[Schatze]

I wasn't being flip with, "what's a neuron here or there". Even if it had any sort of tangible impact, with such minor damage over a long period of time the brain would just rewire itself most likely. Once in a while, go for it. I did, and may in future. The people who show profound malfunction are multiple times per week users who have been doing so continuously for years. I think the alcohol analogy isn't bad, I'll go into it later.

But I've seen the pictures of PET, fMRI, MRI of people who were chronic users. There is a remarkable difference between long term users and controls. There are case studies to back up that in some chronic users this neurological damage does have some sort of psychological or psychiatric consequence. (multiple times per week, higher doses, for years, typically starting young)

There are other individuals who show similar patterns of damage but don't show any psychological or psychiatric effects. Whether plasticity was triggered (and we really don't know why it happens in some individuals more than others) and the brain rewired to compensate, or if there were other neurological changes, or a combination of a bunch of other variables, is still up in the air. Need to wait for enough of them to die and donate their bodies to science.

There is no debate in regards to the neurological damage it does. There is still a debate about the gross effect this neurological damage and its affect on the macro scale because some individuals exhibit major neurological, psychological, psychiatric problems with the pattern of damage to serotonin systems (and these pathologies are consistent with our understanding of what the serotonin pathways do), other people who have similar damage simply do not exhibit any abnormality beyond the neurological level.

Best way to liken it, is to an alcoholic. A drink or two or three or 10 every once in a while won't harm you neurologically to any meaningful extent. But if you look at a long term drunkard, under an MRI his brain has shrivelled, sulci have flattened out, and the ventricles have enlarged. Now, despite this gross neurological damage, some people will never experience measurable defects despite what is blatant and obvious damage that looks very similar on the gross scale as Alzheimers. However, others go on to develop "dry drunk", pre-senile dementia, Wernicke-Korsakoff syndrome (although that's semi-related to diet of an alcoholic as well), etc. etc. Why do some individuals have pervasive neurological damage but suffer no seeming macro scale deficits, and why do others develop dry drunk, pre-senile dementia, anterograde memory, loss of motor and cognitive skills?

We don't know. The damage looks the same, but obviously something is different on the cellular, intracellular, or genetic level. However, there's over a hundred years of research on alcohol, MDMA research was mainly in regards to therapeutic uses, up until around 1985 and then it took some time for these cases of chronic long term users to crop up, and it took a while for imaging to improve. The tentative verdict is that MDMA can cause serious brain damage with chronic, prolonged, frequent use, it's just not guaranteed that it will. Much like alcohol. There may be many underlying diatheses we don't understand in both cases that impact the etiology of developing measurable impairments from both substances.

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off topic aside from one of my courses.
Anecdote: I had to answer a question about the pharmacology of drugs and the neurological changes involved, sometimes seeming contradictory effects that should not occur given the models of neuronal functioning in regards to specific classes of drugs (one of which I included was anti-depressants, for which both the monoamine and serotonin theories of depression these drugs should be absolutely non-functional, didn't get into the emerging 2nd messenger theories that mesh with the other two to make them theoretically work).

There was a subsection after the question that simply asked, "Why is this so surprisingly difficult and seemingly contradictory". My answer, paraphrased; "It's not surprisingly difficult, it would be surprising if it was not difficult to understand the neuronal effects and how they translate into gross behavioural or cognitive functioning. The brain is quite simply the most complex, interconnected singular object that we know of. What would be surprising was if pharmacology and the effects on neurology and the subsequent micro and macro scale manifestations were easy to understand; in a vast system of interconnected, constantly changing neurons and glia of all sorts and varieties (both in cellular activity and makeup and interconnectedness), it would be surprising if many of the results given our current limited, disconnected understanding were not contradictory."

I got full marks for an answer that was supposed to be a lot more technical and lengthy. The above paragraph pretty much encapsulates the problems facing the fields of neurology, psychiatry, and psychology. Neurology and psychology are fairly well understood (not that there isn't IMMENSE room for improvement); psychiatry, somewhat less. It's just the three don't mesh. Which is why this is an interesting field, because attempting to reconcile these fields with each other fully plus a couple of others will be huge. Not just to scientists, but to everyone.