Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects

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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.

Electronic supplementary material

The online version of this article (doi:10.1007/s00213-017-4650-5) contains supplementary material, which is available to authorized users.

Related collections

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Yasmin Schmid, Florian Enzler, Peter Gasser … (2015)

After no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans.

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Author and article information

Contributors

Matthias E. Liechti: +41 61 328 68 68 , matthias.liechti@usb.ch

Journal

Journal ID (nlm-ta): Psychopharmacology (Berl)

Journal ID (iso-abbrev): Psychopharmacology (Berl.)

Title: Psychopharmacology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0033-3158

ISSN (Electronic): 1432-2072

Publication date (Electronic): 27 May 2017

Publication date PMC-release: 27 May 2017

Publication date (Print): 2018

Volume: 235

Issue: 2

Pages: 467-479

Affiliations

[1 ]GRID grid.410567.1, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, Department of Clinical Research, , University Hospital Basel and University of Basel, ; Schanzenstrasse 55, CH-4056 Basel, Switzerland

[2 ]ISNI 0000 0004 1937 0642, GRID grid.6612.3, Department of Psychiatry (UPK), , University of Basel, ; Basel, Switzerland

Article

Publisher ID: 4650

DOI: 10.1007/s00213-017-4650-5

PMC ID: 5813072

PubMed ID: 28551715

SO-VID: 23b2a00d-28bc-41d8-88bf-6172e94ad330

License:

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.