Clinical trial NCT01951508: 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
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Healthy
Substance-related Disorder
Mood Disorder
Keywords: Methylphenidate
Modafinil
MDMA
fMRI
emotion-processing
social cognition
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2013-09-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: Effect on amygdala and striatum BOLD signal responses to emotional stimuli
timeFrame: 1.5h
measure: Effects on cognitive performance and associated BOLD signal changes in frontal areas
timeFrame: 1.5h
Secondary outcomes:
measure: Subjective effects
timeFrame: 7h
measure: Neuroendocrine effects
timeFrame: 7h
measure: Empathy and social behavior
timeFrame: 7h
measure: Physiological effects of methylphenidate, modafinil, and MDMA
timeFrame: 7h
measure: Genetic Polymorphisms
timeFrame: 1 day (assessed once after study completion)
measure: Pharmacokinetics of methylphenidate, modafinil, and MDMA
timeFrame: 7h
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel-Stadt
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E Liechti, MD, MAS
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.