Pharmacological Interaction Between Doxazosin and Methylenedioxymethamphetamine (MDMA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT01386177
First received: June 3, 2011
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to determinate the effect of a pre-treatment with doxazosin, a alpha1-adrenergic receptor blocker, on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). The investigators hypothesize that doxazosin will attenuate the cardiovascular and subjective response to MDMA.


Condition Intervention Phase
Mood Disorder
Substance-Related Disorders
Amphetamine-Related Disorders
Drug: 3,4-Methylenedioxymethamphetamine
Drug: Doxazosin
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Interactive Effects of Doxazosin and 3,4-Methylenedioxymethamphetamine (MDMA) in Healthy Subjects

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Systolic and diastolic blood pressure (mmHg) during 6 hours [ Time Frame: 6 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Subjective effects during 6 hours [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    subjective effects are going to be assessed by various standardized questionnaires (e.g. visual analogue scales (VAS), the 5 dimension Altered State of consciousness questionnaire, or the adjective mood rating scale (AMRS).)

  • Neuroendocrine plasma levels during 6 hours [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone

  • MDMA plasma levels during 6 hours [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Genetic polymorphisms [ Time Frame: assessed after study completion ] [ Designated as safety issue: No ]
    Effects of MDMA on genetic polymorphisms

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


Other Outcome Measures:
  • Prosocial behavior [ Time Frame: 5 hours ] [ Designated as safety issue: No ]
    Effects on prosociality will be assessed by the Social Value Orientation slide-measurement test.

  • Empathy [ Time Frame: 5 hours ] [ Designated as safety issue: No ]
    Emotional empathy will be assessed by the Multifaceted Empathy Test (MET). Cognitive empathy will be assessed by Facial Emotion Recognition Tests and the MET.


Enrollment: 16
Study Start Date: July 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: doxazosin, 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: 3,4-Methylenedioxymethamphetamine
125 mg per os, single dose
Other Names:
  • MDMA
  • ecstasy
Drug: Doxazosin

3 days (-64h) before MDMA: 4 mg doxazosin per os. 2 days (-40h) before MDMA: 8 mg doxazosin per os.

1 day (-16h) before MDMA: 8 mg doxazosin per os.

Other Name: Cardura
Drug: placebo
capsules identical to MDMA or doxazosin

Detailed Description:

3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is widely used by young people for its euphoric effects. MDMA releases serotonin (5-HT), dopamine, and norepinephrine (NE). NE release is thought to mediate the cardiovascular effects of MDMA and may also contribute to its psychostimulant effects. However, the functional role of adrenergic postsynaptic receptors in the cardiovascular and subjective effects of MDMA in humans is largely unclear. To determine the role of alpha-adrenergic receptors in the response to MDMA in humans the investigators test the effects of the alpha1-receptor blocker doxazosin on the physiological and subjective effects of MDMA. The investigators use a randomized double-blind placebo-controlled cross-over design with four experimental sessions. doxazosin 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 doxazosin will significantly reduce the blood pressure response to MDMA.

  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: NCT01386177

Locations
Switzerland
University Hospital Basel
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Matthias E Liechti, MD 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: NCT01386177     History of Changes
Other Study ID Numbers: EK 65/11
Study First Received: June 3, 2011
Last Updated: January 24, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:
MDMA
doxazosin
norepinephrine
alpha1- receptor
ecstasy
stimulants

Additional relevant MeSH terms:
Amphetamine-Related Disorders
Substance-Related Disorders
Mood Disorders
Mental Disorders
Doxazosin
N-Methyl-3,4-methylenedioxyamphetamine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hallucinogens
Central Nervous System Agents
Psychotropic Drugs
Serotonin Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014