I got there via a different rabbit hole where someone was trying to use memantine's liver enzyme inhibition to prevent the metabolism of bupropion into hydroxybupropion.
Memantine inhibiting any liver enzyme to a relevant degree, do you have any source for this? Most of it is excreted without metabolism afaik..
A few years ago, I used to love DXM. It was this exact combination that 'broke' my CEVs for all dissociatives.
The first report ever I read where somebody got the same phenomenon. Just for me it wasn't bupropion but paroxetine, I was young and stupid, took a regular DXM dose (maybe 300-450mg) on top of the newly started paroxetine.. the trip started as usual but too there was a very weird feeling, that something is going to go terribly wrong, and then the colorful CEVs just freezed. I got a constant image like an oriental carpet which wouldn't change the least bit anymore. Eyes closed, eyes opened and closed again - the very same image would continue and it began to scare the shit out of me, given the weird, hot syrup like overall feeling and nausea.. nothing else which I remember of, the stuff faded away after some long hours, but ...
I never ever got any colors again from any dissociative. From then on I got no, or just slight black/white CEVs and no OEVs. Shrooms stopped to work, yet recently 1cP-LSD had the same effects as in the others, and gave me beautiful visuals, so it's mostly about dissociatives but still wondering and scared off whatever it might have done. I suspect it caused a permanent high serotonin tolerance (fried some 5-ht producing neurons, maybe, but guess it's much more complicated than that) which renders me unable to function w/o some sort of antidepressant, inability to trip with things less potent than the lysergamides, etc ...
Dextromethorphan/Bupropion: A Novel Oral NMDA (N-methyl-d-aspartate) Receptor Antagonist with Multimodal Activity - PubMed (nih.gov)
An Ingredient in Cough Syrup Could Work as an Antidepressant (vice.com)
Efficacy of dextromethorphan for the treatment of depression: a systematic review of preclinical and clinical trials - PubMed (nih.gov)
That said, as
@Pfafffed already pointed out, it's now in Phase 3 trials, and from my experiences with taking just regular recommended dosages of DXM against cold whilst on bupropion 150mg/d, I can vouch for its effectiveness. In the trials they're also using low dosages like 25-40mg alongside 105mg bupropion etc. which makes sense, when it's a 1000% exposition we'd have 250mg DXM, which makes a good antidepressant dosage, just minus the dissociation from DXO and with a longer half life.
DXM is indeed an unique antidepressant, be it alone or with an enzyme inhibitor. My hunch is that the classification as SNRI is wrong, and it's a slight inverse agonist at the transporter (like methylphenidate and cocaine are, just that they're stronger) leading to some 5-ht release. It has a warmth all the other ADs lack, venlafaxine/more tramadol has a very slight aura of this (and a terrific withdrawal syndrome) but DXM is stronger. Or if not then it has to do with sigma, and/or possibly even a yet-to-be-identified target. Also it works almost instantly, in opposition to regular S/NRIs with their waiting period.
With bupropion added you get a stimulation bomb, for plain depression maybe the combination with low dose quinidine (a fraction of what's needed against arrythmia) might make sense too but they're obviously looking for a new cash cow.
Also it's not (primarily? DXM has some affinity too) about NMDA antagonism because while memantine too can have some sort of antidepressant effect, it's very different qualitatively.
Just don't rush into high dosages, seems like a serotonin-noradrenaline syndrome can and will kill something relevant for closed eye visuals ...
