The worst thing about guaifenesin is there's also an ADHD medicine called "guanfacine" and if you take that everyone, including doctors, thinks you meant the other one.
You could say Tenex instead but it sounds like a telecom company.
Dextromethorphan tolerance builds so rapidly. I have found the withdrawal to be hell after taking it legitimately for a cold longer than I realized. I have tried SSRIs and found that they also have a synergetic effect with Bupropion (good medicine). SSRIs also make me drowsy, but at least they can be sustainably taken daily for months.
Sounds like me, except Vyvanse instead of Modafinol. Bupropion was the magic key. I thought my Vyvanse just wasn't working anymore.
Turns out I was just super depressed. Since switching meds I've lost a lot of weight because I don't have food cravings as much.
The way I think of it... Vyvanse keeps me focused when I get to work, but without Bupropion just getting out bed sometimes seems daunting. One gets me to start my day, the other keeps me focused when I do.
Does that lower the seizure threshold at all? (I've had docs get on my case about bupropion + mild other medication that can in theory impact the seizure threshold) But I'd be interested - potentially - in trying this combo as things are pretty cobwebby in the brain department lately.
The combination is known as AXS-05 in studies and will be marketed as Auvelity.
Interesting combo. Buproprion is an antidepressant by itself, but it also inhibits the enzymes that break Dextromethorphan down in the body. Taking the two drugs together is not equivalent to taking the same dose of Dextromethorphan alone because Bupropion induces a very different exposure to DXM and its metabolites. Ignore anyone who tries to compare this to recreational DXM consumption because they're quite different.
Dextromethorphan gets a lot of attention for being an NMDA antagonist, but fewer people know that it has quite strong affinity for the serotonin transporter (the primary affinity of SSRIs). It also has potentially significant affinity for the sigma-1 receptor, the norepinephrine transporter, and several other receptors that have been noted to be potentially useful for depression modulation.
In other words, this feels a little bit like a shotgun approach to poking a wide array of receptors that may or may not be helpful in modulating depressive disorders. I'd take some of the narratives about this being an "NMDA drug like ketamine" with a huuuge grain of salt.
People have been trying this combination for several years in DIY fashion (not recommended, but info is out there) since the original study came out. I've seen some reports of good results, other reports of weird side effects that interfered with daily activities. I wouldn't rush to characterize this as a miracle drug or a first-line treatment, but it does seem to help certain patients who haven't seen much benefit from previous drugs.
Also worth noting that other studies haven't been as overwhelmingly positive as this one. Axsome Therapeutics (company researching the drug) stumbled a few years ago when their own trial failed to show statistical significance for Bupropion+DXM over Bupropion alone. Later studies seem to have been more positive though.
Thank you for explaining the interaction that makes this work. I was very confused for a bit trying to understand how mixing a cough suppressant with an anti-depressant would change the chemistry to the extent highlighted in the study.
> Axsome Therapeutics (company researching the drug) stumbled a few years ago when their own trial failed to show statistical significance for Bupropion+DXM over Bupropion alone. Later studies seem to have been more positive though.
Not being familiar with pharma research, that makes me wonder where such differences in results would come from. Different dosages in different studies? Differences in other treatment parameters or modality? Differences in some kinds of chemical details despite the basic molecule being the same? Patient selection? Chance? P-hacking or something similar? The first trial failing to show an effect that does exist due to methodology?
True story, about a year ago, one of my doctors suggested I try this combination experimentally, since I was already taking bupropion and tolerating it well.
I didn't notice anything change in the few months I tried it, other than that I hated the taste of cough syrup even more.
(This is not intended to suggest that it proves or disproves anything other than that people are suggesting this be tried.)
Haven't tried it but Bupropion changed my life. SSRI's failed me. Couldn't tolerate any of them (ED, which made me more depressed). Bupropion + Vyvanse seems to make me eat less, work harder, stay focused longer and have less food cravings. Lost 50 pounds without dieting just from not eating junk food as often.
It's also very strange, as a drug. "Definitely not a stimulant, the list of effects and side effects just kind of looks like one, only drug in its class approved in the US, also approved for helping you quit smoking..."
