Effects of Methylphenidate, Modafinil, and MDMA on Emotion-processing in Humans: A Pharmaco-fMRI Study

The purpose of this study is to investigate effects of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") on emotion-processing and cognitive performance using functional magnetic resonance imaging (fMRI) techniques. The primary hypothesis is that these psychostimulants differentially affect processing of emotional stimuli and potentially leading to alterations in social cognition and behavior.

Study Overview

• Status: Completed
• Conditions: Healthy; Substance-related Disorder; Mood Disorder
• Intervention / Treatment: Drug: Methylphenidate; Drug: Modafinil; Drug: MDMA; Drug: Placebo

Detailed Description

Methylphenidate and modafinil are increasingly used as performance enhancers or "smart drugs" by students. 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is widely used as recreational drug to enhance emotions. We plan to investigate effects of these psychostimulants on emotion-processing and cognitive performance using functional magnetic resonance imaging (fMRI) techniques. Single doses of methylphenidate (60mg), modafinil (600mg), MDMA (125mg), or placebo will be administered before an fMRI scan in a placebo-controlled, randomized cross-over study design in 24 healthy subjects. Subjective emotional effects, sociability, neurohormonal, cardiovascular responses, and plasma drug concentrations will also be assessed and analyzed for potential brain-induced changes in brain activity in networks processing emotions. The primary hypothesis is that these psychostimulants differentially affect processing of emotional stimuli and potentially leading to alterations in social cognition and behavior. The work should clarify the neuropharmacological basis of the potentially differential effects of these drugs. This information will improve our understanding of the neurofunctional effects of methylphenidate, modafinil, and MDMA, and inform the ongoing debate surrounding brain doping with cognitive and mood enhancers.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4000
      • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 18 and 45 years
• Sufficient understanding of the German language
• Subjects understand the procedures and the risks associated with the study
• Participants must be willing to adhere to the protocol and sign the consent form
• Participants must be willing to refrain from taking illicit psychoactive substances including cannabis during the study
• Participants must be willing to drink only alcohol-free liquids and no xanthine-containing liquids (such as coffee, black or green tea, red bull, chocolate) after midnight of the evening before the study session, as well as during the study day
• Participants must be willing not to drive a traffic vehicle within 24h following MDMA administration
• Women of childbearing potential must have a negative pregnancy test at the beginning of the study and must agree to use an effective form of birth control. Pregnancy tests are repeated before each study session.
• Body mass index: 18-27kg/m2

Exclusion Criteria:

• Chronic or acute medical condition including clinically relevant abnormality in physical exam, laboratory values, or ECG. In particular: Hypertension (>140/90mmgHg) or Hypotension (SBP<85mmHg). Personal or first-grade history of seizures. Cardiac or neurological disorder. This also includes contraindications for MRI scanning (any type of implants such as heart pacer, insulin-pump, cochlea-implants, heart valve)
• Current or previous psychotic or major affective disorder
• Psychotic or major affective disorder in first-degree relatives
• Prior illicit drug use (except tetrahydrocannabinol (THC)-containing products) more than 5 times or any time within the previous 2 months
• Pregnant or nursing women
• Participation in another clinical trial (currently or within the last 30days)
• Use of medications that are contraindicated or otherwise interfere with the effects of the study medications (monoamine oxidase inhibitors, antidepressants, sedatives etc. )
• Tobacco smoking (regularly > 10cigarettes / day)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Methylphenidate, Modafinil, MDMA, Placebo; Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but four treatment conditions in the same subject.	Drug: Methylphenidate; 60mg per os, single dose; Other Names: Concerta; Ritalin; Focalin; Medikinet; Drug: Modafinil; 600mg per os, single dose; Other Names: Modasomil; Drug: MDMA; 125mg per os, single dose; Other Names: Ecstasy; 3,4-Methylenedioxymethamphethamine; Drug: Placebo; per os; Other Names: capsules containing manitol looking identical to methylphenidate, modafinil, and MDMA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on amygdala and striatum BOLD signal responses to emotional stimuli	Functional magnetic resonance (MR) images measuring BOLD (blood oxygen level dependency)activity while subjects will be presented with a series of images of human faces, each showing a fearful or a neutral expression, in an event-related design.	1.5h
Effects on cognitive performance and associated BOLD signal changes in frontal areas	Functional magnetic resonance (MR) images measuring BOLD (blood oxygen level dependency)activity while subjects perform a response inhibition/attention task.	1.5h

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective effects	repeated assessment of subjective effects with validated, standardized questionnaires	7h
Neuroendocrine effects	neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, copeptin	7h
Empathy and social behavior	assessment of cognitive and emotional empathy (empathy is going to be assessed by the Multifaceted Empathy Test (MET)), facial emotion recognition (assessed by the Facial Emotion Recognition Task (FERT)), and prosocial behavior (assessed with the Social Value Orientation Test (SVO)). , as well as of prosocial behaviour	7h
Physiological effects of methylphenidate, modafinil, and MDMA	repeated assessment of blood pressure (mmHg) , heart rate (bpm), body temperature, and pupillary function	7h
Genetic Polymorphisms	Effects of genetic polymorphisms on the response to methylphenidate, modafinil, and MDMA	1 day (assessed once after study completion)
Pharmacokinetics of methylphenidate, modafinil, and MDMA	Time course of plasma concentration, half-life, pharmacokinetic-pharmacodynamic relationship	7h

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Matthias E Liechti, MD, MAS, University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• Vizeli P, Liechti ME. Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects. PLoS One. 2018 Jun 18;13(6):e0199384. doi: 10.1371/journal.pone.0199384. eCollection 2018.
• Dolder PC, Muller F, Schmid Y, Borgwardt SJ, Liechti ME. Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects. Psychopharmacology (Berl). 2018 Feb;235(2):467-479. doi: 10.1007/s00213-017-4650-5. Epub 2017 May 27.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: September 23, 2013
• First Submitted That Met QC Criteria: September 25, 2013
• First Posted (Estimate): September 26, 2013

Study Record Updates

• Last Update Posted (Estimate): January 21, 2016
• Last Update Submitted That Met QC Criteria: January 20, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: social cognition; MDMA; fMRI; Methylphenidate; Modafinil; emotion-processing
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Mood Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Methylphenidate; Modafinil
• Other Study ID Numbers: EK 36/13