Calculating equivalent dosages of different drugs. Ketamine vs DXM

[Renald]

I want to approximate the NMDA activity of ketamine to the DXM, what dosage of ketamine would be equivalent to DXM as NMDA antagonist. The problem arises with Ki values , they are very different. Also, there are plenty of NMDA receptors such as Glutamate-NMDA, NMDA-PCP site, Glutamate-NMDA-MK801 etc, which one is responsible for dissociative effects of both drugs? Can I compare two substances based on their Ki values and using bioavailability, protein binding, volume of distribution parameters to compare the dosages of different substances? Help would be appreciated!

 

[sekio]

I don't think there is an easy way to measure the equaivalency of the two drugs mathematically.

Also, there are plenty of NMDA receptors such as Glutamate-NMDA, NMDA-PCP site, Glutamate-NMDA-MK801 etc,

Are you sure about this? To my knowledge NMDA receptors can have slightly differing NR1 and NR2 subunits, but they are all glutamate receptors that bind NMDA. The PCP site is the uncompetitive binding site that other dissociatives bind and block - it's the same as the MK801 binding site, it's also where DXM acts, and memantine.

The two other regulatory sites on the NMDA receptor are the glycine binding site and the polyamine site. I don't think that recreational dissociatives bind there, though.

Can I compare two substances based on their Ki values and using bioavailability, protein binding, volume of distribution parameters to compare the dosages of different substances?

Sort of, but you'll have better luck just looking at the effects of different doses and figuring out at what dosage it takes the two drugs to produce similar effects.

The problem I can see that you'll have is, DXM is not exactly a selective dissociative... it's actually a much stronger norepinephrine & serotonin reuptake inhibitor than a dissociative. Its metabolite compounds dextrorphan (DXO - O-demethylated product) and 3-methoxymorphinan (nor-DXM, N-demethylation product) are significant contributors to the dissociative effects as well. So you should consider the metabolism of DXM in the body which can be nonlinear (e.g. taking bigger doses at once versus smaller doses spaced apart can actually result in less beign converteed to DXO). You end up having to do math to figure out how 2 or 3 different drugs combine to make their effects.

It's simpler to just read Erowid experience vaults... in my personal opinion I would suggest that about 800-900mg of DXM, a third plateau dose, is close to a 200mg intranasal dosage of ketamine. They both get you to the edge of anesthesia. However the time course is different (DXM takes longer to onset and lasts much longer), the body load is different, the high is much qualitatively different too. You can't snort or inject DXM, and eating ketamine is a waste, so that also makes doses hard to compare.

 

[dopamimetic]

Thanks, sekio I've struggled to verbalize all this - and as always there are some new bits here and there I've yet to learn.

the glycine binding site (...) I don't think that recreational dissociatives bind there, though.

According to wikipedia, DXO antagonizes the glycine site as well, but no source for that there.

Don't know if it's relevant at all, but DXM (weakly) agonizes all three opioid receptors. As the Ki values are detailed only for DXM and not DXO, it would be interesting if the latter binds to opioid receptors too. As for an anecdotal report, in my early DXM days I felt a very unique comfortable, numbing warmth together with histamine reaction (itching etc) when effects began to rise. This lasted for maybe 1-3 hours and subsided then into 'cold' dissociation.

But, of course, dissociatives and 'opioid-alike' feelings are debatable. Like with MXE, even though I'd say that DXM was more opioid-ish. More than some of the true opioids I've tried (many years and time to build tolerance) later.

 

[endotropic]

Also, there are plenty of NMDA receptors such as Glutamate-NMDA, NMDA-PCP site, Glutamate-NMDA-MK801 etc, which one is responsible for dissociative effects of both drugs?

Those are different sites on the same receptor. NMDA receptor antagonists can bind to and inhibit the receptor at at least 4 sites, look at the images on this page: https://en.wikipedia.org/wiki/NMDA_receptor_antagonist

 

[serotonin2A]

For the purposes of the drugs that people on BL find interesting (PCP, ketamine, methoxetamine, etc), the relevant site is the PCP/MK-801 site located within the channel. Orthosteric antagonists can produce hallucinogenic effects but they are not used recreationally. Similarly, I'm not aware of any recreational drugs that act through non-competitive allosteric sites (such as the polyamine site) or the glycine co-agonist site.

 

[Renald]

Wikipedia classify ketamine as non-competitive antagonist vs DXM, MXE, PCP, nitrous and memantine as uncompetitive ones.
What is orthosteric antagonist?