>> once daily for the first 3 days and twice daily thereafter, for a total of 6 weeks
> Ignore anyone who tries to compare this to recreational DXM consumption because they're quite different.
Other promising trials for a fast acting treatment of treatment-resistant depression are using single doses up to 600mg of DXM. My personal experience is that a single dose of 600-900mg of dextromethorphan will cure depression like aspirin cures a headache, with the depression-suppressing effect lasting from a month up to 6 months and longer. The considerable side-effects of such a large dose are mitigated by 20mg of pepsid and allowing the sedative effects of DXM to sleep through the hallucinations, delusions, susceptibility to suggestion, etc.
But we'll leave it to pharmaceutical companies to develop a patentable formula that requires the patient to take pills for the rest of their lives. Imagine if headaches were treated the same way. This ubiquitous ideology of permanently medicating mental health patients is nothing less than the commercialism of mental illness. Patients are being farmed by Big Pharm.
There is a widespread stigma in medicine and society at large against self-medicating and specifically against using DXM to treat depression, due to its abuse by 14-year-olds and drug cowboys. I've only quoted you to remind you of same and that dosages of DXM in comparison to other pharmaceuticals is entirely arbitrary (for example, aspirin bottles indicate 650mg for a headache). The lethal dose of DXM is an estimation because, as of yet, no one has managed to achieve a fatal overdose of DXM. So it is a safe drug, and because it has been off patent since the 1950's, we're not going to see any ordinary unadulterated formulations. Lucky thing, DXM is not a controlled substance.
Robitussin is not dextromethorphan in the same way that beer is not alcohol. I'm not aware of any formula of Robitussin that doesn't include other drugs that are dangerous at high doses, including probable damage to kidneys and liver. Overdosing on Robitussin is an astoundingly bad idea.
FWIW, I'm sick and am currently looking at a bottle of Robitussin Dry Cough Forte, and the only active ingredients are DXM. But yes, if you're wanting to do high doses, tablets are gonna be the least unpleasant option
That's because, as far as it exists, America's nanny-state sucks, (the secondary drug ingredients have a dual purpose of treating some other ailment beyond cough, such as chest congestion, and dissuading from intentional medicative overdose), and you're probably D&U.
Agreed on the nanny-state bit, but we kind of get what we deserve since most people are ok with "protecting" us from dangerous drugs. Except for alcohol and tobacco, those get a pass for $ome rea$on.
At least cannabis is making it's way into normality and states are recognizing that there's money to be made.
All of the dissociative drugs likely have this effect, and likely by a common mechanism. Single-dose ketamine can have similar results.
Unlike with ongoing low-dose dissociatives (which are more likely acting like a classic antidepressant), I suspect the strong single-dose effect is from cognitive changes that occur during the dissociative episode. It's oddly easy to look (metaphorically or literally) at things that would normally make you flinch (metaphorically or literally). As I once heard it put, you can only die so many times during the trip before you stop worrying about it.
I am still inclined to a slightly more cautious tone than your post; for example DXM dosing is very sensitive to body weight and 900 mg for a large man vs. small woman will be very different. At high doses it interacts highly unpleasantly, and potentially dangerously, with a number of drugs, including common antidepressants and ADHD medications. It even interacts strongly with grapefruit.
> All of the dissociative drugs likely have this effect, and likely by a common mechanism. Single-dose ketamine can have similar results.
I am only aware of 5 dissociatives: Dextromethorphan, Nitrous oxide, Ketamine, Phencyclidine, and Dimethyltryptamine. I have no idea if all or any of them would be effective at treating depression other than Dextromethorphan and Ketamine. Only Dextromethorphan is readily and legally available without a prescription. While Ketamine has promising results, between the time depression stikes and the date of a Ketamine clinic appointment, sudden death can occur. I'm certainly not telling anyone what to do, but from personal experience, clinical depression sucks and it kills. When facing a 6 week to 3 month delay in even getting a Ketamine clinic appointment, or just a PMH-NP appointment for a more ordinary antidepressent, it is infinitely easier and more comfortable to accept furtive looks at any of the local drug stores and know that by the following morning depression will be gone.
> Unlike with ongoing low-dose dissociatives (which are more likely acting like a classic antidepressant), I suspect the strong single-dose effect is from cognitive changes that occur during the dissociative episode.
I'm not sure cognition exists while asleep, nor if sleeping through a dose can be considered a dissociative "episode." But I do know that dextromethorphan at the doses I mentioned has an irresistible sedative effect, and falling asleep is inevitable, short of taking stimulants.
> It's oddly easy to look (metaphorically or literally) at things that would normally make you flinch (metaphorically or literally). As I once heard it put, you can only die so many times during the trip before you stop worrying about it.
That is clever, but tripping is recreational and neither it nor consciousness is necessary to curing depression with dextromethorphan.
> I am still inclined to a slightly more cautious tone than your post; for example DXM dosing is very sensitive to body weight and 900 mg for a large man vs. small woman will be very different.
This is a very good point, and the dosages mentioned can be considered for average weight and for average depressions. Whether heavier individuals and deeper depressions require larger doses, or with lower than average weight that lower doses will still be effective, I really cannot say, but it seams reasonable.
> At high doses it interacts highly unpleasantly, and potentially dangerously, with a number of drugs, including common antidepressants and ADHD medications. It even interacts strongly with grapefruit.
This is a very good point and mixing any dose of DXM with any other SSRI and even St. Johns Wart could cause Serotonin Syndrome, which can be fatal, but is definitely painfully unpleasant. Grapefruit contains compounds known as furanocoumarins which block CYP3A4 enzymes, reducing the body's ability to break down drugs. Drug blood levels may rise, resulting in a risk of heightened side effects. But I think you'd have to consume a lot of grapefruit or its juice for this to become a serious problem. I can't say for sure because its not in my diet. The OTC antacid drug cimetidine has the same mechanism, but because dosages are concentrated in a pill, the effect can be far greater.
(Tangent) A lot of drugs have issues with grapefruit, in that grapefruit inhibits enzymes (e.g., CYP1A2) which the body uses to metabolize said drug. Most commonly, the grapefruit juice would cause inadvertent drug overdoses as the drug won’t otherwise be processed and simply continue to circulate.
> Focusing on fatalities and LD50 is a red herring in drug safety.
LD50 is ordinarily used as a measure of toxicity. In general, the smaller the LD50 value, the more toxic a substance is. The opposite is also true: the larger the LD50 value, the lower the toxicity. I don't believe it is beyond the realm of reason that, in general, the more toxic something is, the more lethal it will be. Your claim could be considered a red herring. Being that I neither focused on nor made any mention of fatalities, LD50, nor the field of drug safety, your comment is also a straw man.
What I instead argued was that dxm, and only dxm, can be considered safe because it is an old drug (went off patent in the 1950's, leaving lots of time for plenty of safety trials, scientific and amateur), it is OTC (implicitly it has been tested and scrutinized for safety by the FDA at various dosages and been approved to have no scheduled controls), and the lethal dose is an estimation (being that it is so old and readily available without prescription, and drug abusers without restraint have survived all imaginable overdoses), which only taken together support my claim that DXM is safe, specifically, what I meant was that DXM is forgiving of mistakenly high dosages in a way that other OTC drugs, such as Acetaminophen, Diphenhydramine, and even Aspirin, are not.
> There are many drugs that can do a lot of damage at doses far lower than those that kill someone.
This is a bandwagon argument. You're implicitly arguing fallaciously that because there are "many drugs" that can produce significant damage at doses much lower than a lethal dose, then this is also true of dextromethorphan.
>> There are many drugs that can do a lot of damage at doses far lower than those that kill someone.
> This is a bandwagon argument. You're implicitly arguing fallaciously that because there are "many drugs" that can produce significant damage at doses much lower than a lethal dose, then this is also true of dextromethorphan.
This is more like Pascal's wager - better don't mess with what you can't understand or see. Personality, memories, beliefs, goals, fears.
