Acute Effects of Methylphenidate, Modafinil, and MDMA on Negative Emotion Processing
André Schmidt, Felix Müller, Patrick C. Dolder, Yasmin Schmid, Davide Zanchi, Laura Egloff, Matthias E. Liechti, Stefan Borgwardt
The International Journal of Neuropsychopharmacology November 22, 2017 DOI: 10.1093/ijnp/pyx112 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 22 |
| Population | Healthy subjects |
| Interventions | Methylphenidate Modafinil 3 4-methylenedioxymethamphetamine |
| Dose | 60 mg methylphenidate, 600 mg modafinil, 125 mg 3,4-methylenedioxymethamphetamine |
| Topics | MDMA |
| Keywords | Modafinil Methylphenidate Dextroamphetamine Dopamine |
| Citations | 25 |
| Key findings | Modafinil increased brain activation in a limbic-cortical-striatal-pallidal-thalamic circuit and amygdala during fearful face processing, and frontal activation correlated with negative mood. |
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.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.