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

Early Phase 1
Completed
Conditions
Substance-related Disorder
Healthy
Mood Disorder
Interventions
Registration Number
NCT01951508
Lead Sponsor
University Hospital, Basel, Switzerland
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Methylphenidate, Modafinil, MDMA, PlaceboMDMACross-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.
Methylphenidate, Modafinil, MDMA, PlaceboPlaceboCross-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.
Methylphenidate, Modafinil, MDMA, PlaceboModafinilCross-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.
Methylphenidate, Modafinil, MDMA, PlaceboMethylphenidateCross-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.
Primary Outcome Measures
NameTimeMethod
Effect on amygdala and striatum BOLD signal responses to emotional stimuli1.5h

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.

Effects on cognitive performance and associated BOLD signal changes in frontal areas1.5h

Functional magnetic resonance (MR) images measuring BOLD (blood oxygen level dependency)activity while subjects perform a response inhibition/attention task.

Secondary Outcome Measures
NameTimeMethod
Subjective effects7h

repeated assessment of subjective effects with validated, standardized questionnaires

Pharmacokinetics of methylphenidate, modafinil, and MDMA7h

Time course of plasma concentration, half-life, pharmacokinetic-pharmacodynamic relationship

Physiological effects of methylphenidate, modafinil, and MDMA7h

repeated assessment of blood pressure (mmHg) , heart rate (bpm), body temperature, and pupillary function

Neuroendocrine effects7h

neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, copeptin

Empathy and social behavior7h

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

Genetic Polymorphisms1 day (assessed once after study completion)

Effects of genetic polymorphisms on the response to methylphenidate, modafinil, and MDMA

Trial Locations

Locations (1)

University Hospital Basel

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Basel, Basel-Stadt, Switzerland

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