Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine: Pharmacodynamics (PD) and Pharmacokinetics (PK)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT00886886
First received: April 22, 2009
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

MDMA releases dopamine, serotonin, and norepinephrine in the brain. Serotonin uptake inhibitors have been shown to interact with 3,4-Methylenedioxymethamphetamine (MDMA) and to decrease its psychoactive and cardiovascular stimulant effects. This finding indicates that MDMA acts in part by releasing serotonin through the serotonin uptake site. However, in vitro studies show that MDMA binds more potently to the norepinephrine uptake site that to the the serotonin or dopamine uptake transporter. In addition, norepinephrine uptake site blockers such antidepressant drugs attenuate some of the behavioral effects of MDMA in animals. These preclinical data indicate that norepinephrine may also contribute to the response to MDMA in humans. To test this hypothesis this study evaluates the interacting effects of the selective norepinephrine transporter inhibitor reboxetine on the subjective and cardiovascular stimulant effects of MDMA in healthy volunteers.


Condition Intervention Phase
Mood Disorder
Substance-related Disorders
Amphetamine-related Disorders
Drug: MDMA
Drug: Reboxetine, 8 mg
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Pharmacological Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy): Pharmacological Effects and Pharmacokinetics

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Effect of reboxetine on subjective responses to MDMA [ Time Frame: 24h ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect of reboxetine on physiological responses to MDMA [ Time Frame: 24h ] [ Designated as safety issue: No ]
  • Effects of reboxetine on pharmacokinetics of MDMA [ Time Frame: 24h ] [ Designated as safety issue: No ]
  • Tolerability of MDMA and reboxetine [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  • Effect of reboxetine on neuroendocrine responses to MDMA [ Time Frame: 24h ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Genetic polymorphisms [ Time Frame: assessed after study completion ] [ Designated as safety issue: No ]
    Effects of genetic polymorphisms on the response to MDMA


Enrollment: 16
Study Start Date: April 2009
Study Completion Date: March 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Reboxetine, MDMA, 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: MDMA
125 mg, single dose
Drug: Reboxetine, 8 mg
two doses 12h and 2h before MDMA
Drug: Placebo
capsules identical to MDMA or Reboxetine

Detailed Description:

The study will use a randomized double-blind cross-over design with four experimental sessions. Reboxetine (8 mg) or placebo will be administered the night before the experimental session and 1 h before the administration of MDMA (125 mg) or placebo to 16 healthy volunteers. Subjective and cardiovascular responses and plasma samples for pharmacokinetics will be repeatedly assessed throughout the experiments.

We hypothesize that the highly selective norepinephrine uptake inhibitor reboxetine will attenuate subjective and especially heart rate and blood pressure responses to MDMA. Such a result would indicate that norepinephrine is critically involved in the pharmacology of MDMA and may provide helpful in the use and development of treatments for Ecstasy intoxications.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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 Tetrahydrocannabinol-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 30 days)
  • Use of medications that are contraindicated or otherwise interfere with the effects of the study medications (monoamine oxidase inhibitors, antidepressants, sedatives etc.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00886886

Locations
Switzerland
University Hospital
Basel, Switzerland
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Matthias E Liechti, MD Department of Internal Medicine, Division of Pharmacology & Toxicology, University Hospital Basel, Switzerland
  More Information

No publications provided by University Hospital, Basel, Switzerland

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT00886886     History of Changes
Other Study ID Numbers: EKBB373/08
Study First Received: April 22, 2009
Last Updated: January 24, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:
MDMA
norepinephrine
Ecstasy
stimulant

Additional relevant MeSH terms:
Amphetamine-Related Disorders
Disease
Mood Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Pathologic Processes
N-Methyl-3,4-methylenedioxyamphetamine
Reboxetine
Adrenergic Agents
Adrenergic Uptake Inhibitors
Antidepressive Agents
Central Nervous System Agents
Hallucinogens
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014