Genetic reductions in serotonin transporter may cause some people to respond differently to MDMA

New research suggests that a subgroup of people may respond differently to the drug ecstasy thanks to reductions in a molecule that regulates serotonin signaling between brain cells. The study has been published in the Journal of Psychopharmacology.

“My research group is interested in how genetic and/or early environmental factors shape our brain and behaviour. Particularly as we know that these factors play a crucial role in our susceptibility to psychiatric disorders,” said study author Bart A. Ellenbroek of Victoria University of Wellington and the Behavioural Neurogenetics Group.

“In this study, we investigated to what extent a genetic disruption of the serotonin transporter (a key protein involved in the regulation of the neurotransmitter serotonin) in rats affects the response to MDMA (the active ingredient of ecstasy).”

The serotonin transporter is a protein acts like a vacuum for serotonin, sucking up the neurotransmitter after it has been used for neuronal signaling. Rats that lacked this protein had trouble discriminating between the effects of MDMA and the stimulate amphetamine.

Both MDMA and amphetamine increase levels of dopamine, noradrenaline, and serotonin in the brain. But the findings suggest that MDMA’s effects are much more strongly impacted by serotonin.

The findings also have some implications for humans.

“Genetic reductions in the serotonin transporter are very common in humans (in the Western world about 30% of people have a reduction). Thus our study suggests that humans are likely to respond very differently as well,” Ellenbroek told PsyPost.

“While ecstasy has a relatively low risk of leading to addiction, our study (as well as previous papers from our group) suggest that in these genetically vulnerable rats, ecstasy is much more addictive.”

But the research — like all studies — includes some limitations.

“There are two major caveats. First, the rats have a stronger genetic reduction in the serotonin transporter than humans typically have, and thus we would need to repeat this study with rats with a reduction similar to humans,” Ellenbroek explained.

“Secondly, and most importantly, rats are not small humans, and while the basic pharmacology between rats and humans is quite similar, the translation from animal to human research is notoriously difficult. Thus studies in humans are essential to confirm (or disprove) our claims.”

The study, “A genetic deletion of the serotonin transporter differentially influences the behavioural effects of MDMA”, was authored by Michaela Pettie, Alana Oakly, David N. Harper and Bart A. Ellenbroek.