Stereoselective, sex-dependent 5-HT2A receptor modulation of cortical plasticity by MDMA in mice.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology February 2, 2026 Maya C Gaines-Smith, Justin M Silverman, Michael Fiorillo et al. 3 citations
The drug MDMA, also known as ecstasy, is being studied as a possible aid in psychotherapy for hard-to-treat mental health conditions, but how it works in the brain is not fully understood. In experiments with mice, the S(+) form of MDMA, but not the R(-) form, activated a specific serotonin receptor (5-HT2AR) and caused changes in brain cell connections in the frontal cortex of males. The R(-) form had little effect except for a head-twitch response in females. Blocking the serotonin transporter with fluoxetine prevented these effects, showing that MDMA works indirectly by increasing serotonin levels. These results reveal that MDMA's effects on brain plasticity depend on both the drug's chemical form and the sex of the animal.