MDMA serotonergic effects — MRCPsych Paper A MCQ

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ModerateNeurophysiology and neurochemistryMDMA serotonergic effectsMRCPsych Paper A

A 20-year-old student develops euphoria, increased sociability, jaw clenching, sweating and hyponatraemia after taking MDMA and drinking excessive amounts of water. Which pharmacodynamic action most directly produces MDMA's characteristic acute psychoactive effects?

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Correct answer: B — Reversal of serotonin transporter-mediated flux

The best answer is B. MDMA is transported by the serotonin transporter (SERT) and promotes reverse transporter-mediated flux, causing marked serotonin release while also reducing reuptake. This serotonergic action contributes particularly to its entactogenic effects, euphoria and increased sociability; MDMA also affects noradrenaline and dopamine. Jaw clenching and sweating are typical acute adverse effects. Hyponatraemia is associated with excessive hypotonic fluid intake and MDMA-related disturbance of water regulation, rather than being evidence of a different primary receptor mechanism. NMDA receptor antagonism characterises drugs such as ketamine. Acetylcholinesterase inhibition produces a cholinergic syndrome, while H1-receptor activation is not MDMA's principal mechanism. D2-receptor antagonism is characteristic of antipsychotic drugs and would not explain this presentation.

Reference: Sandtner W et al. The external gate of the human and Drosophila serotonin transporters requires a basic/acidic amino acid pair for MDMA translocation and the induction of substrate efflux. Biochemical Pharmacology, 2016. https://pubmed.ncbi.nlm.nih.gov/27638414/