Misc Could a Prescription Permanently Ruin My Tolerance? (DXM, bupropion)

[sillypillyoclock]

I’ve been prescribed the newly approved Auvelity, which is an extended release tablet of 45mg of dextromethorphan HBr and 105mg of bupropion HCl. I’m on my seventh day, and have a bit of an unusual reaction to it, it gets me quite high (vast majority of people do not get any recreational value out of this). That’s not really what this post is about, though (I asked that question in another place).
I’ve heard reports of people who take Auvelity suddenly have it stop working. Someone described it as a “Flowers for Algernon” type situation. Could this be because of DXM’s notorious tolerance building issue? Could this be avoided by altering the dosing schedule (i.e, 2 weeks on, 2 weeks off)?
Or am I doomed to slowly lose DXM’s magic, and its magical antidepressant qualities, and develop an irreversible tolerance? I should also mention I am a poor metabolizer of CYP2d6.
I’m honestly really worried about this. This medicine is really helping my depression so far, and I don’t want to ruin that. Even this measly XR 45mg feels a bit like low dose ketamine for me.
Of course, I wouldn’t change anything about my medications without consulting my provider.

 

[SpiralusSancti]

You’ll stop feeling obvious effects pretty soon but not antidepressant effects. Will you eventually loose antidepressant effects too, who knows but you’re lucky enough that you found something that works for you and that’s a chance to work on yourself and everything you can so eventually you don’t need that medicine anymore.

Definitely shouldn’t worry about things you ask but enjoy and get most out of it for however long it’ll work. You could prolong high feeling by alternating days of and on it but if you insist on a such a use than rather go for an “use as needed” approach.

 

[sillypillyoclock]

You’ll stop feeling obvious effects pretty soon but not antidepressant effects. Will you eventually loose antidepressant effects too, who knows but you’re lucky enough that you found something that works for you and that’s a chance to work on yourself and everything you can so eventually you don’t need that medicine anymore.

Definitely shouldn’t worry about things you ask but enjoy and get most out of it for however long it’ll work. You could prolong high feeling by alternating days of and on it but if you insist on a such a use then rather go for an “use as needed” approach.

Since I’m at such a fixed dose, would larger doses of DXM still have an affect on me? Obviously not going to try that while I’m on this med, but if it ever stops working, would I be able to do a larger dose (i.e 70-90mg) and still get effects from that? And DXM doesn’t have a cross tolerance with ket, does it?
I know I should stay in the moment, but I have this feeling I’ve discovered something life changing for myself, and I have to do whatever possible to ensure an ideal outcome. I don’t want to “Flowers for Algernon” myself :,( This is some of the most pronounced relief from depression I’ve had since I was perhaps 8 or 9. I’m terrified of slipping away again.

 

[SpiralusSancti]

Since I’m at such a fixed dose, would larger doses of DXM still have an affect on me? Obviously not going to try that while I’m on this med, but if it ever stops working, would I be able to do a larger dose (i.e 70-90mg) and still get effects from that? And DXM doesn’t have a cross tolerance with ket, does it?
I know I should stay in the moment, but I have this feeling I’ve discovered something life changing for myself, and I have to do whatever possible to ensure an ideal outcome. I don’t want to “Flowers for Algernon” myself :,( This is some of the most pronounced relief from depression I’ve had since I was perhaps 8 or 9. I’m terrified of slipping away again.

You are taking 2 AD’s in one pill and can’t be sure how much each alone would have effects. Upping the dose of DXM would surely have effects but higher and instant release doses would be doing significantly more damage than prescription you have, definitely if used often.

I don’t know history of your drug use and abuse but by what you describe I think that you either have a great response to medicine you got prescribed or are one of those who respond great to dissos. If it’s second maybe you would benefit more with using a lot higher dose every few weeks instead dosing it daily? As, at least that’s mine and a lot of peoples theory that at least some part of positive effects of both dissos and psychedelics comes from the experience/high itself as otherwise we would have effective non-psychoactive alternatives since long ago. But it seems that neither non/less psychoactive NMDA antagonists nor 5htx agonists don’t really work, or don’t work nearly as good.