 

[serotonin2A]

Wikipedia classify ketamine as non-competitive antagonist vs DXM, MXE, PCP, nitrous and memantine as uncompetitive ones.
What is orthosteric antagonist?

Wikipedia is filled with errors. Most people don't understand the difference between "uncompetitive" and "non-competitive", and that includes the people that edited the article on wikipedia. Ketamine, MXE, PCP, and memantine all bind to the same site.

Orthosteric ligands bind to the same site as the endogenous agonists; agonists can either act through the orthosteric site or through an allosteric site.

 

[X11400]

Wikipedia is filled with errors. Most people don't understand the difference between "uncompetitive" and "non-competitive", and that includes the people that edited the article on wikipedia. Ketamine, MXE, PCP, and memantine all bind to the same site.

Orthosteric ligands bind to the same site as the endogenous agonists; agonists can either act through the orthosteric site or through an allosteric site.

But what about dxm? It's commonly described as being dirty by the people who hate on it.

 

[Cotcha Yankinov]

But what about dxm? It's commonly described as being dirty by the people who hate on it.

DXM probably feels "dirty" because its far from a selective NMDA antagonist - it has numerous actions that can muddy the experience. When you compare the headspace of DXM vs. something like memantine you may recognize what is NMDA antagonism and what extra part of DXM's effects may be moreso due to reuptake inhibition/sigma 1 receptor agonism et cetera.

At least to me, subjectively memantine feels much cleaner.

That isn't to say that DXM and memantine would be the same if all they did was block NMDA receptors (because they block the NMDA receptors a bit differently even though they bind to the same site inside the NMDA channel), but my point is that DXM is far from selective for NMDA receptors

 

[X11400]

DXM probably feels "dirty" because its far from a selective NMDA antagonist - it has numerous actions that can muddy the experience. When you compare the headspace of DXM vs. something like memantine you may recognize what is NMDA antagonism and what extra part of DXM's effects may be moreso due to reuptake inhibition/sigma 1 receptor agonism et cetera.

At least to me, subjectively memantine feels much cleaner.

That isn't to say that DXM and memantine would be the same if all they did was block NMDA receptors (because they block the NMDA receptors a bit differently even though they bind to the same site inside the NMDA channel), but my point is that DXM is far from selective for NMDA receptors

Don't get me wrong DXM can feel shitty with regards to the gastrointestinal tract, and enzyme deficiencies should not be taken lightly. These attributes can suck at times but are we really gonna hate on psilocybin mushrooms/mescaline also? And back to the statement from before with regards to NMDA receptor antagonism, what about Phencyclidine, or Ketamine? None of these drugs are pure NMDA antagonists either. All this line of reasoning is is a gross oversimplification of the pharmacology of said substances. Just like the "phenethylamine vs tryptamine" threads which always end in pure conjecture or placebo being the line of reasoning, or the Psychedellics vs dissociatives which usually end in a naturalistic fallacy. My point here is that, there seems to be an unreasonable amount of hate towards Dextromethorphan specifically as a dissociative which starts to lead to a group mentality grounded not in empirical evidence, but negative stigma, condescension, and speculation. I even see people go as far as saying that Ketamine is even inherently safer than DXM where the former has shown significant urinary tract complications which the latter has not. Also to add (I almost forgot) Memantine has not only Glutaminergic activity but chollinergic (nicotinic), dopaminergic,sigmaergic, as well as antagonistic serotoniergic effects (as far as I can tell) so that pretty much contradicts your statement regarding this supposed pure NMDA receptor antagonism. This further proves my point about people irrationally hating on DXM. Another thing is that NMDA antagonism by itself without the other stimulatory effects is actually quite boring and an experience that usually isn't worth trying. That is of course my own subjective intuition and it should be taken as such.

 

[Cotcha Yankinov]

And back to the statement from before with regards to NMDA receptor antagonism, what about Phencyclidine, or Ketamine? None of these drugs are pure NMDA antagonists either. All this line of reasoning is is a gross oversimplification of the pharmacology of said substances.

Ketamine is indeed an SNRI but I don't think its quite as much of an SNRI as DXM and not as promiscuous at other sites like Sigma 1 receptor. This is in comparison to DXM which works to suppress cough at very low doses via effects on Sigma1. I'm not 100% sure exactly what targets contribute to DXM's subjective "dirtyness" but I don't think that those anecdotal reports are invalid.

There are certainly differences between the NMDA antagonists that have a lot to do with their binding proclivities. PCP can be a tad more psychotomimetic and its possible that this is due to its direct effects on dopamine which other NMDA antagonists may not share.

there seems to be an unreasonable amount of hate towards Dextromethorphan specifically as a dissociative which starts to lead to a group mentality grounded not in empirical evidence, but negative stigma, condescension, and speculation. I even see people go as far as saying that Ketamine is even inherently safer than DXM where the former has shown significant urinary tract complications which the latter has not.

Ketamine can be used as an anesthetic in emergency situations specifically because it is safe in terms of physical safety (neurogenic bladder risk should be extremely minimal in a one-off use).

But you won't see ER physicians giving people DXM for anesthesia for a few reasons. For starters the intense NRI can low the seizure threshold. There are the liver enzyme/metabolism issues. It can induce intense itching/histamine release in some people. It could be hard on the liver itself, especially for people stabilized on other medications that need to be kept in a narrow concentration range (anti-epileptics). It could be more likely to produce adverse psychiatric effects in the short term, although lord knows all NMDA antagonists can cause psychiatric side effects in the long term. Oftentimes elderly patients have a hard time recovering from anesthesia with normal anesthetics.

Also to add (I almost forgot) Memantine has not only Glutaminergic activity but chollinergic (nicotinic), dopaminergic,sigmaergic, as well as antagonistic serotoniergic effects (as far as I can tell) so that pretty much contradicts your statement regarding this supposed pure NMDA receptor antagonism. This further proves my point about people irrationally hating on DXM. Another thing is that NMDA antagonism by itself without the other stimulatory effects is actually quite boring and an experience that usually isn't worth trying. That is of course my own subjective intuition and it should be taken as such.

Memantine has glutamatergic activity? You're referring to effects on glutamate receptors other than NMDA? Blocking NMDA receptors leads to downstream glutamate release yes, but I don't believe its similar to ketamine with regards to hydroxynorketamine and the effects on AMPA receptors. I'm personally not aware of other glutamatergic effects.

I'm not saying the effects on nicotinic acetylcholine receptors don't help shape the subjective effects, nor the effects on 5-HT3 receptors, but that and NMDA antagonism may be all that memantine appreciably has going for it and thats certainly a whole lot less than DXM has.

Its very likely that memantine isn't an appreciable agonist at D2 receptors. There is a researcher Philip Seeman who loves to report D2 agonism with every drug on the planet, even when its probably not there. There are many incidences where Seeman reports D2 agonism/partial agonism and another lab can't confirm the results. I'm pretty sure the PDSP's screening showed memantine's D2 affinity was >10,000 Ki.

Activity at Sigma1R plays some role in memantine's (most ligands really) effects but its probably not as appreciable as DXM's sigma agonism. Even if the affinity/occupancy of Sigma1R is the same between DXM and memantine, we still have the issue of intrinsic efficacy. Sigma1R agonism might also be a bit context dependent in the sense that Sigma1R agonism related effects express themselves differently depending on the basal activity of the brain.

I see now what wiki wrote regarding Memantine/Sigma1R - "It acts as an agonist at the σ1 receptor with a low K_i of 2.6 µm (2600 nm).^[23] The consequences of this activity are unclear (as the role of sigma receptors in general is not yet that well understood) and memantine is probably too weak at the sigma binding site to exhibit significant agonist effects, only exhibiting partial agonism or antagonism. Some of memantine's adverse effects arise through this route."


My hunch is that the potent reuptake inhibition effects, effects at Sigma1R and histamine related effects can explain in part the "dirtyness" of DXM. When compared to something like memantine, I personally think that memantine feels subjectively much "cleaner" - In my experience you can tell what is the NMDA antagonism and what is missing compared to DXM - the almost psychotomimetic/"brain fry" portion of DXM.

"NMDA antagonism by itself without the other stimulatory effects is actually quite boring and an experience that usually isn't worth trying. That is of course my own subjective intuition and it should be taken as such."

It is indeed generally the case that NMDA antagonists with reuptake inhibition are more abuseable.

 

[X11400]

Ketamine is indeed an SNRI but I don't think its quite as much of an SNRI as DXM and not as promiscuous at other sites like Sigma 1 receptor. This is in comparison to DXM which works to suppress cough at very low doses via effects on Sigma1. I'm not 100% sure exactly what targets contribute to DXM's subjective "dirtyness" but I don't think that those anecdotal reports are invalid.

There are certainly differences between the NMDA antagonists that have a lot to do with their binding proclivities. PCP can be a tad more psychotomimetic and its possible that this is due to its direct effects on dopamine which other NMDA antagonists may not share.


