deficit hyperactivity disorder and narcolepsy, respectively, but are also used as cognitive enhancers by healthy people. The authors note that while their cognitive effects have been investigated, less is known about how these drugs modulate negative emotion processing, an important consideration because alterations in processing of negative facial expressions—particularly fearful faces—have been linked to anxiety and mood disorders and are mediated by regions such as the amygdala. Schmidt and colleagues therefore set out to compare the acute effects of a single dose of MPH (60 mg) and modafinil (600 mg) on neural responses to fearful faces in healthy volunteers, using 125 mg MDMA as a positive control because of its established mood-enhancing and prosocial effects. The primary hypothesis was that MPH and modafinil would increase amygdala responses to fearful faces relative to MDMA and placebo, and that such neural effects would relate to changes in negative mood states (state-anxiety, fearfulness, depressiveness). This within-subject, placebo-controlled, crossover fMRI study aimed to detect potential adverse effects on emotion processing despite the drugs' cognitive-enhancing properties.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Schmidt, A., Müller, F., Dolder, P. C., Schmid, Y., Zanchi, D., Egloff, L., Liechti, M. E., & Borgwardt, S. (2018). Acute effects of methylphenidate, modafinil and MDMA on negative emotion processing. International Journal of Neuropsychopharmacology, 21(4), 345-354. https://doi.org/10.1093/ijnp/pyx112
References (7)
Papers cited by this study that are also in Blossom
Bedi, G., Hyman, D., De Wit, H. · Biological Psychiatry (2010)
Bershad, A. K., Miller, M. A., Baggot, M. J. et al. · Journal of Psychopharmacology (2016)
Dolder, P. C., Müller, F., Schmid, Y. et al. · Psychopharmacology (2017)
´dric, C., Hysek, M., Schmid, Y. et al. · Social Cognitive and Affective Neuroscience (2013)
Kirkpatrick, M. G., Delton, A. W., de Wit, H. et al. · Journal of Psychopharmacology (2015)
Kuypers, K. P. C., Dolder, P. C., Ramaekers, J. G. et al. · Journal of Psychopharmacology (2017)
Mueller, F., Lenz, C., Dolder, P. C. et al. · Translational Psychiatry (2017)
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Ramaekers, J. G., Kuypers, K. P. C., Vollenweider, F. X. · Molecular Psychiatry (2026)
Ertl, N., Ashraf, I., Azizi, L. et al. · Biorxiv (2025)
Chaliha, D., Mamo, J. C., Albrecht, M. et al. · Current Neuropharmacology (2021)
Van Hedger, K., Mayo, L. M., Bershad, A. K. et al. · Current Addiction Reports (2021)
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