All dissos have cross tolerance, as do all other group of drugs within same group, but to what extent depends of similarity between substances, chemical and/or pharmachological. DXM and K don’t have nearly as pronounced cross tolerance as K and other arylcyclohexilamines. At least if we talk about cross-tolerance when it comes to immediate effects but as for beneficial, medicinal effects, I don’t think that’s investigated nearly enough to give solid conclusions. If you ask will you have K as an alternative if/when DXM stops working, sure, at least to some extent, but you should rather make sure DXM keeps working.

 

[sillypillyoclock]

You are taking 2 AD’s in one pill and can’t be sure how much each alone would have effects. Upping the dose of DXM would surely have effects but higher and instant release doses would be doing significantly more damage than prescription you have, definitely if used often.

I don’t know history of your drug use and abuse but by what you describe I think that you either have a great response to medicine you got prescribed or are one of those who respond great to dissos. If it’s second maybe you would benefit more with using a lot higher dose every few weeks instead dosing it daily? As, at least that’s mine and a lot of peoples theory that at least some part of positive effects of both dissos and psychedelics comes from the experience/high itself as otherwise we would have effective non-psychoactive alternatives since long ago. But it seems that neither non/less psychoactive NMDA antagonists nor 5htx agonists don’t really work, or don’t work nearly as good.

All dissos have cross tolerance, as do all other group of drugs within same group, but to what extent depends of similarity between substances, chemical and/or pharmachological. DXM and K don’t have nearly as pronounced cross tolerance as K and other arylcyclohexilamines. At least if we talk about cross-tolerance when it comes to immediate effects but as for beneficial, medicinal effects, I don’t think that’s investigated nearly enough to give solid conclusions. If you ask will you have K as an alternative if/when DXM stops working, sure, at least to some extent, but you should rather make sure DXM keeps working.

Yeah I definitely have a unique reaction to this combination, as I haven’t seen many people report any recreational value from it, and none getting as high as I have. However, even many of the people who don’t get high from this medicine still get substantial relief from depression (as demonstrated from both online anecdotes and the trials involved in Auvelity’s FDA approval). It’s also a more substantial increase in relief than bupropion alone.
What’s curious to me is, from what I understand from reading the famous DXM FAQ on Erowid, being a poor metabolizer of 2D6 should cause less of a high, not more. Am I wrong about this, or is there another genetic factor at play here?
I guess it’s only speculation to ask what the implications are of DXM use and tolerance are on someone who’s a poor metabolizer of 2D6. Doesn’t seem to be a subject in which there is much literature.
As for me, I’ve definitely have had periods of heavy use on various substances (nothing too hard), but have always been able to know when it’s time to quit. Probably at least partly due to my OCD; the idea of causing irreparable damage to myself is terrifying enough to CT any substance at the first sign of trouble. These days, however, I’m more stable and stick to occasional legal highs and only using my prescriptions as directed.
I’ll definitely ask my provider about some of these questions regarding dosing schedules. She’s generally pretty receptive and open. My particular brand of depression occurs primarily for only 2/4 weeks of the month. So maybe that would be enough for me. I guess it’s down to experimenting now.
I do find all of this fascinating though! I’m honestly finding this really mentally enriching to try and unravel. Makes me want to go to college and learn biochemistry and pharmacology. Ah, I do miss school. You seem pretty knowledgeable about this stuff, I admire that

 

[Snafu in the Void]

or is there another genetic factor at play here?

There is definitely some sort of genetic factor in DXM that, under my assumption, is not related to 2d6 metabolization. It may possibly be neurological.

Some people like myself find DXM to be very dysphoric and does not produce pleasurable effects at any dose. Personally I hate the drug. 70mg, 100mg, 300mg, 600mg, it doesn't matter, it always makes me feel like shit and other than vague similarities in dissociative properties is completely unlike other disso drugs. DXM makes me feel depressed for many hours even after the drug wears off.

On the other hand, many people experience the opposite and get an extremely euphoric effect from it, to the point where they heavily abuse it in very high doses (1000mg+) and actually become physically addicted.

I don't think this discrepancy can be explained by being a poor or efficient metabolizer, usually that would just lend to either feeling the drug or not feeling the drug at all, such as in the case of poor opioid metabolizers.