Ketamine can be used as an anesthetic in emergency situations specifically because it is safe in terms of physical safety (neurogenic bladder risk should be extremely minimal in a one-off use).

But you won't see ER physicians giving people DXM for anesthesia for a few reasons. For starters the intense NRI can low the seizure threshold. There are the liver enzyme/metabolism issues. It can induce intense itching/histamine release in some people. It could be hard on the liver itself, especially for people stabilized on other medications that need to be kept in a narrow concentration range (anti-epileptics). It could be more likely to produce adverse psychiatric effects in the short term, although lord knows all NMDA antagonists can cause psychiatric side effects in the long term. Oftentimes elderly patients have a hard time recovering from anesthesia with normal anesthetics.



Memantine has glutamatergic activity? You're referring to effects on glutamate receptors other than NMDA? Blocking NMDA receptors leads to downstream glutamate release yes, but I don't believe its similar to ketamine with regards to hydroxynorketamine and the effects on AMPA receptors. I'm personally not aware of other glutamatergic effects.

I'm not saying the effects on nicotinic acetylcholine receptors don't help shape the subjective effects, nor the effects on 5-HT3 receptors, but that and NMDA antagonism may be all that memantine appreciably has going for it and thats certainly a whole lot less than DXM has.

Its very likely that memantine isn't an appreciable agonist at D2 receptors. There is a researcher Philip Seeman who loves to report D2 agonism with every drug on the planet, even when its probably not there. There are many incidences where Seeman reports D2 agonism/partial agonism and another lab can't confirm the results. I'm pretty sure the PDSP's screening showed memantine's D2 affinity was >10,000 Ki.

Activity at Sigma1R plays some role in memantine's (most ligands really) effects but its probably not as appreciable as DXM's sigma agonism. Even if the affinity/occupancy of Sigma1R is the same between DXM and memantine, we still have the issue of intrinsic efficacy. Sigma1R agonism might also be a bit context dependent in the sense that Sigma1R agonism related effects express themselves differently depending on the basal activity of the brain.

I see now what wiki wrote regarding Memantine/Sigma1R - "It acts as an agonist at the σ1 receptor with a low K_i of 2.6 µm (2600 nm).^[23] The consequences of this activity are unclear (as the role of sigma receptors in general is not yet that well understood) and memantine is probably too weak at the sigma binding site to exhibit significant agonist effects, only exhibiting partial agonism or antagonism. Some of memantine's adverse effects arise through this route."


My hunch is that the potent reuptake inhibition effects, effects at Sigma1R and histamine related effects can explain in part the "dirtyness" of DXM. When compared to something like memantine, I personally think that memantine feels subjectively much "cleaner" - In my experience you can tell what is the NMDA antagonism and what is missing compared to DXM - the almost psychotomimetic/"brain fry" portion of DXM.

"NMDA antagonism by itself without the other stimulatory effects is actually quite boring and an experience that usually isn't worth trying. That is of course my own subjective intuition and it should be taken as such."

It is indeed generally the case that NMDA antagonists with reuptake inhibition are more abuseable.

Hey, if I seem to be a dick undermining everything that you said then I'm sorry, but back to these supposed "anecdotal reports." Do you think it's impossible for societal beliefs about certain drugs can effect the perceived subjective effects of a drug? This is kind of thinking parallels with the threads where many say that Tryptamines are inherently more spiritual than amphetamine psychedelics. Also, Seizures from dxm are not only extremely rare for nonepileptic individuals, they also usually occur on the high end of overdoses. This also applies to Ketamine, which is a Dri like pcp and lsd. Ketamine and pcp also have sigmaergic activity just like dxm. In clinical trials, dxm also has positive antidepressant properties and a certain kind of neuroprotective affinity. Another thing is, when you try to blame a drug specifically for a small percentage of people having allergic reactions, your argument starts to loose credibility because anything that has matter can cause an allergic reaction in a theoretical sense. Also, how exactly can a drug even feel "dirty"? That doesn't make sense, once again that ties into biased applications of the anthropomorphizing of a chemical. Nobody's trying to deny that a drug can't have side effects because that's nothing more than a pipe dream, but if you're going to keep bashing a chemical based off limited experience, ignorance, and/or misuse (which I don't think you're trying to do but this is a genralized statement for those that hate the chemical)
then I'm afraid that you should do the same for every other substance. Oh and one last thing, try not to be so hung up on Extremes of Ki, when it's obvious that all of the different receptors contribute to the subjective experience in one way or another.

