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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methylphenidate, Modafinil, MDMA, Placebo | Other | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylphenidate | Drug | 60mg per os, single dose |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthias E Liechti, MD, MAS | University Hospital, Basel, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel | Basel | Canton of Basel-City | 4000 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29912955 | Derived | 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. | |
| 28551715 | Derived | 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. |
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| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D019964 | Mood Disorders |
| ID | Term |
|---|---|
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D008774 | Methylphenidate |
| D064699 | Dexmethylphenidate Hydrochloride |
| D000077408 | Modafinil |
| D018817 | N-Methyl-3,4-methylenedioxyamphetamine |
| ID | Term |
|---|---|
| D010648 | Phenylacetates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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| Modafinil | Drug | 600mg per os, single dose |
|
|
| MDMA | Drug | 125mg per os, single dose |
|
|
| Placebo | Drug | per os |
|
|
| 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 |
| D010880 |
| Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001559 | Benzhydryl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |