No cross tolerance MDMA/MDA. Why?

[Beta]

It’s known that MDMA and MDA have no cross tolerance. In the other hand, MDMA tolerance comes from serotonin depletion and receptors down regulation.
Even if it acts differently, I thought that MDA also act on serotonin.
Is it right?
If yes, why MDA and MDMA don't exhibit cross tolerance then?
Cheers

[Beta]

Nobody has a clue?

[Bezzz]

swims not heard of this one. Do you have any writings on this as it sounds like an interesting point? You say it's known, but it would be good to know where swiy heard it.

[Beta]

Here are some links:
http://www.mdma.net/mdma/cross-tolerance.html
http://www.drugs-forum.com/forum/sho...84&postcount=1

[KyleM]

This is purely speculation based on what SWIM knows about each drug and is should not be considered completely factual until more studies are done, but...

There most likely is some cross-tolerance to some degree. Both will stimulate the release of serotonin. If what Shulgin is implying is correct, then MDMA will have more affinity and and is more effective at the serotonin reuptake transporter sites (SERT), meaning MDMA will cause a much greater release of serotonin and prevent a greater amount of serotonin from being removed from the synapse via the SERT. It is known that MDMA also has weak affinity for 5-HT2A receptors, whereas MDA has a greater affinity. So to SWIM the senario seems like this: MDMA is releasing alot of serotonin via SERT, which then binds to receptors which in turn stimulates dopamine/oxytocin, with possible minor psychedelic effects resulting from MDMA's direct binding to the serotonin receptors. With MDA it seems that it most likely had lower affinity/effectiveness for the SERT, causing a much lower release of serotonin as well as oxytocin/dopamine induced by serotonin, while not preventing as much from being removed from the synapse via SERT. With MDA's higher 5-HT2A affinity than MDMA, a more significant psychedelic effect is possible, and possibly a greater release of dopamine via 5-HT2A binding from a combination of MDA and serotonin binding to the receptors.

So MDMA is completely dependent on SERT for it to work and will cause more tolerance related to serotonin depletion/receptor desensitization and oxytocin/dopamine receptor desensitization. With serotonin depletion, less dopamine will be able to be released by serotonin receptors. In this case MDA could theoretically still produce effects by acting directly on receptors. It seems eventually both, if used excessively would lead to depletions and desensitizations of some sort and ultimately result in cross tolerance to much of the effects (not all), but immediate cross-tolerance as seen with psilocin and LSD is unlikely to occur the same way.

[Beta]

Thank you KyleM.