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Comparative Effects of Methylphenidate, Modafinil, and MDMA on Response Inhibition Neural Networks in Healthy Subjects.

ABSTRACT: Psychostimulants such as methylphenidate and modafinil are increasingly used by healthy people for cognitive enhancement purposes, whereas the acute effect of 3,4-methylenedioxymethamphetamine (ecstasy) on cognitive functioning in healthy subjects remains unclear. This study directly compared the acute effects of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine on the neural mechanisms underlying response inhibition in healthy subjects.Using a double-blind, within-subject, placebo-controlled, cross-over design, methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine were administrated to 21 healthy subjects while performing a go/no-go event-related functional magnetic resonance imaging task to assess brain activation during motor response inhibition.Relative to placebo, methylphenidate and modafinil but not 3,4-methylenedioxymethamphetamine improved inhibitory performance. Methylphenidate significantly increased activation in the right middle frontal gyrus, middle/superior temporal gyrus, inferior parietal lobule, presupplementary motor area, and anterior cingulate cortex compared with placebo. Methylphenidate also induced significantly higher activation in the anterior cingulate cortex and presupplementary motor area and relative to modafinil. Relative to placebo, modafinil significantly increased activation in the right middle frontal gyrus and superior/inferior parietal lobule, while 3,4-methylenedioxymethamphetamine significantly increased activation in the right middle/inferior frontal gyrus and superior parietal lobule.Direct comparison of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine revealed broad recruitment of fronto-parietal regions but specific effects of methylphenidate on middle/superior temporal gyrus, anterior cingulate cortex, and presupplementary motor area activation, suggesting dissociable modulations of response inhibition networks and potentially the superiority of methylphenidate in the enhancement of cognitive performance in healthy subjects.

SUBMITTER: Schmidt A

PROVIDER: S-EPMC5581485 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Comparative Effects of Methylphenidate, Modafinil, and MDMA on Response Inhibition Neural Networks in Healthy Subjects.

Schmidt André A Müller Felix F Dolder Patrick C PC Schmid Yasmin Y Zanchi Davide D Liechti Matthias E ME Borgwardt Stefan S

The international journal of neuropsychopharmacology 20170901 9

<h4>Background</h4>Psychostimulants such as methylphenidate and modafinil are increasingly used by healthy people for cognitive enhancement purposes, whereas the acute effect of 3,4-methylenedioxymethamphetamine (ecstasy) on cognitive functioning in healthy subjects remains unclear. This study directly compared the acute effects of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine on the neural mechanisms underlying response inhibition in healthy subjects.<h4>Methods</h4>Using a ...[more]

PMID: 28525569

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Project description:Lysergic acid diethylamide (LSD) is a classic psychedelic, 3,4-methylenedioxymethamphetamine (MDMA) is an empathogen, and D-amphetamine is a classic stimulant. All three substances are used recreationally. LSD and MDMA are being investigated as medications to assist psychotherapy, and D-amphetamine is used for the treatment of attention-deficit/hyperactivity disorder. All three substances induce distinct acute subjective effects. However, differences in acute responses to these prototypical psychoactive substances have not been characterized in a controlled study. We investigated the acute autonomic, subjective, and endocrine effects of single doses of LSD (0.1 mg), MDMA (125 mg), D-amphetamine (40 mg), and placebo in a randomized, double-blind, cross-over study in 28 healthy subjects. All of the substances produced comparable increases in hemodynamic effects, body temperature, and pupil size, indicating equivalent autonomic responses at the doses used. LSD and MDMA increased heart rate more than D-amphetamine, and D-amphetamine increased blood pressure more than LSD and MDMA. LSD induced significantly higher ratings on the 5 Dimensions of Altered States of Consciousness scale and Mystical Experience Questionnaire than MDMA and D-amphetamine. LSD also produced greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity than MDMA and D-amphetamine. LSD also induced greater impairments in subjective ratings of concentration, sense of time, and speed of thinking compared with MDMA and D-amphetamine. MDMA produced greater ratings of good drug effects, liking, high, and ego dissolution compared with D-amphetamine. D-Amphetamine increased ratings of activity and concentration compared with LSD. MDMA but not LSD or D-amphetamine increased plasma concentrations of oxytocin. None of the substances altered plasma concentrations of brain-derived neurotrophic factor. These results indicate clearly distinct acute effects of LSD, MDMA, and D-amphetamine and may assist the dose-finding in substance-assisted psychotherapy research.

Dataset Information

Comparative Effects of Methylphenidate, Modafinil, and MDMA on Response Inhibition Neural Networks in Healthy Subjects.

Publications

Comparative Effects of Methylphenidate, Modafinil, and MDMA on Response Inhibition Neural Networks in Healthy Subjects.

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