Emotional Effects of Methylphenidate and MDMA in Healthy Subjects

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: 3,4-Methylenedioxymethamphetamine; Drug: Methylphenidate; Drug: Placebo

• Registration Number: NCT01465685
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

This study compares the interactive emotional/subjective effects of single doses of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and methylphenidate, a dopamine (DA) and norepinephrine (NE) transporter blocker, in healthy subjects. The primary goal is to determine the role of transporter mediated DA and NE release in the subjective response to MDMA in humans. The investigators hypothesize that methylphenidate will attenuate the subjective response to MDMA.

Detailed Description

3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is widely used by young people for its euphoric effects. MDMA releases serotonin (5-HT), dopamine (DA), and norepinephrine (NE). 5-HT release mainly contributes to the subjective effects of MDMA whereas NE release is involved in the cardiovascular and psychostimulant effects of MDMA. DA is also likely to be involved in the rewarding and reinforcing effects of drugs of abuse. However, the functional role of DA in the subjective effects of MDMA in humans is largely unclear. To determine the role of the DA transporter (DAT) in the response to MDMA in humans the investigators test the effects of the DA and NE transporter blocker methylphenidate on the subjective effects of MDMA. The investigators use a randomized double-blind placebo-controlled cross-over design with four experimental sessions. methylphenidate or placebo will be administered before MDMA or placebo to 16 healthy volunteers. Subjective and cardiovascular responses will be repeatedly assessed throughout the experiments and plasma samples are collected for pharmacokinetics. The primary hypothesis is that methylphenidate will significantly reduce the subjective effects of MDMA.

Study Timeline

• Study First Submitted: 2011-10-28
• Study First Submitted QC: 2011-11-02
• Study First Posted: 2011-11-06
• Study Start: 2011-12
• Primary Completion: 2012-12
• Study Completion: 2013-01
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-20
• Last Update Posted: 2016-01-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• 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 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. Subjects must agree not to smoke tobacco for 1 h before and 4 hours after MDMA administration.
• Participants must be willing not to drive a traffic vehicle in the evening of the study day.
• 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: 18-25 kg/m2

Exclusion Criteria

• Chronic or acute medical condition including clinically relevant abnormality in physical exam, laboratory values, or ECG. In particular: Hypertension (>140/90 mmHg). Personal or first-grade history of seizures. Cardiac or neurological disorder.
• Current or previous psychotic or affective disorder
• Psychotic or affective disorder in first-degree relatives
• Prior illicit drug use (except THC-containing (tetrahydrocannabinol) 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 30 days)
• Use of medications that are contraindicated or otherwise interfere with the effects of the study medications (monoamine oxidase inhibitors, antidepressants, sedatives etc.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MDMA, methylphenidate, placebo	3,4-Methylenedioxymethamphetamine	Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two (actually 4) treatment conditions in the same subject.
MDMA, methylphenidate, placebo	Placebo	Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two (actually 4) treatment conditions in the same subject.
MDMA, methylphenidate, placebo	Methylphenidate	Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two (actually 4) treatment conditions in the same subject.

Primary Outcome Measures

Name	Time	Method
Subjective effect during 24 hours	24 hours	subjective effects are repetitively assessed by standardized questionnaires.

Secondary Outcome Measures

Name	Time	Method
Blood pressure (mmHg)during 10 hours	10 hours
Neuroendocrine plasma levels during 10 hours	10 hours	neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone
MDMA plasma levels during 24 hours	24 hours
Heart rate (beats/min)) during 10 hours	10
Emotional and cognitive empathy	5 hours	emotional empathy is going to be assessed by the Multifaceted Empathy Test (MET).; cognitive empathy is going to be assessed by the Facial Emotion Recognition Task and the MET.
Prosocial behavior	5 hours	Effects on prosociality will be assessed by the Social Value Orientation slide-measurement test.
Genetic polymorphisms	assessed after study completion	Effects of genetic polymorphisms on the response to MDMA

Trial Locations

Locations (1)

University Hospital Basel; 🇨🇭 Basel, Basel-Stadt, Switzerland