Anecdotally I lost a portion of my memory and cognitive skills after a kind of flu. Instead of support, I've been met mostly with claims that I'm making it up or I am acting like a hypochondriac. All while I struggled to re-learn how to use my daily driver Linux system and where important things are.
> Anecdotally I lost a portion of my memory and cognitive skills after a kind of flu. Instead of support, I've been met mostly with claims that I'm making it up or I am acting like a hypochondriac.
It sucks that many working in medicine are suspicious, paranoid and lack empathy. Sorry for your troubles. Consider taking niacin or B complex supplements.
> LD50 is ordinarily used as a measure of toxicity.
LD50 is literally "median lethal dose". LD = lethal dose and 50 for median.
It doesn't tell you anything about toxicities that aren't fatal.
There are many, many drugs that will do life-altering damage at doses that won't kill 50% of people (or 50% of lab rats). Nobody should be using LD50 to gauge toxicity.
> It doesn't tell you anything about toxicities that aren't fatal.
Though LD50, or median lethal dose, is defined as the dose of a test substance that is lethal for 50% of the animals in a dose group, a substance with small LD50 value will necessarily be more toxic than a substance with a much larger LD50 value. In spite of this, I have made no argument regarding LD50 or fatalities, and certainly haven't focused on them. You introduced this in your previous comment as a straw man and continue unabated here in fallacious argument.
> There are many, many drugs that will do life-altering damage at doses that won't kill 50% of people (or 50% of lab rats).
This is irrelevant unless it is also true for dextromethorpan, which it is not. To argue that certain drugs with high toxicity but low lethality somehow affects those same measures of dextromethorphan is a bandwagon argument and a sweeping generalization.
> Nobody should be using LD50 to gauge toxicity.
What, then, is the gauge for toxicity that stands in stark contradiction to LD50? LD50 is regularly and ordinarily used as a measure of toxicity and acute toxicity, and use of LD50 in this way is not remotely exceptional. Toxicity and lethality are closely related. The more toxic something is, the more lethal it is at higher doses. If these highly toxic drugs aren't killing patients or lab rats fast enough for your definition of lethal, nevertheless, the more damage done to tissue, organs and bodily systems, the shorter the life span.
Regardless of the level of accuracy of your technical knowledge, you introduced an argument that is not my argument only to attack it, and I have now entertained your straw man twice.
I worry this comment is overly dismissive of criticisms and overly optimistic about potential positives. On medicine topics I think it is important to try remain objective.
1. On DXM being an NMDA antagonist:
At high concentration DXM is an NMDA antagonist and AXS-05 does dramatically increases DXM concentration [0] (slide 6). It is not clear to me why we should "ignore anyone" who makes this comparison?
2. On AXS-05 having a wide array of receptor targets:
Almost all psychoactive drugs have some affinity for many receptors (just wikipedia any anti-psychotic e.g. [1]). Are any of the targets mentioned clinically significant at therapeutic concentrations?
> It is not clear to me why we should "ignore anyone" who makes this comparison?
I said that we should ignore people trying to compare this drug to recreational use.
It's likely that NMDA is in play and I'm not suggesting otherwise. I wanted to highlight that DXM has significant affinities for other targets like the serotonin transporter that could also explain the efficacy, so it's a mistake to focus on one receptor as the single answer.
I know a therapist that’s interested in ketamine/psilocybin therapy and when she asked me about these types of drugs, I immediately told her that DXM is hands down obviously going to have clinical use.
Unable to access the full paper at the moment, but curious if they addressed the fact that Bupropion can take 6-8wks before symptoms such as depressed mood or anhedonia are affected. Were these bupropion naïve patients? From the abstract, this was only a 6wk study - which means that the bupropion may not yet have been working at maximal efficacy for those in the bupropion group during the study period and therefore of course the AXS would show a benefit when compared to only bupropion
Delysm is Dextromethorphan Polistirex which is a time-release form of DXM. I don't think it lets you get the same peaks / thresholds as 'instant release' dextromethorphan.
