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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3,4-Methylenedioxymethamphetamine | Drug | 125 mg per os, single dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Systolic and diastolic blood pressure (mmHg) during 6 hours | 6 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Subjective effects during 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Prosocial behavior | Effects on prosociality will be assessed by the Social Value Orientation slide-measurement test. | 5 hours |
| Empathy | Emotional empathy will be assessed by the Multifaceted Empathy Test (MET). Cognitive empathy will be assessed by Facial Emotion Recognition Tests and the MET. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthias E Liechti, MD | University Hospital, Basel, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel | Basel | 4031 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29912955 | Derived | 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. | |
| 23857311 | 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. |
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| ID | Term |
|---|---|
| D019964 | Mood Disorders |
| D019966 | Substance-Related Disorders |
| D019969 | Amphetamine-Related Disorders |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
| D064419 | Chemically-Induced Disorders |
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| ID | Term |
|---|---|
| D018817 | N-Methyl-3,4-methylenedioxyamphetamine |
| D017292 | Doxazosin |
| ID | Term |
|---|---|
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 |
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| 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. |
|
|
| placebo | Drug | capsules identical to MDMA or doxazosin |
|
neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone |
| 6 hours |
| MDMA plasma levels during 6 hours | 6 hours |
| Genetic polymorphisms | Effects of MDMA on genetic polymorphisms | assessed after study completion |
| Genetic polymorphisms | Effects of genetic polymorphisms on the response to MDMA | assessed after study completion |
| 5 hours |
| 22700038 | 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. |
| Organic Chemicals |
| D011224 | Prazosin |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |