Stimulants Explain DAT: Why Is Wellbutrin Inhibiting Amphetamines?

[m060mm]

Adding a D(A)RI/NRI to amphetamines should potentiate both of them, right?

That was my doctor's logic. And on a basic level, it makes sense. It clearly works for some people. Not me.

Theory 1: One member said that the inhibition of DAT by Wellbutrin would prevent the amphetamines from exerting their relatively more potent action. They say amphetamines are primarily D(A)RIs at low/therapeutic doses but my understanding is that they reverse the direction of DAT.

If amphetamines reverse DAT and Wellbutrin immobilizes the transporters (or otherwise affects the reversal negatively) then that makes sense - Wellbutrin locks amphetamine out.

Theory 2:Amphetamines also increase dopamine concentrations in the cytosol of pre-synaptic vesicles. So when our behavior/environment triggers release, we release more into the synapse?

This leads to generalizations that our bodies downregulate DA production or release as a result of elevated average synaptic concentrations via Wellbutrin. Could it be tolerance?

Finally, Wellbutrin inhibits 2D6! Shouldn't this shift the whole AUC up?

 

[_Synapse]

it very well could inhibit... i would not recommend dosing both unless prescribed... or as prescribed... don't mess with the antidepressants ssri, snri, etc.

anyway i took mdma on citalopram and i thought maybe it was responsible for dampening the effects but it was only my guess... or a massive cross tolerance to amphetamines that somehow transfered over to the methylenedioxy groups which I'm sure is possible but I got almost 0 effects... so either I'm special and all my friends who took it are liars or bitches and it was not even mdma which is possible... they said it fucked them up though all of them every single one... thats a different story... but it is possible your SNRI is inhibiting your amphetamines but I'm sure its only to some extent.. you could (dangerously) break through that, though I would not at all. get off the wellbutrin if you want to use or abuse any amphetamine drugs safely... safely meaning without some fucked up combination effects or some kind of serotonin syndrome, though thats not likely but something along those lines with comboing snri's with massive dopamine and norepinephrine reuptake inhibiting drugs i.e. amphetamines... just would to stay safer, I would always be worried about that but that is just me. I tend to worry or get scared in taking antidepressants with speed of all types in non therapeutical doses...

For most people for add the doc usually gives stims or the wellbutrin antidepressants or shit like guanfacine... I would not mix the first two though if its higher than normal amphetamine doses. like i said thats just me though... too much to go wrong with the unexpected shit the antidepressants (all types) can cause... especially in combining them with stuff that plays with the same neurotransmitter reuptake processes...

i could be wrong completely I do not know....


edit: yes it very well could be tolerance... my tolerance to amphetamines has been a major concern before I knew why my drugs were not working... "I was like wtf am I dying? Did I fuck myself up? but my heart rate is normal" *checks pulse every 5 minutes* lol haha. oh how the stimulants have a major cause for paranoia too fuckin blows.

 

[m060mm]

Speaking of multiple drugs working on the same system(s), isn't MDMA contraindicated with SSRI's? Serotonin syndrome. I've read that SSRI's stop you from rolling too.


I wrote it wrong initially - Wellbutrin is a DRI/NRI - no 'S', no serotonin.

My amphetamine use has been pretty reasonable and sporadic - especially lately. I don't have an inherent tolerance at this point; I'm curious if the Wellbutrin created a tolerance via prolonged DA/NE exposure.

 

[_Synapse]

Speaking of multiple drugs working on the same system(s), isn't MDMA contraindicated with SSRI's? Serotonin syndrome. I've read that SSRI's stop you from rolling too.


I wrote it wrong initially - Wellbutrin is a DRI/NRI - no 'S', no serotonin.

My amphetamine use has been pretty reasonable and sporadic - especially lately. I don't have an inherent tolerance at this point; I'm curious if the Wellbutrin created a tolerance via prolonged DA/NE exposure.

about the mdma I believe so, I was worried about that the day I did that...

and yes I really think the DA/NE drugs could definitely have an effect like that... its not just possible, to me it sounds plausible...

If your tolerance is high (even with sporadic use it never really seems to go down all the way), like mine its just so hard to use it at all especially for recreational purposes, I know I don't have the biggest one but still I know I should not have to take what I am takin to achieve what I'm looking for... so your tolerance to the amps to begin with even without the medication antidepressants like wellbutrin, could be the biggest role in your question.
One year ago, the wellbutrin aside I would have asked the same exact question just to a different extent... its very possible, especially with a tolerance to begin with... the main factor.

 

[sekio]

The way it works depends on the exact structure and binding affinity of each drug, as well as dose.

Normally, since the binding coefficient (Ki) for most reuptake inhibitors is very high in comparison to amphetamine's Ki, amphetamine is displaced or blocked and cannot bind to the receptor and produce effects. The drug with the lowest Ki determines the effect, and displaces drugs of higher Ki.

Wellbutrin is a fairly strong NDRI so it will block both neurotransmitters release to some extent when co-administered with amphetamine. It's probably out-competing amphetamine given the large doses many people take (in comparison to amphetamine).

Disclaimer: i'm not a pharmacist.

 

[m060mm]

Thanks Sekio - your answer made me realize that it's not necessarily so complicated; I should have just looked up binding affinities and IC50's. I guess what threw me off is that this combo is a synergy for most, and net loss for some.