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Mechanism of action of MDMA (Ecstasy)
| Third-party funded project |
| Project title |
Mechanism of action of MDMA (Ecstasy) |
| Principal Investigator(s) |
Liechti, Matthias Emanuel
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| Organisation / Research unit |
Departement Biomedizin / Clinical Pharmacology (Krähenbühl) |
| Project start |
01.03.2009 |
| Probable end |
31.08.2012 |
| Status |
Completed |
| Abstract |
Our research aims at a better understanding of the mechanism of action of stimulant drugs in particular 3,4-methylenedioxymethamphetamine (MDMA). MDMA is widely used by young people in the form of Ecstasy pills. MDMA is an amphetamine-derivative with strong psychoactive properties. MDMA releases serotonin (5-HT), norepinephrine (NE), and dopamine (DA) from presynaptic terminals. The MDMA-induced release of 5-HT, NE, or DA is thought to be due to reverse-transport of these monoamines through the presynaptic 5-HT, NE, or DA transporter (SERT, NET, or DAT), respectively, resulting in increased concentrations of these monoamines in the synaptic cleft. While the neurochemical effects of MDMA have been relatively well studied in preclinical models, it is less clear how the neurochemistry translates into to the psychotropic and physiological effects in humans. We investigate the mechanism of action and in particular the functional role of NE in the pharmacological and toxic effects of MDMA in vitro and in humans. We characterize how MDMA interacts with the monoamine transporters and how it affects release of monoamines from cells transfected with human SERT, DAT, or NET. In the clinical studies we evaluate the effects of pretreatments with different NE and SERT receptor antagonists on the pharmacodynamics and pharmacokinetics of MDMA in humans using randomized double-blind cross-over/interaction designs in healthy volunteers. Here we explore the clinical mechanism of action of MDMA and which neuroreceptors and neurotransmitters mediate the subjective and cardiovascular effects of MDMA in humans. Together, the in vitro and in vivo studies are aimed at a better understanding of the pharmacology and toxicology of MDMA and related psychostimulants. |
| Financed by |
Swiss National Science Foundation (SNSF)
Foundations and Associations
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10/05/2024
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