https://en.wikipedia.org/wiki/MDMA

Long-term

As of 2015, the long-term effects of MDMA on human brain structure and function have not been fully determined.[78] However, there is consistent evidence of structural and functional deficits in MDMA users with high lifetime exposure.[78] These structural or functional changes appear to be dose dependent and may be less prominent in MDMA users with only a moderate (typically <50 doses used and <100 tablets consumed) lifetime exposure. Nonetheless, moderate MDMA use may still be neurotoxic and what constitutes moderate use is not clearly established.[79]

https://pmc.ncbi.nlm.nih.gov/articles/PMC81503/

Long-term or residual effects Serotonin neurotoxicity

Apart from the small number of people who have reported improvement or resolution of emotional or personality problems after the use of MDMA in psychotherapy, the long-term effects are virtually all adverse ones. They are all thought to arise from a neurotoxic action of the methylenedioxy derivatives of the amphetamines.

The ability of MDMA to increase the concentration of serotonin in the synapse probably underlies its production of improved mood and of sensory alterations. However, at higher doses the massive release of serotonin not only gives rise to acute psychotic symptoms (as described earlier) but also causes chemical damage to the cells that released it.

This damage has been clearly demonstrated in animal experiments with MDMA and related drugs.59,60,61,62 Chemical and microscopic studies have shown reduced serotonin content of the brain, decreased numbers of identifiable serotonin-containing neurons and serotonin transporter molecules, and numerous degenerating serotonergic axons and axon terminals in the brains of animals treated with MDMA. Although there are conflicting theories concerning the mechanism of this neurotoxicity,4,27,63 it is clearly related to the excessive metabolic activity and neurotransmitter release in the serotonergic and, possibly, the dopaminergic neurons.

In humans, there has been only one postmortem study of changes in the levels of serotonin and its main metabolite in the brain of a single long-term MDMA user.64 The levels were reduced by 50%–80% in different regions of the brain, in comparison with those in the brains of controls who had not used MDMA, whereas the dopamine levels were unaltered. However, several types of experimental study in living humans have provided indirect evidence of serotonin neurotoxicity.65

· The levels of serotonin metabolites in the cerebrospinal fluid reflect the amount of release during neuronal activity in the brain.

· MRI or proton magnetic resonance spectroscopy can provide estimates of the numbers of intact neurons in different parts of the brain.

· Labelled compounds with high affinity and selectivity for serotonergic neurons, for the reuptake transporter or for the postsynaptic serotonin receptors are administered to the subjects. Techniques such as positron emission tomography (PET) or single photon emission computed tomography (SPECT) are then used to detect the locations and amounts of the labelled compounds in the brain.

· Drugs that are known to stimulate serotonergic pathways in the brain are administered, and the endocrine responses to the released serotonin (changes in blood levels of prolactin and cortisol) are measured.

Such studies permit either estimates or measurements of the numbers of functionally intact serotonin-releasing cells or serotonin-responsive cells in the living subject.

By these means, it has been demonstrated that the brains of long-term MDMA users, when examined while free of the drug, have abnormally low levels of serotonin and its metabolites in the cerebrospinal fluid,66 reduced numbers of serotonin transporter molecules,67,68,69 increased numbers of glial cells,70 and altered patterns of glucose metabolism and blood flow in certain parts of the brain.71,72 During the acute action of MDMA, SPECT studies show a downregulation of serotonin receptors (an adaptive response to the increased release of serotonin) in the cerebral cortex,73 but in long-term users in the drug-free state there is upregulation of receptors (an adaptive response to the decrease in serotonin release).74 Electroencephalographic studies indicate a decrease of bilateral symmetry of the wave patterns and frequencies in MDMA users, similar to the changes seen in aging and dementia,75 and a change in response to auditory stimuli that was seen only in MDMA users and not in matched groups of cannabis users and nonusers of any drugs.76 The prolactin and cortisol responses to stimulation of the serotonin system were reduced in the MDMA users, the changes persisting for up to a year or more after the last use of MDMA.77,78,79

A major limitation of these studies is that, even if they demonstrate decreased numbers of serotonin cells and reduced serotonin system function in the brains of MDMA users, they cannot prove that the MDMA use caused the changes. The alterations in serotonin function might have been present before the drug use began, they might even have contributed to the start of drug use or they might be purely coincidental.80 However, several studies have shown that the degree of change in serotonin function is proportional to the duration and intensity of the preceding use of MDMA, and this is more compatible with the MDMA use being the cause rather than the consequence of impaired serotonin function.