New study finds that MDMA itself causes neurotoxicity

New research confirms that the drug methylenedioxymethamphetamine (MDMA), also known as ecstasy or molly, can result in a set of symptoms known as serotonin syndrome.

The study, published in PLoS One, clears up some confusion about whether MDMA itself or molecular byproducts of the drug are responsible for serotonin syndrome.

PsyPost interviewed Ibrahim M. Shokry and Rui Tao of Florida Atlantic University. Read their explanation of their research below:

PsyPost: Why were you interested in this topic?

Shokry and Tao: 3,4-Methylenedioxymethamphetamine (MDMA) is a psychoactive drug that was synthesized by Merck Pharmaceutical Firm in 1912. Initially, it was used as an adjunct to psychotherapy in the 1970s, and became a popular recreational drug with several street names, including ecstasy in the 1980s. Soon, it was found that the drug causes neurotoxicity and symptoms of physical dysfunction and mental disorder in users clinically known as “serotonin syndrome”. Symptoms include paranoia, memory and sleeping problems, depression, rapid heart rate, elevated body temperature, sweating and dehydration, which can lead to death. MDMA is illegal in most countries, and is a schedule I drug in the USA.

Published research on animals in the 1990s found that direct injection of MDMA in brain cavity failed to produce serotonin syndrome, leading to the suggestion that the neurotoxicity of MDMA is due to its hepatic metabolites, but not to MDMA itself. These results became known on the Internet to some MDMA users who thought that if they take the drug through an injection in the brain, it will keep its euphoric effect without its toxic effects that cause symptoms of serotonin syndrome. This potentially can lead to more problems.

Since we have been studying serotonin syndrome for several years, we found a need to clarify further the relationship between MDMA and serotonin syndrome.

What should the average person take away from your study?

Our results confirm that MDMA itself is psychoactive, and causes neurotoxicity even though its active metabolites can be involved. Moreover, our results explained that direct injection of MDMA in the brain cavity did not cause serotonin syndrome in earlier studies because of poor diffusion and inability to reach its molecular targets in specific brain areas.

Are there any major caveats? What questions still need to be addressed?

No, we believe that this specific question has been thoroughly answered in this investigation.

Is there anything else you would like to add?

Yes, we would like to state that one should be careful in drawing hypotheses, conclusions or suggestions following administration of drugs in the brain cavity. There is a false belief that a drug injected into the brain cavity should produce an intensified effect throughout the brain, assuming that the drug will be distributed to all brain areas in high concentrations.

In our study, we found that following injection of MDMA into the brain (intracranial) and brain cavity (intracerebroventricular injection, ICV), only a localized distribution occurred and a small portion of the brain (hypothalamus and raphe nuclei) could be affected.

In addition to Shokry and Tao, the study “New Insights on Different Response of MDMA-Elicited Serotonin Syndrome to Systemic and Intracranial Administrations in the Rat Brain” was co-authored by John J. Callanan and John Sousa.