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

Patrick C Dolder, Felix Müller, Yasmin Schmid, Stefan J Borgwardt, Matthias E Liechti, Patrick C Dolder, Felix Müller, Yasmin Schmid, Stefan J Borgwardt, Matthias E Liechti

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.

Trial registration: ClinicalTrials.gov NCT01951508.

Keywords: Emotion recognition; MDMA; Methylphenidate; Modafinil; Sexual arousal.

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by the Swiss National Science Foundation (grant no. 320030_170249 to MEL and SB) and the University of Basel (to FM).

Figures

Fig. 1
Fig. 1
Autonomic responses to MDMA, methylphenidate, modafinil, and placebo. All active treatments increased systolic and diastolic blood pressure, heart rate, and body temperature. MDMA produced slightly higher increases in blood pressure than methylphenidate and modafinil. However, the overall hemodynamic response, expressed as the rate pressure product, similarly increased after all active treatments compared with placebo. The data are expressed as the mean ± SEM in 24 subjects. The substances were administered at t = 0
Fig. 2
Fig. 2
Subjective effects of MDMA, methylphenidate, modafinil, and placebo on the VASs. MDMA produced greater subjective effect ratings on most VASs compared with methylphenidate and modafinil. MDMA produced greater any drug effects, good drug effects, drug liking, happiness, trust, and feeling close to others than methylphenidate and modafinil. None of the substances produced significant bad drug effects compared with placebo. Modafinil did not produce any significant subjective effects compared with placebo. The data are expressed as the mean ± SEM in 24 subjects. The substances were administered at t = 0
Fig. 3
Fig. 3
On the AMRS, MDMA significantly increased ratings of well-being, emotional excitation, extroversion, and introversion. Methylphenidate and modafinil produced no effects on any of the AMRS scales. On the STAI, MDMA decreased state anxiety, and methylphenidate increased state anxiety. The data are expressed as the mean ± SEM in 24 subjects. The substances were administered at t = 0
Fig. 4
Fig. 4
Endocrine effects of MDMA, methylphenidate, modafinil, and placebo. MDMA increased levels of cortisol, prolactin, and oxytocin compared with placebo. Methylphenidate produced a weak but significant increase in cortisol compared with placebo. Modafinil had no endocrine effects. The data are expressed as the mean ± SEM in 24 subjects. The substances were administered at t = 0
Fig. 5
Fig. 5
On the Facial Emotion Recognition Task, MDMA significantly impaired the recognition of fearful faces compared with placebo. Methylphenidate and modafinil did not significantly alter emotion recognition. The data are expressed as the mean ± SEM in 22 subjects

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Source: PubMed

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