You could probably still do that. Or claim an allergy to the additives in Delsym (a corn allergy is a good one because corn is in everything) and ask to get a pure dextromethorphan formulation from a compounding pharmacy.
Special note for anyone considering messing with the stuff: If you are on SSRIs or MAOIs, it can literally kill you, so be careful and do your homework.
The big grain of salt for all depression treatments is that depression is a "wastebasket diagnosis". The only real distinction available between numerous pathologies is what medication seems to help them.
This means any group of patients diagnosed and not treated yet will have a grab bag of different actual pathologies. Whatever thing you try might help a few, make a few others worse, and have no effect on the rest.
This is why we keep seeing reports that antidepressants "don't work".
If the patients in this study were already on bupropion, that has narrowed the field and can explain the difference from others. It doesn't mean DXM is much better than others, it just means it has been better targeted.
You can think of a regular RCT of an antidepressant as if it were checking whether splinting the lower legs is good for trauma victims who come in with all kinds of broken bones -- arms, legs, clavicles. In the RCT, everybody gets their lower legs splinted.
Of course only the patients who broke a shinbone benefit.
So if this trial pre-selects people on bupropion, it would be like splinting shins only of people with leg injuries. You still miss on the femur, knee, and ankle patients, but the odds of a hit are better.
Validity of RCTs depends utterly on reliable and specific diagnosis. It is very easy for an RCT to go wrong. Treating them as automatically right is like treating any other experiment as automatically right. Calling RCTs "the Gold Standard" blinds us to its failures.
60 comments
[ 2.8 ms ] story [ 143 ms ] threadWho knew that "more tussin" would be the answer?
You could say Tenex instead but it sounds like a telecom company.
Turns out I was just super depressed. Since switching meds I've lost a lot of weight because I don't have food cravings as much.
The way I think of it... Vyvanse keeps me focused when I get to work, but without Bupropion just getting out bed sometimes seems daunting. One gets me to start my day, the other keeps me focused when I do.
It's nothing like taking high doses of DXM alone for recreational purposes.
Lean is codeine syrup, a pain killer.
DXM is totally different. Just because they are both used for treating cough doesn’t mean their pathways are the same.
Interesting combo. Buproprion is an antidepressant by itself, but it also inhibits the enzymes that break Dextromethorphan down in the body. Taking the two drugs together is not equivalent to taking the same dose of Dextromethorphan alone because Bupropion induces a very different exposure to DXM and its metabolites. Ignore anyone who tries to compare this to recreational DXM consumption because they're quite different.
Dextromethorphan gets a lot of attention for being an NMDA antagonist, but fewer people know that it has quite strong affinity for the serotonin transporter (the primary affinity of SSRIs). It also has potentially significant affinity for the sigma-1 receptor, the norepinephrine transporter, and several other receptors that have been noted to be potentially useful for depression modulation.
In other words, this feels a little bit like a shotgun approach to poking a wide array of receptors that may or may not be helpful in modulating depressive disorders. I'd take some of the narratives about this being an "NMDA drug like ketamine" with a huuuge grain of salt.
People have been trying this combination for several years in DIY fashion (not recommended, but info is out there) since the original study came out. I've seen some reports of good results, other reports of weird side effects that interfered with daily activities. I wouldn't rush to characterize this as a miracle drug or a first-line treatment, but it does seem to help certain patients who haven't seen much benefit from previous drugs.
Also worth noting that other studies haven't been as overwhelmingly positive as this one. Axsome Therapeutics (company researching the drug) stumbled a few years ago when their own trial failed to show statistical significance for Bupropion+DXM over Bupropion alone. Later studies seem to have been more positive though.
Not being familiar with pharma research, that makes me wonder where such differences in results would come from. Different dosages in different studies? Differences in other treatment parameters or modality? Differences in some kinds of chemical details despite the basic molecule being the same? Patient selection? Chance? P-hacking or something similar? The first trial failing to show an effect that does exist due to methodology?
I didn't notice anything change in the few months I tried it, other than that I hated the taste of cough syrup even more.
(This is not intended to suggest that it proves or disproves anything other than that people are suggesting this be tried.)