Anyways, I find your reaction to this drug very peculiar, because in my own experience DXM does not have perceptible psychoactive effects at doses below 60mg (instant release). There must be some sort of potentiation or interaction going on between DXM and buproprion. The high you may be getting might possibly be more from the buprioprion, which is abuseable in itself.

Although do take care in trying to chase this high. Taking DXM in high doses in combination with antidepressants is inherently dangerous and can lead to permanent brain damage in extreme cases.

 

[sillypillyoclock]

There is definitely some sort of genetic factor in DXM that, under my assumption, is not related to 2d6 metabolization. It may possibly be neurological.

Some people like myself find DXM to be very dysphoric and does not produce pleasurable effects at any dose. Personally I hate the drug. 70mg, 100mg, 300mg, 600mg, it doesn't matter, it always makes me feel like shit and other than vague similarities in dissociative properties is completely unlike other disso drugs. DXM makes me feel depressed for many hours even after the drug wears off.

On the other hand, many people experience the opposite and get an extremely euphoric effect from it, to the point where they heavily abuse it in very high doses (1000mg+) and actually become physically addicted.

I don't think this discrepancy can be explained by being a poor or efficient metabolizer, usually that would just lend to either feeling the drug or not feeling the drug at all, such as in the case of poor opioid metabolizers.

Anyways, I find your reaction to this drug very peculiar, because in my own experience DXM does not have perceptible psychoactive effects at doses below 60mg (instant release). There must be some sort of potentiation or interaction going on between DXM and buproprion. The high you may be getting might possibly be more from the buprioprion, which is abuseable in itself.

Although do take care in trying to chase this high. Taking DXM in high doses in combination with antidepressants is inherently dangerous and can lead to permanent brain damage in extreme cases.

I find my reaction very intriguing as well. I’ve taken bupropion before, many years ago, and had no recreational experience from it whatsoever. It didn’t even treat my depression very well, honestly.
I’ve also had DXM before. A few years ago, I got sick and decided to try a little bit, because why not. Even at therapeutic doses, I noticed slight psychoactive effects. I didn’t know much about the substance at the time, so I didn’t find it unusual.
I ended up wanting to try a larger dose, and after doing some light research, got absolutely blasted off polystirex. I can’t remember the dose I took, but I’m a bit of a hypochondriac so I doubt it was anything crazy. I was high for like 40 hours. It honestly wasn’t pleasant. Not necessarily an awful experience, either. I just kind of wanted it to be over.
Once the high was over, I expected a nasty comedown. But it never happened. In fact, I felt… good? Great, even? This was prior to Auvelity being approved, so there wasn’t a ton of evidence I could find online about the antidepressant qualities of DXM. Cut to me finding out about this combination being approved by the FDA, getting a sample from my provider, and here I am.
I definitely don’t plan on adding any additional DXM to my regimen while I’m taking Auvelity. Auvelity is made with a time release, so adding more DXM would be far too unpredictable. I’m also on a couple other medications.
I am very worried about losing the antidepressant effects I’m getting, less about the ability to get high. What if I take it as prescribed, and then one day it doesn’t work anymore? Do I need to be proactive and experiment with a less frequent dosing schedule? Sigh… I think I worry too much, lol.

 

[SpiralusSancti]

You do worry too much and probably without good reason.. As you say you have depression just about half of the time and both bupropion and DXM have pretty much immediate effects unlike SSRIs and most other ADs taking it as needed might be good idea. But do talk about it with doctor. Only negative side of such use I can think of is that you won’t get used to side-effects of bupropion, or better said they won’t go away but since you like this medicine so much I doubt you get any anyway.

As you had such a long effects, even if it was high dose that’s far longer than it lasts for most people maybe reason it works so well for you is in fact, among other things you metabolise poorly as, especially in combo with bupropion it causes something unusual.

Have you ever tried other NMDA antagonist?

Also I’m sure you know DXM is dangerous, much more so than ketamine in many combos so if/when you decide to give it another try you should do it alone and not in potentially dangerous combo.

May I ask what are other meds you take? As on top of bupropion and DXM they might have strong synergy.

 

[WellTram]

Bupropion will block CYP2D6 for a long time after you stop taking it. For example, codeine And tramadol both work great for me but not when i was on bupropion and even month after i quit bupropion it wasn't back to normal and i guess the same Will happen with dxm.