- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01386177
Pharmacological Interaction Between Doxazosin and Methylenedioxymethamphetamine (MDMA)
December 10, 2018 updated by: University Hospital, Basel, Switzerland
Interactive Effects of Doxazosin and 3,4-Methylenedioxymethamphetamine (MDMA) in Healthy Subjects
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.
Study Overview
Status
Completed
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
16
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Basel, Switzerland, 4031
- University Hospital Basel
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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 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.)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
125 mg per os, single dose
Other Names:
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 Names:
capsules identical to MDMA or doxazosin
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Systolic and diastolic blood pressure (mmHg) during 6 hours
Time Frame: 6 hours
|
6 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Genetic polymorphisms
Time Frame: assessed after study completion
|
Effects of genetic polymorphisms on the response to MDMA
|
assessed after study completion
|
Subjective effects during 6 hours
Time Frame: 6 hours
|
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).)
|
6 hours
|
Neuroendocrine plasma levels during 6 hours
Time Frame: 6 hours
|
neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone
|
6 hours
|
MDMA plasma levels during 6 hours
Time Frame: 6 hours
|
6 hours
|
|
Genetic polymorphisms
Time Frame: assessed after study completion
|
Effects of MDMA on genetic polymorphisms
|
assessed after study completion
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Prosocial behavior
Time Frame: 5 hours
|
Effects on prosociality will be assessed by the Social Value Orientation slide-measurement test.
|
5 hours
|
Empathy
Time Frame: 5 hours
|
Emotional empathy will be assessed by the Multifaceted Empathy Test (MET).
Cognitive empathy will be assessed by Facial Emotion Recognition Tests and the MET.
|
5 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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, Liechti ME. Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex. Psychopharmacology (Berl). 2012 Dec;224(3):363-76. doi: 10.1007/s00213-012-2761-6. Epub 2012 Jun 15.
- Hysek CM, Fink AE, Simmler LD, Donzelli M, Grouzmann E, Liechti ME. alpha(1)-Adrenergic receptors contribute to the acute effects of 3,4-methylenedioxymethamphetamine in humans. J Clin Psychopharmacol. 2013 Oct;33(5):658-66. doi: 10.1097/JCP.0b013e3182979d32.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2011
Primary Completion (Actual)
January 1, 2012
Study Completion (Actual)
January 1, 2012
Study Registration Dates
First Submitted
June 3, 2011
First Submitted That Met QC Criteria
June 29, 2011
First Posted (Estimate)
June 30, 2011
Study Record Updates
Last Update Posted (Actual)
December 11, 2018
Last Update Submitted That Met QC Criteria
December 10, 2018
Last Verified
December 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Pathologic Processes
- Substance-Related Disorders
- Disease
- Mood Disorders
- Amphetamine-Related Disorders
- Physiological Effects of Drugs
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Hallucinogens
- Adrenergic Uptake Inhibitors
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- N-Methyl-3,4-methylenedioxyamphetamine
- Doxazosin
Other Study ID Numbers
- EK 65/11
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Substance-Related Disorders
-
New York State Psychiatric InstituteNational Institute on Drug Abuse (NIDA)CompletedSubstance-Related Disorders | Substance Use | Substance Use Disorders | Substance Abuse | Substance Dependence | Substance Related Problem
-
US Department of Veterans AffairsCompletedAlcoholism | Substance Use Disorders | Substance Abuse | Alcohol Abuse | Substance DependenceUnited States
-
VA Office of Research and DevelopmentRecruiting
-
National Institute on Drug Abuse (NIDA)CompletedSubstance-related Disorders
-
Norwegian University of Science and TechnologyCompletedSubstance-related DisordersNorway
-
University of Southern CaliforniaNational Institute on Drug Abuse (NIDA)Completed
-
University Hospital, Basel, SwitzerlandPsychiatric Hospital of the University of BaselCompleted
-
University of LuebeckFederal Ministry of Health, GermanyCompletedSubstance-related Disorders
-
University of Illinois at Urbana-ChampaignCompletedSubstance-related Disorders
-
University of NebraskaCompletedSubstance-related Disorders | Alcohol-related DisordersUnited States
Clinical Trials on 3,4-Methylenedioxymethamphetamine
-
University Hospital, Basel, SwitzerlandCompleted
-
University Hospital, Basel, SwitzerlandActive, not recruiting
-
VA Loma Linda Health Care SystemMultidisciplinary Association for Psychedelic StudiesRecruitingPost Traumatic Stress Disorder | Combat Stress DisordersUnited States
-
Lykos TherapeuticsNot yet recruitingPharmacokinetics | Hepatic ImpairmentUnited States
-
Lykos TherapeuticsCompleted
-
Brigham and Women's HospitalMclean HospitalTerminatedCancer | Anxiety DisorderUnited States
-
Healing BreakthroughSan Diego Veterans Healthcare System; National Center for PTSD; White River Junction... and other collaboratorsNot yet recruitingPost-Traumatic Stress DisorderUnited States
-
Lykos TherapeuticsNot yet recruitingPsychological Effects of Study Drug
-
Lykos TherapeuticsCompleted
-
Lykos TherapeuticsCompletedPosttraumatic Stress DisorderUnited States