It's also very strange, as a drug. "Definitely not a stimulant, the list of effects and side effects just kind of looks like one, only drug in its class approved in the US, also approved for helping you quit smoking..."
> Ignore anyone who tries to compare this to recreational DXM consumption because they're quite different.
Other promising trials for a fast acting treatment of treatment-resistant depression are using single doses up to 600mg of DXM. My personal experience is that a single dose of 600-900mg of dextromethorphan will cure depression like aspirin cures a headache, with the depression-suppressing effect lasting from a month up to 6 months and longer. The considerable side-effects of such a large dose are mitigated by 20mg of pepsid and allowing the sedative effects of DXM to sleep through the hallucinations, delusions, susceptibility to suggestion, etc.
But we'll leave it to pharmaceutical companies to develop a patentable formula that requires the patient to take pills for the rest of their lives. Imagine if headaches were treated the same way. This ubiquitous ideology of permanently medicating mental health patients is nothing less than the commercialism of mental illness. Patients are being farmed by Big Pharm.
There is a widespread stigma in medicine and society at large against self-medicating and specifically against using DXM to treat depression, due to its abuse by 14-year-olds and drug cowboys. I've only quoted you to remind you of same and that dosages of DXM in comparison to other pharmaceuticals is entirely arbitrary (for example, aspirin bottles indicate 650mg for a headache). The lethal dose of DXM is an estimation because, as of yet, no one has managed to achieve a fatal overdose of DXM. So it is a safe drug, and because it has been off patent since the 1950's, we're not going to see any ordinary unadulterated formulations. Lucky thing, DXM is not a controlled substance.
That's over a pint of Robitussun -- I couldn't imagine chugging that down. I am intrigued by your claim though.
I've never heard this term before, what does it mean
At least cannabis is making it's way into normality and states are recognizing that there's money to be made.
Unlike with ongoing low-dose dissociatives (which are more likely acting like a classic antidepressant), I suspect the strong single-dose effect is from cognitive changes that occur during the dissociative episode. It's oddly easy to look (metaphorically or literally) at things that would normally make you flinch (metaphorically or literally). As I once heard it put, you can only die so many times during the trip before you stop worrying about it.
I am still inclined to a slightly more cautious tone than your post; for example DXM dosing is very sensitive to body weight and 900 mg for a large man vs. small woman will be very different. At high doses it interacts highly unpleasantly, and potentially dangerously, with a number of drugs, including common antidepressants and ADHD medications. It even interacts strongly with grapefruit.
I am only aware of 5 dissociatives: Dextromethorphan, Nitrous oxide, Ketamine, Phencyclidine, and Dimethyltryptamine. I have no idea if all or any of them would be effective at treating depression other than Dextromethorphan and Ketamine. Only Dextromethorphan is readily and legally available without a prescription. While Ketamine has promising results, between the time depression stikes and the date of a Ketamine clinic appointment, sudden death can occur. I'm certainly not telling anyone what to do, but from personal experience, clinical depression sucks and it kills. When facing a 6 week to 3 month delay in even getting a Ketamine clinic appointment, or just a PMH-NP appointment for a more ordinary antidepressent, it is infinitely easier and more comfortable to accept furtive looks at any of the local drug stores and know that by the following morning depression will be gone.
> Unlike with ongoing low-dose dissociatives (which are more likely acting like a classic antidepressant), I suspect the strong single-dose effect is from cognitive changes that occur during the dissociative episode.
I'm not sure cognition exists while asleep, nor if sleeping through a dose can be considered a dissociative "episode." But I do know that dextromethorphan at the doses I mentioned has an irresistible sedative effect, and falling asleep is inevitable, short of taking stimulants.
> It's oddly easy to look (metaphorically or literally) at things that would normally make you flinch (metaphorically or literally). As I once heard it put, you can only die so many times during the trip before you stop worrying about it.
That is clever, but tripping is recreational and neither it nor consciousness is necessary to curing depression with dextromethorphan.
