MDMA vesicular 5-HT depletion and other topics

[JK25]

 

[JK25]

On your original post in that other thread you seemed to use SERT and serotonin interchangeably sometimes - I assumed by the context that you meant serotonin in most cases and that serotonin depletion was the topic, rather than SERT hypoexpression.

SERT expression may not return to 100% normal in some cases in humans, but this could be some sort of compensation rather than a reflection of nerve terminal loss or an issue with synthesizing new SERTs. The same can be said with DAT hypoexpression after amphetamines in humans.

Changes in receptor expression are a different animal as well, as people with mental illness can often show altered receptor expression. That being said, I will say that some former MDMA abusers have upregulation of 5-HT2A in cortex, which could indicate solely decreased pre-synaptic release or maybe loss of some feed-forward excitation that normally would result in increased pre-synaptic release.

In one case, MDMA abusers actually showed about 10% increased dopamine in the putamen with IIRC normal levels elsewhere, but that could just be a typical senstization-to-amphetamine type thing (similar to the persistent locomotor sensitization that animals can show after a single dose of amphetamine).


Just to be clear, I've never argued that former MDMA abusers don't have abnormalities visible with neuroimaging (especially the heavy chronic abusers) and neurocognitive abnormalities, but my main argument was that people aren't having issues 1 year post-MDMA because of a vesicular shortage of serotonin

I'd be happy to read your upcoming post, toodles
CY

Kindly note the illustration here under:

5-HT2 and all of its derivatives are affected very slightly as they are working with the re-absorptional functioning on the other end/ass end of the actively firing synapse, within the post-synaptic cleft vesicle, compared to their neighbors working directly on all MDMA analogues, the 5-HT1 binders and transporters are so directly involved with the actual reception of and distrubution of MDMA throughout the axion's nerve endings taking up full ownership of the axion and then ultimately 5-HT1 releases the MDMA out from within the pre-synaptic cleft into synaptic vesicle and ultimately the actively MDMA and 5-HT1 flooded synapse, now during the peak and flooded with both MDMA and 5-HT1 neurotransmitters through the electro-chemical driven data exchange channels and with nothing to absorb it and nowhere to go they just fucking sit within the synaptic space of 50nanometers more or less, bouncing from one side to the other, round and round, up and down, always turning, fuck me this state is magical.

 

[Cotcha Yankinov]

I'll be honest, I'm still confused as you seem to use many terms interchangeably (are you arguing the SErotonin Reuptake Transporter (SERT) expression doesn't return to normal after MDMA abuse?)

I'm not sure what you mean by "5-HT1 releasing the MDMA out from the pre-synaptic cleft" and such - MDMA is thought to evoke 5-HT release by being a substrate for SERT, after which it then inhibits VMAT, causes reversal of SERT and thus efflux of 5-HT into the synapse.

While there are studies showing 5-HT1B plays a big role in the behavioral effects of MDMA in animals, human studies with ketanserin imply that the 5-HT2A receptor is critical to MDMA response, but my guess is that this likely has very little to do with MDMA binding directly to 5-HT2A.

The R-isomer of MDMA doesn't actually have that high of affinity for 5-HT2A and I would bet that most of the typical MDMA effects are preserved with the S-isomer (which is just more of a releasing agent).

There is the matter of MDA's appreciable direct agonism but once again I think most of the real effects of MDMA are from serotonin release - not direct binding to 5-HT1/5-HT2 or somehow release that is driven by 5-HT1.

If anything 5-HT1 would prevent natural impulse driven transmitter release (normal vesicle fusion) because 5-HT1 act as autoreceptors that impede vesicle fusion, but MDMA's releasing properties work irrespective of autoreceptors specifically because its not acting to increase synaptic 5-HT through normal vesicle-fusion release

 

[JK25]

Oh my soul is this still a thing? Fuck guys since I last posted on this I went through complete chrystal-methamphetamine/MethCathinone/Methylphenidate psychosis. Oh so I lost everything, failed my medical studies and am clinging to life, family wrote me off. It foes suck. So yes, oh yes I wrote pages on this shit and got bored. I'm very into mathematics now, neuro-psychopharmacology was a phase. Let me tell you amphetamine-psychosis was heavy, fun, but I almost killed myself and no way, hmm uhhh. No drug will get between me and the person I love and admire the most on earth, which would be myself. Soooooo cut the crystal kids