Pharmacological Interaction Between Doxazosin and Methylenedioxymethamphetamine (MDMA)

NCT01386177 | Completed Phase 1 DMC

• 1 other identifier: EK 65/11
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mood Disorder; Substance-Related Disorders; Amphetamine-Related Disorders

Keywords

MDMA; doxazosin; norepinephrine; alpha1- receptor; ecstasy; stimulants

Outcome Measures

Primary Outcomes (1)

• Systolic and diastolic blood pressure (mmHg) during 6 hours

  6 hours

Secondary Outcomes (5)

• Subjective effects during 6 hours

  6 hours

• Neuroendocrine plasma levels during 6 hours

  6 hours

• MDMA plasma levels during 6 hours

  6 hours

• Genetic polymorphisms

  assessed after study completion

• Genetic polymorphisms

  assessed after study completion

Other Outcomes (2)

• Prosocial behavior

  5 hours

• Empathy

  5 hours

Study Arms (1)

doxazosin, MDMA, placebo

EXPERIMENTAL

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; Drug: Doxazosin; Drug: placebo

Interventions

3,4-Methylenedioxymethamphetamine DRUG

125 mg per os, single dose

Also known as: MDMA, ecstasy

doxazosin, MDMA, placebo

Doxazosin DRUG

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.

Also known as: Cardura

doxazosin, MDMA, placebo

placebo DRUG

capsules identical to MDMA or doxazosin

doxazosin, MDMA, placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (3)

• 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.

  PMID: 29912955 DERIVED

• 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.

  PMID: 23857311 DERIVED

• 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.

  PMID: 22700038 DERIVED

MeSH Terms

Conditions

Mood Disorders; Substance-Related Disorders; Amphetamine-Related Disorders

Interventions

N-Methyl-3,4-methylenedioxyamphetamine; Doxazosin

Condition Hierarchy (Ancestors)

Mental Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Prazosin; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Matthias E Liechti, MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2011
• First Posted: June 30, 2011
• Study Start: July 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: December 11, 2018

Record last verified: 2018-12

Locations

CH (1)