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

Primary Purpose

Healthy, Substance-related Disorder, Mood Disorder

Status
Completed
Phase
Early Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
Methylphenidate
Modafinil
MDMA
Placebo
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Healthy focused on measuring Methylphenidate, Modafinil, MDMA, fMRI, emotion-processing, social cognition

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • University Hospital Basel

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Methylphenidate, Modafinil, MDMA, Placebo

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Subjective effects
repeated assessment of subjective effects with validated, standardized questionnaires
Neuroendocrine effects
neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, copeptin
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
Physiological effects of methylphenidate, modafinil, and MDMA
repeated assessment of blood pressure (mmHg) , heart rate (bpm), body temperature, and pupillary function
Genetic Polymorphisms
Effects of genetic polymorphisms on the response to methylphenidate, modafinil, and MDMA
Pharmacokinetics of methylphenidate, modafinil, and MDMA
Time course of plasma concentration, half-life, pharmacokinetic-pharmacodynamic relationship

Full Information

First Posted
September 23, 2013
Last Updated
January 20, 2016
Sponsor
University Hospital, Basel, Switzerland
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1. Study Identification

Unique Protocol Identification Number
NCT01951508
Brief Title
Effects of Methylphenidate, Modafinil, and MDMA on Emotion-processing in Humans: A Pharmaco-fMRI Study
Official Title
Effects of Methylphenidate, Modafinil, and MDMA on Emotion-processing in Humans: A Pharmaco-fMRI Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Substance-related Disorder, Mood Disorder
Keywords
Methylphenidate, Modafinil, MDMA, fMRI, emotion-processing, social cognition

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methylphenidate, Modafinil, MDMA, Placebo
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Methylphenidate
Other Intervention Name(s)
Ritalin, Concerta, Medikinet, Focalin
Intervention Description
60mg per os, single dose
Intervention Type
Drug
Intervention Name(s)
Modafinil
Other Intervention Name(s)
Modasomil
Intervention Description
600mg per os, single dose
Intervention Type
Drug
Intervention Name(s)
MDMA
Other Intervention Name(s)
3,4-Methylenedioxymethamphethamine, Ecstasy
Intervention Description
125mg per os, single dose
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
capsules containing manitol looking identical to methylphenidate, modafinil, and MDMA
Intervention Description
per os
Primary Outcome Measure Information:
Title
Effect on amygdala and striatum BOLD signal responses to emotional stimuli
Description
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.
Time Frame
1.5h
Title
Effects on cognitive performance and associated BOLD signal changes in frontal areas
Description
Functional magnetic resonance (MR) images measuring BOLD (blood oxygen level dependency)activity while subjects perform a response inhibition/attention task.
Time Frame
1.5h
Secondary Outcome Measure Information:
Title
Subjective effects
Description
repeated assessment of subjective effects with validated, standardized questionnaires
Time Frame
7h
Title
Neuroendocrine effects
Description
neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, copeptin
Time Frame
7h
Title
Empathy and social behavior
Description
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
Time Frame
7h
Title
Physiological effects of methylphenidate, modafinil, and MDMA
Description
repeated assessment of blood pressure (mmHg) , heart rate (bpm), body temperature, and pupillary function
Time Frame
7h
Title
Genetic Polymorphisms
Description
Effects of genetic polymorphisms on the response to methylphenidate, modafinil, and MDMA
Time Frame
1 day (assessed once after study completion)
Title
Pharmacokinetics of methylphenidate, modafinil, and MDMA
Description
Time course of plasma concentration, half-life, pharmacokinetic-pharmacodynamic relationship
Time Frame
7h

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthias E Liechti, MD, MAS
Organizational Affiliation
University Hospital, Basel, Switzerland
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Basel
City
Basel
State/Province
Basel-Stadt
ZIP/Postal Code
4000
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
29912955
Citation
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.
Results Reference
derived
PubMed Identifier
28551715
Citation
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.
Results Reference
derived

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

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