In summary, this review has provided evidence that the beneficial synergistic effects of MDMA with psychotherapy are attributed, at least in part, to the complex neuropharmacological profile of this entactogen creating a neural setting primed to facilitate new learning and extinguish fear related to traumatic memories. With actions on numerous neurotransmitter and neural pathways, MDMA can theoretically manipulate modulators of emotional learning and memory during psychotherapy in key brain regions, including the amygdala, hippocampus, and prefrontal cortex. Activation of mesocorticolimbic dopaminergic and noradrenergic systems by MDMA can significantly contribute to processes of attention and memory. Future studies using clinically relevant doses can further elucidate the role of MDMA in emotional memory processing, and delineate specific mechanisms of MDMA-assisted psychotherapy for reducing symptoms of PTSD.
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