 

[Cotcha Yankinov]

Hey, if I seem to be a dick undermining everything that you said then I'm sorry, but back to these supposed "anecdotal reports." Do you think it's impossible for societal beliefs about certain drugs can effect the perceived subjective effects of a drug? This is kind of thinking parallels with the threads where many say that Tryptamines are inherently more spiritual than amphetamine psychedelics.

Beliefs and conceptions about a drug can certainly affect the experience but the reports of DXM feeling subjectively dirty are rather ubiquitous and I don't think we should dismiss them lightly. There are enough pharmacological differences between DXM and "cleaner" feeling dissos that the anecdotal reports are validated empirically. See all the differences I pointed out between DXM and memantine.

Different psychedelics can produce different experiences and different dissos can produce different experiences. This may not even have to do with off-target effects - if we decided to tunnel vision on 5-HT2A and NMDA receptors for psychedelics and dissos, respectively, even differences in binding at the 5-HT2A receptor and NMDAr can result in differences between drugs. Different psychedelics activate 5-HT2A differently and different dissos block NMDA channels differently (even if they bind to the same site inside the NMDA channel).

Chalking up differences in subjective experiences to societal beliefs is unnecessary when there are such differences in the molecular actions of drugs - the latter is a much more tenable explanation for perceived differences.

Also, Seizures from dxm are not only extremely rare for nonepileptic individuals, they also usually occur on the high end of overdoses.

I was referring to the lowered seizure threshold as a reason as to why you won't see DXM prescribed in emergency situations as an anesthetic. I think the propensity for seizures under DXM is worse than ketamine, albeit they both aren't too appreciable under normal conditions (emergency conditions aside).

This also applies to Ketamine, which is a Dri like pcp and lsd.

What makes you think LSD is an appreciable DRI? Appreciable dopamine agonist sure, but DRI?

One problem you seem to keep running into is figuring out whether or not a listed effect of a drug is appreciable.

Ketamine and pcp also have sigmaergic activity just like dxm. In clinical trials, dxm also has positive antidepressant properties and a certain kind of neuroprotective affinity. Another thing is, when you try to blame a drug specifically for a small percentage of people having allergic reactions, your argument starts to loose credibility because anything that has matter can cause an allergic reaction in a theoretical sense.

I'm aware that they are active at Sigma1R, most ligands are. However, DXM is pretty active at Sigma1R at doses that don't produce behavioral effects. We still don't know about the functional activity at Sigma1R as well.

I'm aware DXM has antidepressant potential. I think all NMDA antagonists do. We're just trying to look at the pharmacological profile of DXM here and see what explains the reports of "dirtyness". If there are enough differences, like DXM/DXO are potent NRIs and induce histamine release, then the reports are validated to some degree.

What do you mean "when you try to blame a drug specifically for a small percentage of people having allergic reactions, your argument starts to loose credibility because anything that has matter can cause an allergic reaction in a theoretical sense"?

I'm saying that the histamine related effects associated with DXM (and opiates/opioids) can play a role in their perceived effects and the way it shapes a trip. One's head itching like crazy during a trip certainly has an effect on the experience and some people do get that... I believe the Sigma1 receptors were even (incorrectly) classified as opioid receptors at one point

Also, how exactly can a drug even feel "dirty"? That doesn't make sense, once again that ties into biased applications of the anthropomorphizing of a chemical. Nobody's trying to deny that a drug can't have side effects because that's nothing more than a pipe dream, but if you're going to keep bashing a chemical based off limited experience, ignorance, and/or misuse (which I don't think you're trying to do but this is a genralized statement for those that hate the chemical) then I'm afraid that you should do the same for every other substance.

Its a loose term. It could mean that some people get more scatter brained thoughts, more brainfog, more internal word salad et cetera. It could also be a physical sensation, RE: itching/histamine

Oh and one last thing, try not to be so hung up on Extremes of Ki, when it's obvious that all of the different receptors contribute to the subjective experience in one way or another.

Except there are cases where affinity at a target is so low that it doesn't appreciably contribute to the effects of a drug.


I don't hate DXM. I just don't think its the optimal drug therapeutically or recreationally for most people, even if some people love it. All I'm trying to do however is explain the anecdotal reports rather than just dismiss them and act like those people have no idea what they're talking about. There are some very experienced psychonauts out there and I wouldn't be so quick to assume that all reports of DXM feeling dirty are from someone who just bought a bottle of cough syrup, chugged it, and wrote a trip report without having tried any other dissos for comparison.

