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Negative side-effects of Stimulant+NMDA Antagonist combinations

Lightning-Nl

Lightning-Nl

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We're always talking about how DXM, or Mementine decreases glutaminergic activity which allows dopamine neurons to upregulate themselves and thus - you block most tolerance that would have been built up to the dopaminergic effects of stimulant drugs. It's also been noted that NMDA antagonism can block most, if not all, neurotoxic effects of Amphetamine and other stimulants (specifically the study said Methylphenidate). These are all good things, except when they're not. Because like most drugs - 99% of all NMDA antagonists aren't purely selective for glutamate.

DXM is a potent Serotonin and Norepinephrine reuptake inhibitor, Sigma-1 agonist, and nAChR antagonist. All of this increases heart rate....extremely. Add that on top of a stimulant and you have yourself.....probably some potent cardiotoxic effects. Amphetamine (for instance) is also a substrate of CYP2D6. So is DXM. So by combining the two, you increase the risk of side-effects by slowing down both Amphetamine's and Dextromethorphan's metabolism.

I thinks this thread is appropriate because the negative side-effects of this combination haven't been studied (at all as far as I'm aware) and while there are some very promising, good effects from this combination of drugs - there may be toxic effects that we're unaware of. Who knows, maybe this really is a perfect combination. Maybe it's not. Either way, I believe it should be discussed.
 
There have been dozens of clinical trials concerning DXM, have any shown signs of tachycardia?
 
DXM is a potent Serotonin and Norepinephrine reuptake inhibitor, Sigma-1 agonist, and nAChR antagonist. All of this increases heart rate....extremely.
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There's lots of antidepressants that fit this profile and yet aren't cardiotoxic. Increasing heart rate doesn't equal death of cardiac tissue, or we wouldn't encourage excercise. It's only when it runs unopposed for a long time, or it's particularly severe that it's a concern. (c.f. nobody tells you to avoid coffee because it will damage your heart in the short term, the consensus is more like, don't drink 2+ cups a day for 10+ years)

Now, if we were talking about hERG affinity, that's a concern. Or strong sodium channel blockade. Or 5ht2b agonism. But in and of itself, DXM just ain't cardiotoxic. See also: It's approved for pseudobulbar affect and OTC cough suppression.

It's also good to note that at "typical" doses of sub-100mg, DXM acts mostly as a SNRI with sigma-1 agonism. Its affinity for most targets is rather low... dissociative effects from such doses are probably due to the far more potent metabolite DXO. Low doses as used for tolerance reduction seem to be relatively friendly.
 
sekio said:
There's lots of antidepressants that fit this profile and yet aren't cardiotoxic. Increasing heart rate doesn't equal death of cardiac tissue, or we wouldn't encourage excercise. It's only when it runs unopposed for a long time, or it's particularly severe that it's a concern. (c.f. nobody tells you to avoid coffee because it will damage your heart in the short term, the consensus is more like, don't drink 2+ cups a day for 10+ years)
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I'm talking about resting heart rate. I've personally measured mine when taking 20 milligrams of Amphetamine and then 30 milligrams of DXM. My no drug normal heart rate was 90 beats per minute. My amphetamine resting heart rate was about 110 beats per minute, but my amphetamine + DXM resting rate was 151 beats per minute. That's hypertensive. Plus my chest will feel incredibly tight. I'm not trying to base anything off of just my personal experience, however, it stands to reason that an SNRI + a Dopamine/Norepinephrine/Serotonin releasing agent is going to fuck with your heart.....a ton...

Then once DXM get's fully metabolized into DXO, then you have antiglutaminergic effects to be concerned about. Which will always upregulate the monoamines even further, thus raising your heart rate. Also, I'm not trying to claim that this is the only danger of NMDA antagonists + Stimulants either. There could be other possible dangers that haven't been thought of yet. And that's why I thought this deserved a thread.
 
http://journals.lww.com/cardiovascu...&article=00003&type=Abstract&desktopMode=true

DXM does have some hERG effects, so using heavy amounts of it while on methadone and citalopram with a family history of SCD might not be the best.

