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

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Dolder, Patrick C., Müller, Felix, Schmid, Yasmin, Borgwardt, Stefan J., Liechti, Matthias E.·2018·Psychopharmacology
DOI 10.1007/s00213-017-4650-5PMC PMC5813072
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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.

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  • MDMA at 125 mg increased the subjective experience of being close to others and trusting others by approximately 25% during peak effects.

    “Furthermore, MDMA (125 mg) increased the subjective experience of being close to others and trusting others by approximately 25% during peak effects (10, 39).”

    From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [39]

  • A 125 mg dose of MDMA impaired the identification of fearful faces and, in a second study, of fearful, angry, and sad faces, particularly in women.

    “Additionally, a 125 mg dose of MDMA impaired the identification of fearful faces (39) and of fearful, angry, and sad faces, particularly in women, in a second study (10).”

    From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [39]

  • After the administration of MDMA (125 mg), participants reported increased sexual arousal and desire.

    “After the administration of MDMA (125 mg), participants reported increased sexual arousal and desire (39).”

    From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [39]

  • In contrast to MDMA, methylphenidate and modafinil increased misclassifications of emotions as angry on the FERT while MDMA increased misclassifications as happy.

    “In contrast to MDMA, methylphenidate and modafinil increased misclassifications of emotions as angry on the FERT while MDMA increased misclassifications as happy (39).”

    From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [39]

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Research works printed but not linked: 3

  1. Spielberger CD Gorsuch RC Lusheme RE Manual for the Stait Trait Anxiety Inventory 1970 Palo Alto Consulting Psychologists Press
  2. Vollenweider FX Gamma A Liechti ME Huber T Psychological and cardiovascular effects and short-term sequelae of MDMA (“ecstasy”) in MDMA-naive healthy volunteers Neuropsychopharmacology 1998 19 241 251 10.1038/sj.npp.1395197 9718588 · DOI
  3. Zemishlany Z Aizenberg D Weizman A Subjective effects of MDMA (‘ecstasy’) on human sexual function Eur Psychiatry 2001 16 127 130 10.1016/S0924-9338(01)00550-8 11311178 · DOI

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Authors
Dolder, P. C., Müller, F., Schmid, Y., Borgwardt, S. J., & Liechti, M. E.
Affiliations
University of Basel (CH)
Corresponding author
Liechti, Matthias E.
ORCID
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2017-05-27
Volume
235
Issue
2
Pages
467-479
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
DOI
10.1007/s00213-017-4650-5
PMC
PMC5813072
OpenAlex
W2620385377
Cited by
117
References
85
Citations by year
2026: 3 · 2025: 14 · 2024: 11 · 2023: 15 · 2022: 16 · 2021: 15 · 2020: 15 · 2019: 12 · 2018: 10 · 2017: 6
FWCI
14.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychopharmacology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • edoc (University of Basel) (acceptedVersion)
  • edoc (University of Basel)
Funders
  • Universität Basel (no)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (320030_170249)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroethics, Human Enhancement, Biomedical Innovations
Keywords
MDMA, methylphenidate, modafinil, stimulants, acute drug effects, subjective drug effects, emotional impact, facial emotion recognition, sexual arousal, cortisol, prolactin, oxytocin, pupil dilation, anxiety, sympathomimetic effects, nootropic drugs, healthy volunteers
MeSH terms
Facial Recognition, Modafinil, Adult, Central Nervous System Stimulants, Arousal, Autonomic Nervous System, Double-Blind Method, Emotions, Female, Hallucinogens, Humans, Libido, Male, Methylphenidate, Sexual Behavior, Cross-Over Studies, N-Methyl-3,4-methylenedioxyamphetamine, Young Adult, Healthy Volunteers

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