> I am still inclined to a slightly more cautious tone than your post; for example DXM dosing is very sensitive to body weight and 900 mg for a large man vs. small woman will be very different.
This is a very good point, and the dosages mentioned can be considered for average weight and for average depressions. Whether heavier individuals and deeper depressions require larger doses, or with lower than average weight that lower doses will still be effective, I really cannot say, but it seams reasonable.
> At high doses it interacts highly unpleasantly, and potentially dangerously, with a number of drugs, including common antidepressants and ADHD medications. It even interacts strongly with grapefruit.
This is a very good point and mixing any dose of DXM with any other SSRI and even St. Johns Wart could cause Serotonin Syndrome, which can be fatal, but is definitely painfully unpleasant. Grapefruit contains compounds known as furanocoumarins which block CYP3A4 enzymes, reducing the body's ability to break down drugs. Drug blood levels may rise, resulting in a risk of heightened side effects. But I think you'd have to consume a lot of grapefruit or its juice for this to become a serious problem. I can't say for sure because its not in my diet. The OTC antacid drug cimetidine has the same mechanism, but because dosages are concentrated in a pill, the effect can be far greater.
(Tangent) A lot of drugs have issues with grapefruit, in that grapefruit inhibits enzymes (e.g., CYP1A2) which the body uses to metabolize said drug. Most commonly, the grapefruit juice would cause inadvertent drug overdoses as the drug won’t otherwise be processed and simply continue to circulate.
Focusing on fatalities and LD50 is a red herring in drug safety.
There are many drugs that can do a lot of damage at doses far lower than those that kill someone.
LD50 is ordinarily used as a measure of toxicity. In general, the smaller the LD50 value, the more toxic a substance is. The opposite is also true: the larger the LD50 value, the lower the toxicity. I don't believe it is beyond the realm of reason that, in general, the more toxic something is, the more lethal it will be. Your claim could be considered a red herring. Being that I neither focused on nor made any mention of fatalities, LD50, nor the field of drug safety, your comment is also a straw man.
What I instead argued was that dxm, and only dxm, can be considered safe because it is an old drug (went off patent in the 1950's, leaving lots of time for plenty of safety trials, scientific and amateur), it is OTC (implicitly it has been tested and scrutinized for safety by the FDA at various dosages and been approved to have no scheduled controls), and the lethal dose is an estimation (being that it is so old and readily available without prescription, and drug abusers without restraint have survived all imaginable overdoses), which only taken together support my claim that DXM is safe, specifically, what I meant was that DXM is forgiving of mistakenly high dosages in a way that other OTC drugs, such as Acetaminophen, Diphenhydramine, and even Aspirin, are not.
> There are many drugs that can do a lot of damage at doses far lower than those that kill someone.
This is a bandwagon argument. You're implicitly arguing fallaciously that because there are "many drugs" that can produce significant damage at doses much lower than a lethal dose, then this is also true of dextromethorphan.
> This is a bandwagon argument. You're implicitly arguing fallaciously that because there are "many drugs" that can produce significant damage at doses much lower than a lethal dose, then this is also true of dextromethorphan.
This is more like Pascal's wager - better don't mess with what you can't understand or see. Personality, memories, beliefs, goals, fears.
Anecdotally I lost a portion of my memory and cognitive skills after a kind of flu. Instead of support, I've been met mostly with claims that I'm making it up or I am acting like a hypochondriac. All while I struggled to re-learn how to use my daily driver Linux system and where important things are.
It sucks that many working in medicine are suspicious, paranoid and lack empathy. Sorry for your troubles. Consider taking niacin or B complex supplements.
LD50 is literally "median lethal dose". LD = lethal dose and 50 for median.
It doesn't tell you anything about toxicities that aren't fatal.
There are many, many drugs that will do life-altering damage at doses that won't kill 50% of people (or 50% of lab rats). Nobody should be using LD50 to gauge toxicity.
Though LD50, or median lethal dose, is defined as the dose of a test substance that is lethal for 50% of the animals in a dose group, a substance with small LD50 value will necessarily be more toxic than a substance with a much larger LD50 value. In spite of this, I have made no argument regarding LD50 or fatalities, and certainly haven't focused on them. You introduced this in your previous comment as a straw man and continue unabated here in fallacious argument.
