The purpose of this study is to determinate the effect of a pre-treatment with the combined serotonin (5-HT) and norepinephrine (NE) transport blocker duloxetine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”). The investigators hypothesize that duloxetine will attenuate the subjective and cardiovascular response to MDMA.
Topic Healthy Subjects
Country Switzerland
Visit trial
Status
Completed
Results Published
Yes
Start date
11 January 2009
End date
05 January 2010
Chance of happening
100%
Phase
Phase I
Design
Blinded
Type
Interventional
Generation
First
Participants
16
Sex
All
Age
18- 45
Therapy
No
Trial Details
3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is widely used by young people for its euphoric effects. MDMA releases serotonin (5-HT), norepinephrine (NE), and dopamine through an interaction with the corresponding presynaptic monoamine uptake transporter. 5-HT transport inhibitors block MDMA-induced 5-HT release in vitro or in animals and also attenuate the subjective and cardiovascular response to MDMA in humans. NE transport inhibitors similarly prevent the MDMA-induced release of NE in cell assays and attenuate behavioral effects of MDMA in animals. Effects of the NE transporter inhibitor reboxetine on the response to MDMA in humans are currently investigated. Here we suggest evaluating effects of pretreatment with the combined 5-HT and NE transport blocker duloxetine on the pharmacodynamics and pharmacokinetics of MDMA. The study will use a randomized double-blind cross-over design with four experimental sessions. Duloxetine (120 mg) or placebo will be administered 16 h and 4 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.NCT Number NCT00990067
Sponsors & Collaborators
University of BaselThe University of Basel Department of Biomedicine hosts the Liechti Lab research group, headed by Matthias Liechti.
Papers
Sex differences in the effects of MDMA (ecstasy) on plasma copeptin in healthy subjectsThis study used a randomized placebo-controlled crossover design to explore the sex differences in increased plasma arginine vasopressin (AVP) secretion following MDMA administration (125mg) in healthy subjects (8 male, 8 female). MDMA significantly elevated plasma copeptin levels at 60 min and at 120 min compared with placebo in women but not in men and MDMA tended to increase urine sodium levels and urine osmolality compared with placebo.
Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex
This study analysed data from five separate clinical trials (n=80) that explored the effects of MDMA on pupillary light reflex and the effects following pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin, respectively. MDMA produced mydriasis, prolonged the latency, reduced the response to light and shortened the recovery time and this impairment returned to normal 6 hours post-treatment. Only reboxetine and duloxetine interacted with the effects of MDMA on pupillary function.