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MDMA affects the brain by increasing the activity of at least three neurotransmitters the chemical messengers of brain cells : serotonin, 89,90 dopamine, and norepinephrine. MDMA causes greater release of serotonin and norepinephrine than of dopamine. The excess release of serotonin by MDMA likely causes the mood-elevating effects people experience.
However, by releasing large amounts of serotonin, MDMA causes the brain to become ificantly depleted of this important neurotransmitter, contributing to the negative psychological aftereffects that people may experience for several days after taking MDMA. Research in rodents and primates has shown that moderate to high doses of MDMA, given twice daily for four days, damages nerve cells that contain serotonin. For example, 1 to 2 weeks following binge-dosing with MDMA three or four low doses in one dayrats showed decreased expression of the serotonin transporter, 13,97 a protein that allows cells to take up and recycle released serotonin.
The rats also showed changes in the expression of genes that regulate tryptophan hydroxylase, an enzyme involved in serotonin synthesis. Low serotonin is associated with poor memory and depressed mood, 98 thus these findings are consistent with studies in humans that have shown that some people who use MDMA regularly experience confusion, 30 depression, 30,99 anxiety, paranoia, 30, and impairment of memory 83, and attention processes.
Positron emission tomography PET brain imaging studies of people who have stopped using MDMA have shown decreases in brain activity at rest in prefrontal, parietal, and mediotemporal cortices as well as in the amygdala, cingulate, and hippocampus. These are brain regions involved in learning, memory, and emotion formation and processing. It decreased cerebral blood flow in the motor and somatosensory cortex, amygdala, cingulate cortex, insula, and thalamus. These are brain regions involved in emotion formation and processing, behavioral learning, and sensory and motor function.
Additionally, most studies in people do not have behavioral measures from before MDMA use started, making it difficult to rule out pre-existing differences or common underlying risk factors across groups that are separate from MDMA use. National Institutes of Health.
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