Authors: Lauren Pulling
Researchers from the University of Liverpool (UK) have conducted a meta-analysis to investigate the effect of ecstasy, or MDMA, on different brain regions. Previous literature has reported mixed observations on the effect of MDMA on serotonin neurons butthis new meta-analysis, published recently in Neuroscience and Biobehavioral Reviews, concludes that serotonin axons with the longest projections from the raphe nuclei may be the most affected.
The team analyzed the findings of seven independent studies that used molecular brain imaging to investigate the effect of ecstasy in regular users compared to polydrug using controls. Previous studies have been limited by small sample sizes, so the meta-analysis permitted the researchers to observe and compare trends in a larger sample. Their overall aim was to observe the effect of MDMA on serotonin transporter (SERT) availability and the downstream effects of this on the serotonin pathway.
MDMA predominantly affects the serotonin pathway, which is involved in the regulation of sleep, emotion, appetite, perception, memory and anxiety.
The team concluded that the behavioral effects of MDMA – including euphoria and increased energy – are mediated by a decrease in SERT activity.
Lead author Carl Roberts (University of Liverpool) commented: “The research team conducted the analysis on seven papers that fitted our inclusion criteria, which provided us with data from 157 ecstasy users and 148 controls. 11 out of the 14 brain regions included in analysis showed SERT reductions in ecstasy users compared to those who took other drugs.”
The team further reported that, in line with preclinical data, an axon’s length has an impact on its vulnerability to the effects of MDMA. Serotonergic neurons with the longest projections – i.e. those that project furthest away from their origin in raphe nuclei, where serotonin is produced – are most susceptible to the neurotoxic effects of MDMA. These longer neurons innervate the cortex, whereas shorter neurons project to subcortical structures.
“The clinical significance of these findings is speculative; however, it is conceivable that the observed effects on serotonin neurons contribute to mood changes associated with ecstasy/MDMA use, as well as other psychobiological changes,” added Roberts. “Furthermore, the observed effects on the serotonin system inferred from the current analysis, may underpin the cognitive deficits observed in ecstasy users.”
Going forward, the researchers suggest that these findings may provide a platform for further research into the long term effects of chronic MDMA use on brain function.
Sources: Roberts C, Jones A, Montgomery C. Meta-analysis of molecular imaging of serotonin transporters in ecstasy/polydrug users. Neurosci. Biobehav. Rev.63 158–167 doi: 10.1016/j.neubiorev.2016.02.003 (2016); University of Liverpool press release.