Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects
This placebo-controlled, double-blind, cross-over study (n=24) compared the acute autonomic, subjective, endocrine, and emotional effects of single doses of MDMA (125 mg), methylphenidate (60 mg), modafinil (600 mg) in healthy subjects using psychometric scales, the Facial Emotion Recognition Task (FERT), and the Sexual Arousal and Desire Inventory (SADI). It found that while all active drugs induced comparable hemodynamic and adverse effects, MDMA induced subjective, emotional, sexual, and endocrine effects that were distinctive from those of methylphenidate and modafinil with the doses used.
Authors
- Yasmin Schmid
- Stefan Borgwardt
- Felix Müller
Published
Abstract
Rationale 3,4-Methylenedioxymethamphetamine (MDMA) is used recreationally and investigated as an adjunct to psychotherapy. Methylphenidate and modafinil are psychostimulants that are used to treat attention-deficit/hyperactivity disorder and narcolepsy, respectively, but they are also misused as cognitive enhancers. Little is known about differences in the acute effects of equally cardiostimulant doses of these stimulant-type substances compared directly within the same subjects.
Methods
We investigated the acute autonomic, subjective, endocrine, and emotional effects of single doses of MDMA (125 mg), methylphenidate (60 mg), modafinil (600 mg), and placebo in a double-blind, cross-over study in 24 healthy participants. Acute drug effects were tested using psychometric scales, the Facial Emotion Recognition Task (FERT), and the Sexual Arousal and Desire Inventory (SADI).
Results
All active drugs produced comparable hemodynamic and adverse effects. MDMA produced greater increases in pupil dilation, subjective good drug effects, drug liking, happiness, trust, well-being, and alterations in consciousness than methylphenidate or modafinil. Only MDMA reduced subjective anxiety and impaired fear recognition and led to misclassifications of emotions as happy on the FERT. On the SADI, only MDMA produced sexual arousal-like effects. Only MDMA produced marked increases in cortisol, prolactin, and oxytocin. In contrast to MDMA, methylphenidate increased subjective anxiety, and methylphenidate and modafinil increased misclassifications of emotions as angry on the FERT. Modafinil had no significant subjective drug effects but significant sympathomimetic and adverse effects.
Conclusions
MDMA induced subjective, emotional, sexual, and endocrine effects that were clearly distinct from those of methylphenidate and modafinil at the doses used.
Research Summary of 'Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects'
Introduction
MDMA (3,4-methylenedioxymethamphetamine) is widely used recreationally and is under investigation as an adjunct to psychotherapy, notably for post-traumatic stress disorder. Methylphenidate and modafinil are clinically used stimulants for attention-deficit/hyperactivity disorder and narcolepsy respectively, but are also misused as cognitive enhancers. The pharmacology of MDMA differs from classical stimulants: MDMA releases serotonin and oxytocin in addition to noradrenaline, whereas methylphenidate and modafinil primarily augment dopaminergic and noradrenergic transmission without strong serotonergic or oxytocinergic effects. Earlier studies indicate MDMA produces prosocial, empathogenic mood changes and endocrine markers of serotonergic activity, but direct within-subject comparisons with other orally administered stimulants have been limited and used only a few outcome measures. Dolder and colleagues designed a double-blind, placebo-controlled, randomized cross-over study to characterise and directly compare the acute autonomic, subjective, emotional, sexual, and endocrine effects of single oral doses of MDMA, methylphenidate, and modafinil in healthy volunteers. The primary a priori hypothesis was that MDMA—but not methylphenidate or modafinil—would produce prosocial/empathic feelings and elevate plasma oxytocin. A secondary aim was to compare methylphenidate and modafinil effects on mood and cognition, complementing prior work in stimulant users.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Dolder, P. C., Müller, F., Schmid, Y., Borgwardt, S. J., & Liechti, M. E. (2018). Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects. Psychopharmacology, 235(2), 467-479. https://doi.org/10.1007/s00213-017-4650-5
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