My friend, I have described completely accurately the way in which SSRI's mitigate depression, and 100% accurately as well the reason why Mirtazepine allows users to roll.
With all due respect, you really didn't. Maybe it was because you tried to explain it too layman but either way it wasn't true.
THAT's why MDMA doesn't make you roll: Your brain just isn't "listening" for any serotonin activity anymore, so it doesn't even know you took any MDMA.
That isn't an accurate layman's explanation. MDMA doesn't make you roll because the SERT is blocked by the binding of the SSRI. So, MDMA comes along and is unable to bind to the reuptake pump for it's reversal and the subsequent serotonin flood. Therefore, much less serotonin is released and the MDMA just floats within the cellular space until being removed as it would usually.
What I don't know is why Mirtazepine is different which you explained below.
Mirtazepine doesn't cause the constant serotonin build up that SSRIs do, it just blocks out certain specific receptors - most of the serotonin receptors are still functioning normally.
What specific receptors? If any of those specific receptors were strongly involved in MDMA's entactogenic effects then it would also block it. If not, then it makes more sense. But your explanation was just general and certainly not 100% accurate.
You have only an issue with the small part of my post talking about down-regulation of serotonergic neurons.
I'm confused, where did you even talk about serotonin down-regulation? The issues I have are two-fold: as mentioned your explanation of SSRI's mechanism of action was tenuous. Secondly:
I mentioned that SSRIs will not give you serotonin syndrome along with MDMA, unless you have just begun taking them recently.
I bolded the important part. There's no empirical support for that and BlueBull provided empirical support suggesting it wouldn't. Have you considered the logic of your post with these two sentences too:
Now, in those studies you posted, do you realize that the patients were treated with 40mg INTRAVENOUS citalopram before their MDMA dose? That is a huge amount - an attack dose, if you will - that is highly unlikely to be representative of normal prescribing habits and therefore patient experience.
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A 10mg dose of citalopram that has been taken for only a few days prior to a huge MDMA dose could easily results in a serotonin syndrome, and this scenario is much more likely to mirror a real life scenario.
The first quote, by using your logic, would be the highest candidate for MDMA & SSRI-induced SS. High dose of SSRI = acute serotonin release + MDMA's massive serotonin release = high risk for SS. But the study didn't report any SS did they? So clearly the theory doesn't work. How would taking 10mg for a few days be all that different from one day of a high dose? I'd argue the other way. One 'attack' dose would be likely to induce a higher acute release than 3 days of 10mg accumulated.
A quick google search shows actually quite a few anecdotal accounts of becoming ill after consuming MDMA on the first few days of an AD drug
Right, but how does that infer SS? I think if you got serotonin syndrome you wouldn't be on the internet writing an anecdote of your experience, you'd be in A&E sweating and chewing your face off, in a perhaps fatal condition. Serotonin syndrome isn't a simple tummy bug after a rave.
To discredit my entire post by saying it is "completely false" is more than a little misleading.
Context is a beautiful thing. Below is BlueBull's post.
you say that you don't roll because your brain doesn't 'listen' for elevated serotonin levels. This is completely false.
It's pretty clear that he didn't discredit your entire post. He said that your explanation for how SSRI's work was completely false and I somewhat agree with him, it was tenuous, but not completely false.
SSRI's will diminish the roll even on the first day, yes, but this does not make serotonin syndrome impossible
It is completely illogical to suggest that SSRI's can both dull a roll and cause SS at the same time. They are like polar opposites of each other. If the SSRI dulled the roll then it reduced the amount of serotonin being released. Whereas for SS to occur, the brain has to be overloaded with uncontrollably high amounts of serotonin. Without using some paradoxical paradigm, how on earth is it possible for those two things to occur simultaneously?
