Emotional Effects of Methylphenidate and MDMA in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: 3,4-Methylenedioxymethamphetamine; Drug: Methylphenidate; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4000
      • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MDMA, methylphenidate, 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.	Drug: 3,4-Methylenedioxymethamphetamine; 125 mg per os, single dose; Other Names: MDMA; ecstasy; Drug: Methylphenidate; 1 hour before MDMA/placebo 60 mg methylphenidate per os, single dose; Other Names: Concerta; Ritalin; Drug: Placebo; capsules identical to MDMA or methylphenidate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective effect during 24 hours	subjective effects are repetitively assessed by standardized questionnaires.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure (mmHg)during 10 hours		10 hours
Neuroendocrine plasma levels during 10 hours	neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone	10 hours
MDMA plasma levels during 24 hours		24 hours
Heart rate (beats/min)) during 10 hours		10
Emotional and cognitive empathy	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.	5 hours
Prosocial behavior	Effects on prosociality will be assessed by the Social Value Orientation slide-measurement test.	5 hours
Genetic polymorphisms	Effects of genetic polymorphisms on the response to MDMA	assessed after study completion

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• 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.
• Hysek CM, Simmler LD, Schillinger N, Meyer N, Schmid Y, Donzelli M, Grouzmann E, Liechti ME. Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination. Int J Neuropsychopharmacol. 2014 Mar;17(3):371-81. doi: 10.1017/S1461145713001132. Epub 2013 Oct 8.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: October 28, 2011
• First Submitted That Met QC Criteria: November 2, 2011
• First Posted (Estimate): November 6, 2011

Study Record Updates

• Last Update Posted (Estimate): January 21, 2016
• Last Update Submitted That Met QC Criteria: January 20, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: pharmacokinetics; MDMA; pharmacodynamics; emotions; Mechanism of action of MDMA; Interaction study; Effect of MDMA and methylphenidate on emotions
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Hallucinogens; Adrenergic Uptake Inhibitors; Methylphenidate; N-Methyl-3,4-methylenedioxyamphetamine
• Other Study ID Numbers: EK 228/11