 

[X11400]

Beliefs and conceptions about a drug can certainly affect the experience but the reports of DXM feeling subjectively dirty are rather ubiquitous and I don't think we should dismiss them lightly. There are enough pharmacological differences between DXM and "cleaner" feeling dissos that the anecdotal reports are validated empirically. See all the differences I pointed out between DXM and memantine.

Different psychedelics can produce different experiences and different dissos can produce different experiences. This may not even have to do with off-target effects - if we decided to tunnel vision on 5-HT2A and NMDA receptors for psychedelics and dissos, respectively, even differences in binding at the 5-HT2A receptor and NMDAr can result in differences between drugs. Different psychedelics activate 5-HT2A differently and different dissos block NMDA channels differently (even if they bind to the same site inside the NMDA channel).


Chalking up differences in subjective experiences to societal beliefs is unnecessary when there are such differences in the molecular actions of drugs - the latter is a much more tenable explanation for perceived differences.

So if its such an ambiguous term, then why are you even using it in a Scientific context to begin with? Don't you think using unsophisticated terminologies tend to enact emotional responses more readily than using more accurate terms? This line of reasoning clearly (once again) Has an effect on the perceived subjective effects of a drug (If you go into something expecting for the worse then it may happen) Once again, that is not to say that the possible physical side effects should be taken lightly so I do not know whats up with the misconstruction of my words. People have these same arguments about "classical Psychedelics" vs "Rcs". Also, with regards to the physical side effects, you never responded to my point pertaining to Psilocybin mushrooms and their gastrointestinal disturbances not preventing people from revering the mushrooms.

What makes you think LSD is an appreciable DRI? Appreciable dopamine agonist sure, but DRI?

One problem you seem to keep running into is figuring out whether or not a listed effect of a drug is appreciable.

Oops, I misspoke right there, my rushing on mobile version caused me to overlook some errors. Still yet, you keep assuming that modern neuroscience is sophisticated to even be able to properly describe the nuances of certain drugs in the first place (specifically as a response to what I said).

I was referring to the lowered seizure threshold as a reason as to why you won't see DXM prescribed in emergency situations as an anesthetic. I think the propensity for seizures under DXM is worse than ketamine, albeit they both aren't too appreciable under normal conditions (emergency conditions aside).

What degree and frequency of these seizures are you talking about? I always thought that Using any Excitatory drugs (Cannabinoid agonists, Serotonergic Psychedellics, Amphetamines, Anti Muscarinics, Dissociatives etc) Lowered the seizure threshold anyways. Also you're wrong on the reason why Ketamine is used in Anesthesia more than Dextromethorphan. The reason why Ketamine is used more as an anesthetic is because of the fact that Ketamine suppresses breathing less than other dissociatives which otherwise could be a problem considering the Sedative cocktails commonly used in General anesthetic preparations.

I don't hate DXM. I just don't think its the optimal drug therapeutically or recreationally for most people, even if some people love it. All I'm trying to do however is explain the anecdotal reports rather than just dismiss them and act like those people have no idea what they're talking about. There are some very experienced psychonauts out there and I wouldn't be so quick to assume that all reports of DXM feeling dirty are from someone who just bought a bottle of cough syrup, chugged it, and wrote a trip report without having tried any other dissos for comparison.

Lol, when did I ever say that all reports of DXM's negative effects were related to what you or I mentioned? Another strawman. The simple point that you still seem to be missing is that the MAJORITY of these reports correlate to bad planning, enzymatic deficiencies, and 3rd person influence (Propaganda, elitism, condescension of the majority of the users of dxm). Very little of these reports use actual data to come to the correct conclusion of why Dextromethorphan can be a "problem."

 

[Coolwhip]

X11400, I am going to go out on a limb here and say you've never taken ketamine.

 

[Cotcha Yankinov]

So if its such an ambiguous term, then why are you even using it in a Scientific context to begin with?

You originally introduced the term "dirty" into this discussion: "But what about dxm? It's commonly described as being dirty by the people who hate on it."

I have to say that the term "dirty" aptly describes how some people feel about it (including myself) relative to e.g. memantine and I can't think of a better cover-all term that those who have experienced the muddiness may connect with, thus I merely repeated the term dirty... There aren't really good objective measurements here so we have to rely on what we've got; subjective reports. Consciousness is something that is fundamentally subjective.. So how we would describe an experience fundamentally necessitates subjective terminology..

If you don't like the subjective reports, then what would you suggest we do to study the matter scientifically (seeing as you don't seem to be interested in the details of the pharmacology)?

Maybe objective measurements like:

"How often does the human head-twitch?"
"How quickly does the human scurry around their room?"
"How long does it take the human to find the submerged platform?"