High heart rate is tachycardia, not hypertension. Have you taken your blood pressure as well? Notably, variation across sympathetic/parasympathetic responses with baroreceptors can really make a large difference.

For example, stimulant abuse in some people can lead to activation of that reflex, leading to very low blood pressures. Which then, because people think that they can "feel" blood pressure accurately all the time (Read: essential hypertensive cases), or immediately go to anti-hypertensives, can lead to syncope. Not a great time.

150 isn't a heart rate you want at resting though. I would stop that before you get into any heavy tachycardic runs or SVT. For me, I have orthostatic tension and the response above from tranylcypromine, an MAO inhibitor, and I get pretty high as well. Desipramine was fun as well. (For reference, my resting was usually 55-60 with caffeine, now about 95 with high variation.)

For a healthy person wanting to avoid tolerance though, that level of cardiac stress is not a reasonable tradeoff. That level isn't typical, though.

Probably would be a good idea to get a baseline EKG and monitor a few things with similar combinations, but I'd go with Sekio's view on this under normal use.

Normal use doesn't seem to be the case here, though.
 
With recreational dosages, stimulants and dissociatives can induce synergistic manic states sometimes, particularly if the dosage of one or both is pushed too high.

ebola
 
Whoever made that a separate thread - thank you. @thread What are other possible side-effects of this combination? (besides possible cardiovascular issues?)
 
Just DXM and amphetamine? There's lots of stimulants, and lots of NMDA antagonists with varying interaction profiles.

The only thing I can think of is that if you are prone to, ahem, euphoriant-style dosing regimens, adding what are traditionally considered 'crazy drugs' to your stimulant isn't going to do your psyche any good. Especially, say, MXE plus amphetamine... good way to end up institutionalized if you don't keep doses on lockdown.
 
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sekio said:
Just DXM and amphetamine? There's lots of stimulants, and lots of NMDA antagonists with varying interaction profiles.

The only thing I can think of is that if you are prone to, ahem, euphoriant-style dosing regimens, adding what are traditionally considered 'crazy drugs' to your stimulant isn't going to do your psyche any good. Especially, say, MXE plus amphetamine... good way to end up institutionalized if you don't keep doses on lockdown.
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I'm assuming that includes plugging of therapeutic dosages? Because I never go above 40 milligrams of AMPS a day, but the way I administer it varies. Also, it's interesting that you say that because since I've started plugging amphetamine - I've noticed a big increase in hallucinations. Especially when I take the DXM at the end of the day (the DXM dose is never over 60 milligrams), I have near, full-fledged, visual hallucinations. Only very slight, very minor auditory hallucinations - but the visual stuff is definitely getting worse.

I'm glad you brought that up because I've actually been worried about it TBH. As it is, right now, I'm having strong visual hallucinations every day. I've been able to ignore it successfully, and since I haven't noticed any other symptoms of psychosis going on (eg. paranoia, thought distortions, etc.) I've let it slide - which again, makes me glad that you brought this up because I really should address this.

Anyways, what's your take on what I just said?
 
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Uh... stop taking amphetamine, DXM and most other monoaminergics before you either have a psychotic break, cardiac arrest, or stroke. You need serious medication adjustment if you have regular hallucinations, it shouldn't be something you just brush off.
 
I was gonna argue with you. Try to justify everything, and say that it's okay. But you're right. Fortunately my hallucinations atm are just (mainly) shadow people, and illusions of faces (seeing human faces everywhere and in everything). The human faces thing I've actually had my whole life, however, this med regiment has made it a lot worse.

Anyways, I'll stop plugging, and stop the DXM and see how that alters my symptoms. Because, this only really stared when I started plugging amps.
 
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