Vienna (OTS) – The use of the active ingredient 3,4-methylenedioxy-N-methylamphetamine (MDMA), commonly known as “ecstasy”, to support psychotherapy for mental illnesses such as post-traumatic stress disorder is being discussed worldwide. While the therapeutic potential of the substance has already been investigated in clinical studies, due to possible risks and side effects, only Australia and New Zealand have so far decided to approve it and use it in a limited, controlled manner by experts. Now, an international research team led by MedUni Vienna has identified three new variants of MDMA as promising alternatives for safer use in psychotherapeutic settings. The results were recently published in the “Journal of Neurochemistry”.
The currently developed MDMA variants (ODMA, TDMA and SeDMA) have been modified by the researchers so that the positive effects are retained and the negative ones are reduced. As the studies on human cell cultures by Harald Sitte’s team from the Center for Physiology and Pharmacology at MedUni Vienna show, the new chemical compounds have a similar effect to MDMA on the relevant clinical target structures in the brain (such as serotonin, dopamine and noradrenaline transporters), which are crucial for regulating moods and emotions. In contrast to MDMA, however, the new substances have lower activity at certain serotonin receptors and are also broken down in such a way that fewer toxic breakdown products are produced: “This allows us to conclude that both the acute and long-term side effects of ODMA, TDMA and SeDMA can be less than those of the conventional substance,” explains study leader Harald Sitte. “Since the MDMA analogues also have a weaker interaction with certain transport proteins in the body that are responsible for the absorption and excretion of drugs, the risk of interactions with other drugs could also be reduced,” adds lead author Ana Sofia Alberto-Silva (Center for Physiology and Pharmacology at MedUni Vienna).
The psychoactive substance MDMA (3,4-methylenedioxy-N-methylamphetamine) has been known as the party drug “ecstasy” since the 1980s – however, the first patent for the substance was granted in 1912. Due to its effect of promoting positive emotions and increasing interpersonal empathy, research in recent years has focused on the potential of MDMA to support psychotherapy for various mental illnesses. However, possible risks and side effects (rapid heartbeat, high blood pressure, liver and nerve damage) have so far represented an obstacle to broad therapeutic use. The MDMA analogues that have been identified so far may provide promising alternatives: “Our experimental results showed that the new variants can retain the therapeutic potential of the conventional substance, but are likely to cause fewer side effects,” says Harald Sitte, summarizing the significance of the results: “This could further advance the controlled use of psychoactive substances in neuropsychiatric disorders.” At the same time, the psychopharmacologist and addiction researcher emphasizes the need for further studies to comprehensively examine the effectiveness and safety of MDMA variants for use in psychotherapeutic settings, for example for the treatment of post-traumatic stress disorders.
Publikation: Journal of Neurochemistry
Bioisosteric analogs of MDMA: Improving the pharmacological profile?
Ana Sofia Alberto-Silva, Selina Hemmer, Hailey A. Bock, Leticia Alves da Silva, Kenneth R. Scott, Nina Kastner, Manan Bhatt, Marco Niello, Kathrin Jäntsch, Oliver Kudlacek, Elena Bossi, Thomas Stockner, Markus R. Meyer, John D. McCorvy, Simon D. Brandt, Pierce Kavanagh, Harald H. Sitte
Two: 10.1111/jnc.16149
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