People have these same arguments about "classical Psychedelics" vs "Rcs". Also, with regards to the physical side effects, you never responded to my point pertaining to Psilocybin mushrooms and their gastrointestinal disturbances not preventing people from revering the mushrooms.

The various side effects of DXM don't stop some people from revering the dextroverse as well. That doesn't mean that some people won't dislike either drug for whatever reason.

We can't just say "XYZ side effect that you get from that drug is all in your head - its just because of a preconceived notion about the drug, and the reason you don't feel that side effect from another drug in the same class is because you have different preconceived notions about that drug, not because of a difference in pharmacology."

Oops, I misspoke right there, my rushing on mobile version caused me to overlook some errors. Still yet, you keep assuming that modern neuroscience is sophisticated to even be able to properly describe the nuances of certain drugs in the first place (specifically as a response to what I said). ​

I feel like you're going back and forth between valuing subjective data and objective data here. If you don't want to listen to the objective science (Binding affinities et cetera) and you don't want to listen to the subjective reports of others, what do you want to listen to? Your own opinion? (which seems to be that people are conspiring against DXM)

What degree and frequency of these seizures are you talking about? I always thought that Using any Excitatory drugs (Cannabinoid agonists, Serotonergic Psychedellics, Amphetamines, Anti Muscarinics, Dissociatives etc) Lowered the seizure threshold anyways. Also you're wrong on the reason why Ketamine is used in Anesthesia more than Dextromethorphan. The reason why Ketamine is used more as an anesthetic is because of the fact that Ketamine suppresses breathing less than other dissociatives which otherwise could be a problem considering the Sedative cocktails commonly used in General anesthetic preparations.​

There are many emergency situations where the seizure threshold is already low. Giving somebody an NRI in that situation isn't the best idea.

I understand that another reason why ketamine is used in emergency situations is because it doesn't depress breathing - if you actually read what I wrote carefully I never excluded that as a reason... It just wasn't related to the differences of DXM and ketamine (which is what I was discussing).

"I was referring to the lowered seizure threshold as a reason as to why you won't see DXM prescribed in emergency situations as an anesthetic"

You'll see I wrote "a reason" not "the reason", so it seems to me at this point you either didn't read what I wrote carefully or didn't care and are just trying to win an argument? Either way I feel as though I'm wasting my time

Lol, when did I ever say that all reports of DXM's negative effects were related to what you or I mentioned? Another strawman. The simple point that you still seem to be missing is that the MAJORITY of these reports correlate to bad planning, enzymatic deficiencies, and 3rd person influence (Propaganda, elitism, condescension of the majority of the users of dxm). Very little of these reports use actual data to come to the correct conclusion of why Dextromethorphan can be a "problem."

I really don't think that there are a lot of "dirty drug" reports on DXM because of bad planning/liver issues/societal influence. I think its because it tends to have subjectively different effects than other NMDA antagonists, and if you can't accept that DXM has different effects from other NMDA antagonists then I don't know what to tell you. All drugs are different. DXM is clearly unique. Why is it hard to accept that DXM is different because of its pharmacology? Why does it have to be a societal influence thing?

 

[Cotcha Yankinov]

X11400, I am going to go out on a limb here and say you've never taken ketamine.

I've been tempted to ask this whole time what dissos that they have to compare subjectively here

 

[X11400]

You originally introduced the term "dirty" into this discussion: "But what about dxm? It's commonly described as being dirty by the people who hate on it."

I have to say that the term "dirty" aptly describes how some people feel about it (including myself) relative to e.g. memantine and I can't think of a better cover-all term that those who have experienced the muddiness may connect with, thus I merely repeated the term dirty... There aren't really good objective measurements here so we have to rely on what we've got; subjective reports. Consciousness is something that is fundamentally subjective.. So how we would describe an experience fundamentally necessitates subjective terminology..

If you don't like the subjective reports, then what would you suggest we do to study the matter scientifically (seeing as you don't seem to be interested in the details of the pharmacology)?

Maybe objective measurements like:

"How often does the human head-twitch?"
"How quickly does the human scurry around their room?"
"How long does it take the human to find the submerged platform?"



The various side effects of DXM don't stop some people from revering the dextroverse as well. That doesn't mean that some people won't dislike either drug for whatever reason.

We can't just say "XYZ side effect that you get from that drug is all in your head - its just because of a preconceived notion about the drug, and the reason you don't feel that side effect from another drug in the same class is because you have different preconceived notions about that drug, not because of a difference in pharmacology."