> There are many, many drugs that will do life-altering damage at doses that won't kill 50% of people (or 50% of lab rats).
This is irrelevant unless it is also true for dextromethorpan, which it is not. To argue that certain drugs with high toxicity but low lethality somehow affects those same measures of dextromethorphan is a bandwagon argument and a sweeping generalization.
> Nobody should be using LD50 to gauge toxicity.
What, then, is the gauge for toxicity that stands in stark contradiction to LD50? LD50 is regularly and ordinarily used as a measure of toxicity and acute toxicity, and use of LD50 in this way is not remotely exceptional. Toxicity and lethality are closely related. The more toxic something is, the more lethal it is at higher doses. If these highly toxic drugs aren't killing patients or lab rats fast enough for your definition of lethal, nevertheless, the more damage done to tissue, organs and bodily systems, the shorter the life span.
Regardless of the level of accuracy of your technical knowledge, you introduced an argument that is not my argument only to attack it, and I have now entertained your straw man twice.
1. On DXM being an NMDA antagonist: At high concentration DXM is an NMDA antagonist and AXS-05 does dramatically increases DXM concentration [0] (slide 6). It is not clear to me why we should "ignore anyone" who makes this comparison?
2. On AXS-05 having a wide array of receptor targets: Almost all psychoactive drugs have some affinity for many receptors (just wikipedia any anti-psychotic e.g. [1]). Are any of the targets mentioned clinically significant at therapeutic concentrations?
[0] https://axsometherapeuticsinc.gcs-web.com/static-files/4a508... [1] https://en.wikipedia.org/wiki/Olanzapine
I said that we should ignore people trying to compare this drug to recreational use.
It's likely that NMDA is in play and I'm not suggesting otherwise. I wanted to highlight that DXM has significant affinities for other targets like the serotonin transporter that could also explain the efficacy, so it's a mistake to focus on one receptor as the single answer.
I know a therapist that’s interested in ketamine/psilocybin therapy and when she asked me about these types of drugs, I immediately told her that DXM is hands down obviously going to have clinical use.
They definitely know that the people buying their products are using them to get high, some of their marketing in the past has been comical.
Back in my day, all the kids were cold-water extracting their paracetemol/Tylenol out of the combo pain reliever + cough suppressant medications: https://en.wikipedia.org/wiki/Cold_water_extraction
You could probably still do that. Or claim an allergy to the additives in Delsym (a corn allergy is a good one because corn is in everything) and ask to get a pure dextromethorphan formulation from a compounding pharmacy.
Freebase: https://www.amazon.com/RoboTablets-suppressant-Dextromethorp... (note: 130% HBr strength)
HBr Salt: https://www.amazon.com/RoboHBr-Cough-suppressant-Dextrometho...
Special note for anyone considering messing with the stuff: If you are on SSRIs or MAOIs, it can literally kill you, so be careful and do your homework.
This means any group of patients diagnosed and not treated yet will have a grab bag of different actual pathologies. Whatever thing you try might help a few, make a few others worse, and have no effect on the rest.
This is why we keep seeing reports that antidepressants "don't work".
If the patients in this study were already on bupropion, that has narrowed the field and can explain the difference from others. It doesn't mean DXM is much better than others, it just means it has been better targeted.
You can think of a regular RCT of an antidepressant as if it were checking whether splinting the lower legs is good for trauma victims who come in with all kinds of broken bones -- arms, legs, clavicles. In the RCT, everybody gets their lower legs splinted.
Of course only the patients who broke a shinbone benefit.
So if this trial pre-selects people on bupropion, it would be like splinting shins only of people with leg injuries. You still miss on the femur, knee, and ankle patients, but the odds of a hit are better.
Validity of RCTs depends utterly on reliable and specific diagnosis. It is very easy for an RCT to go wrong. Treating them as automatically right is like treating any other experiment as automatically right. Calling RCTs "the Gold Standard" blinds us to its failures.