New MDMA variants could enable safe psychotherapeutic use

The use of the active ingredient 3,4-methylenedioxy-N-methylamphetamine (MDMA) to support psychotherapy for mental illnesses such as post-traumatic stress disorder is being discussed worldwide — with Australia and New Zealand having approved (and restricted) its controlled use by experts due to possible risks and side effects. Now, an international research team led by the Medical University of Vienna has identified three new variants of MDMA as promising alternatives for safer use in a controlled psychotherapeutic setting, with their research published in the Journal of Neurochemistry.

MDMA has been known as the party drug ‘ecstasy’ since the 1980s, although the first patent for the substance was granted back 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 (tachycardia, high blood pressure, liver and nerve damage) have so far been an obstacle to its widespread therapeutic use. The newly developed MDMA variants (ODMA, TDMA and SeDMA) have been modified in such a way that the positive effects are retained and the negative effects are reduced.

As studies carried out on human cell cultures 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 mood and emotion. In contrast to MDMA, however, the new substances have lower activity at certain serotonin receptors and are also broken down more favourably, resulting in fewer toxic breakdown products.

“This allows the conclusion that both the acute and long-term side effects of ODMA, TDMA and SeDMA may be lower than those of the conventional substance,” said study leader Harald Sitte.

“Since the MDMA analogs 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,” added first author Ana Sofia Alberto-Silva.

Sitte said the new variants’ retention of the therapeutic potential of the conventional substance — while causing fewer side effects — “could advance the controlled use of psychoactive substances in neuropsychiatric illness”. At the same time, he acknowledged the need for further studies to comprehensively test the efficacy and safety of MDMA variants for use in a psychotherapeutic setting, for example in the treatment of post-traumatic stress disorder.

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