I feel like you're going back and forth between valuing subjective data and objective data here. If you don't want to listen to the objective science (Binding affinities et cetera) and you don't want to listen to the subjective reports of others, what do you want to listen to? Your own opinion? (which seems to be that people are conspiring against DXM)


There are many emergency situations where the seizure threshold is already low. Giving somebody an NRI in that situation isn't the best idea.

I understand that another reason why ketamine is used in emergency situations is because it doesn't depress breathing - if you actually read what I wrote carefully I never excluded that as a reason... It just wasn't related to the differences of DXM and ketamine (which is what I was discussing).

"I was referring to the lowered seizure threshold as a reason as to why you won't see DXM prescribed in emergency situations as an anesthetic"

You'll see I wrote "a reason" not "the reason", so it seems to me at this point you either didn't read what I wrote carefully or didn't care and are just trying to win an argument? Either way I feel as though I'm wasting my time


I really don't think that there are a lot of "dirty drug" reports on DXM because of bad planning/liver issues/societal influence. I think its because it tends to have subjectively different effects than other NMDA antagonists, and if you can't accept that DXM has different effects from other NMDA antagonists then I don't know what to tell you. All drugs are different. DXM is clearly unique. Why is it hard to accept that DXM is different because of its pharmacology? Why does it have to be a societal influence thing?

I didn't even ask you this question originally so why do you even think that because I originally said "dirty" that it's even relevant? You literally followed my post just to try to debunk anything I say with your statements. You keep playing these mental gymnastics as if they prove your mostly subjective opinions on drugs (your sarcasm and condescension is unwarranted also). Anyways, if you expect me to care for this supposed pharmacological information, at least cite your statements because this is pure conjecture at this point (what is the pharmacological mechanism of action for "dirtiness?"). Also please cite me these supposed high incidences of seizures that you seem to keep repeating. Another question, Doesn't dopamine also lower the seizure threshold, and wouldn't anesthetic doses of ketamine cause high levels of dopamine to be released in the brain, and or inhibited from reabsorbtion into the synapse? You're still stuck on the oversimplification of drugs in which we as humans honestly do not fully understand yet. To be honest, I'm done here with this conversation as you aren't even contributing to it in a positive way at this point anyways.

 

[Cotcha Yankinov]

Followed your post? I check this neuroscience forum for new posts when I'm bored, and I did answer your original question by the way. The person you asked the question to hasn't been on this forum for quite a while so I didn't expect them to answer

Also please cite me these supposed high incidences of seizures that you seem to keep repeating. Another question, Doesn't dopamine also lower the seizure threshold, and wouldn't anesthetic doses of ketamine cause high levels of dopamine to be released in the brain, and or inhibited from reabsorbtion into the synapse?

I've never actually said anything about high rates of seizures with DXM so once again you're misrepresenting what I'm saying. I really just said that DXM/SNRI can lower the seizure threshold. There are epilepsy patients whose seizures improve with SSRIs/SNRIs but there are also patients who worsen on SSRIs/SNRIs https://www.ncbi.nlm.nih.gov/pubmed/8000717/

NMDA antagonism would be expected at some doses to raise the seizure threshold (there are cases where NMDA antagonists can treat epilepsy) however there will come a point where any NMDA antagonist will induce seizures, regardless of its off-target effects. Depending on if one NMDA antagonist has more NE/5-HT reuptake inhibition properties or if the PK factors are weird like with DXM, during the titrating phase or on the excretion phase the seizure threshold could be lowered. But that's obviously not the only reason why ketamine anesthesia is preferable to... DXM anesthesia

 

[dood42069]

I've never actually said anything about high rates of seizures with DXM so once again you're misrepresenting what I'm saying. I really just said that DXM/SNRI can lower the seizure threshold. There are epilepsy patients whose seizures improve with SSRIs/SNRIs but there are also patients who worsen on SSRIs/SNRIs

NMDA antagonism would be expected at some doses to raise the seizure threshold (there are cases where NMDA antagonists can treat epilepsy) however there will come a point where any NMDA antagonist will induce seizures, regardless of its off-target effects. Depending on if one NMDA antagonist has more NE/5-HT reuptake inhibition properties or if the PK factors are weird like with DXM, during the titrating phase or on the excretion phase the seizure threshold could be lowered. But that's obviously not the only reason why ketamine anesthesia is preferable to... DXM anesthesia

Yeah, the chances of getting a seizure with DXM are from slim to none unless you take it with SSRIs or MAO inhibitors or sertogenic drugs. I personally love the feeling of DXM. It is a really fucking weird drug lol.