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Comment · Thu, February 13, 2014

MDA with a SSRI

Original post in this thread

wolpertinger777 · 12 points

I'm a huge fan of MDA for its psychedelic properties. It has a really special "outrospection" that I have yet to experience in other substances.

The only problem for me is its supposed neurotoxicity because of monoamine release. Would using an SSRI (such as kanna) remove the serotonin releasing properties of the drug and therefore curb the issue of neurotoxicity?

I know that the compound might feel a little different without the serotonin release and the psychedelia might require higher dosages but would it still be effective?

TO SUM UP: Would using an SSRI (such as kanna) with MDA block the serotonin releasing properties and thereby create a non-neurotoxic dopamine/norepinephrine releasing agent with 5ht2a agonism?

What they were answering

Herperderperton · 1 points

That's really interesting, especially the first study. The second study suggests that 5-HT2c antagonism may increase the release, but does not show it is sufficient for it though. You can understand my initial skepticism: when two drugs like MDMA and methamphetamine are closely structurally related and both cause DA and NE release, why implicate a different mechanism for MDMA and one that is shared with non-stimulant psychedelics? It's a shame they didn't directly measure DA levels in the first study. I'd also like to see a highly selective 5-HT2B agonist structurally unrelated to amphetamines tested for serotonin releasing capacity in vivo or in cultured neurons before I'm fully convinced.

u/MisterYouAreSoDumb

Right, it seems that it has to be a multi-receptor mechanism. Simply antagonizing the 5-HT2C receptor is not enough. That is why I thought the 5-HT2A activation, paired with the 5-HT2C inactivation, could be the key.

I'd also like to see a highly selective 5-HT2B agonist structurally unrelated to amphetamines tested for serotonin releasing capacity in vivo or in cultured neurons before I'm fully convinced.

Well look at 6-APB. It's not structurally unrelated to amphetamine. However, it is very selective to 5-HT2B, and causes a much higher release of 5-HT than MDMA. MDMA's affinity for 5-HT2B is 2000nM, where 6-APB is 3.7nM. MDMA's metabolite, MDA, is even more selective than MDMA at 190nM.

http://molpharm.aspetjournals.org/content/63/6/1223.full

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