MDMA related neuro-inflammation and adenosine receptors

Introduction

Kermanian and colleagues introduce MDMA (3,4-methylenedioxymethamphetamine, commonly known as ecstasy) as a widely used recreational psychostimulant with acute psychoactive effects such as euphoria, heightened sociability and sensory sensitivity, but also with significant acute adverse effects including hyperthermia, cardiovascular strain and cognitive disturbances. Earlier research has implicated MDMA in neurotoxic effects on serotonergic and, to a lesser extent, dopaminergic systems in animals and non-human primates, with particular vulnerability reported in limbic and cortical regions such as the hippocampus, amygdala and prefrontal cortex. The authors note that these neurochemical alterations are thought to contribute to memory and learning deficits observed in some human users, although human evidence for persistent serotonergic neurotoxicity remains inconclusive. This review sets out to summarise mechanisms linking MDMA exposure to neuroinflammation and neuronal injury, and to examine the modulatory and potentially protective roles of adenosine receptors (A1, A2A, A2B and A3) in those processes. Kermanian frames the paper around two linked questions: which brain regions and neurotransmitter systems are affected by MDMA, and how might adenosinergic signalling influence MDMA-induced neuroinflammation and addiction-related processes. The authors emphasise the translational interest of adenosine receptors as targets that modulate dopamine, serotonin and glial responses, while flagging unresolved and contradictory findings in the literature.