Antidepressant effects of DXM and other dissociatives compared to ketamine

[X11400]

It's a fact that some people experience severe bladder and kidney issues from ketamine usage... it really is quite surprising that a doctor would prescribe that amount every day for such a long time. If you haven't exprienced issues yet that's a good sign, but there are all sorts of case studies, it's not just ketamine either but any arylcyclohexylamine. To try to pretend it's not a concern would be to brush a lot of peoples' experiences under the rug.

To the OP, eventually you will get a much higher tolerance, which you seem to have done. The only way to get high again is to take a break or increase the dosage.

So you specified arylcyclohexlamines so can I infer from that assertion that dextromethorphan doesn’t have these issues? Can I also ask why dextromethorphan isn’t being used for this antidepressant purpose like ketamine is?

 

[Vastness]

^ Dextromethorphan does not, no, bladder damage is an arylcyclohexylamine thing. However it's also a much dirtier drug with the potential to be a lot more harmful in other ways, and with a much lower lethal dose relative to the recreational dose than ketamine, which is likely one of the main reasons it hasn't been studied for the antidepressant effect. It's also important to note that the antidepressant effect, as far as we know right now, is not a dissociative thing, and it may not even be an arylcyclohexylamine thing - as far as there being research to back it up, it's strictly a ketamine thing. A similar effect might be present in other dissociatives but the research just isn't there to show it, and the exact mechanism of the effect is not entirely understood even with ketamine, so for now it's a complete unknown whether even other arylcyclohexylamines would have a similar antidepressant effect, let alone other non-ACH dissociatives.

 

[X11400]

^ Dextromethorphan does not, no, bladder damage is an arylcyclohexylamine thing. However it's also a much dirtier drug with the potential to be a lot more harmful in other ways, and with a much lower lethal dose relative to the recreational dose than ketamine, which is likely one of the main reasons it hasn't been studied for the antidepressant effect. It's also important to note that the antidepressant effect, as far as we know right now, is not a dissociative thing, and it may not even be an arylcyclohexylamine thing - as far as there being research to back it up, it's strictly a ketamine thing. A similar effect might be present in other dissociatives but the research just isn't there to show it, and the exact mechanism of the effect is not entirely understood even with ketamine, so for now it's a complete unknown whether even other arylcyclohexylamines would have a similar antidepressant effect, let alone other non-ACH dissociatives.

By “dirtier” what exactly do you mean? I thought all of these stimulatory dissociatives had Antidepressant properties mediated by dopaminergic and serotonergic actions. I am by no means a proponent of dextromethorphan but let us please refrain from using such colloquialisms when we’re trying to explain the complex pharmacologies of dissociatives. Using words like that are quite counterproductive if one is trying to learn actual pharmacology.

Edit: I haven’t even seen any established lethal dosages for ket or dxm so please cite your claims.

 

[Vastness]

"Dirty" is a pharmacological term, if, admittedly, an "informal" one, as Wikipedia phrases it:

In pharmacology, a dirty drug is an informal term for drugs that may bind to many different molecular targets or receptors in the body, and so tend to have a wide range of effects and possibly adverse drug reactions. Today, pharmaceutical companies try to make new drugs as selective as possible to minimise binding to antitargets and hence reduce the occurrence of side effects and risk of adverse reactions.

Examples of compounds often cited as "dirty drugs" include tramadol, chlorpromazine, olanzapine, dextromethorphan and ibogaine, all of which bind to multiple receptors or influence multiple receptor systems.

Amusingly, dextromethorphan as you can see is actually listed as a prime example of a "dirty drug".

I thought all of these stimulatory dissociatives had Antidepressant properties mediated by dopaminergic and serotonergic actions.

Why would you think this? Dissociation is not a medically desired state, thus the majority of dissociatives that are also in medical usage have not been studied for their psychiatric effects. The ones that are not used medically have barely been studied at all.

I haven’t even seen any established lethal dosages for ket or dxm so please cite your claims.

This information is readily available everywhere. The Erowid DXM dosage page puts a "Risk of Death" dose between 2,500 - 20,000mg. Note the extremely wide range and how close this is to the "Heavy" recreational dose range which tops out at 1500mg. I won't bother to link you to the ketamine dosage page but recreational dosages of ketamine are known to be around 250-500mg at the higher end, which is still well below the usual anaesthetic dose used in medical settings, and the lethal dose of ketamine is not even known, it's widely known to be a very safe substance - when speaking in terms of acute toxicity from a single dose.

 

[X11400]

By “dirtier” what exactly do you mean? I thought all of these stimulatory dissociatives had Antidepressant properties mediated by dopaminergic and serotonergic actions. I am by no means a proponent of dextromethorphan but let us please refrain from using such colloquialisms when we’re trying to explain the complex pharmacologies of dissociatives. Using words like that are quite counterproductive if one is trying to learn actual pharmacology.

"Dirty" is a pharmacological term, if, admittedly, an "informal" one, as Wikipedia phrases it:Amusingly, dextromethorphan as you can see is actually listed as a prime example of a "dirty drug".

Why would you think this? Dissociation is not a medically desired state, thus the majority of dissociatives that are also in medical usage have not been studied for their psychiatric effects.

This information is readily available everywhere. The Erowid DXM dosage page puts a "Risk of Death" dose between 2,500 - 20,000mg. Note the extremely wide range and how close this is to the "Heavy" recreational dose range which tops out at 1500mg. I won't bother to link you to the ketamine dosage page but recreational dosages of ketamine are known to be around 250-500mg at the higher end, which is still well below the usual anaesthetic dose used in medical settings, and the lethal dose of ketamine is not even known, it's widely known to be a very safe substance - when speaking in terms of acute toxicity from a single dose.

Yeah we know that “dirty” is an informal pharmacological terminology however, I’m struggling to find many chemicals which are entirely selective ligands. It is a common misconception that ketamine is less pharmacologically promiscuous than dextromethorphan. Also, 2.5 grams to 20 grams is still a pretty high therapeutic index. If you want, I can use basic ass Wikipedia to substantiate my claim on both ketamine and dextromethorphan being pharmacologically promiscuous. I also don’t think that it requires full dissociation in order for you to reap the antidepressive benefits of stimulatory dissociate anesthetics.

 

[Vastness]

I have moved this discussion to a new thread so as not to keep derailing the OP's original topic.

On what are you basing the idea that it is a "common misconception" that dextromethorphan is dirtier than ketamine?

As far as a "pretty high" therapeutic index, that is pretty relative. It seems unarguable that the therapeutic index of ketamine is far higher than that of dextromethorphan, and there are plenty of deaths and other complications resulting from the latter to back this up. If you want to argue otherwise, be my guest, but please do substantiate your claims somehow, I won't judge you for using wikipedia to do so.

I also don’t think that it requires full dissociation in order for you to reap the antidepressive benefits of stimulatory dissociate anesthetics.

Probably not - if there are indeed any antidepressant benefits to be reaped. Again, ketamine is the only dissociative with any evidence to indicate such properties (to my knowledge), and full dissociation does not seem to be required for these properties to become apparent. Other dissociatives might have similar properties - but at the moment, there is no evidence to support this. If you have any reason to think otherwise, again, please do share. Wikipedia is permissible.

 

[X11400]

First I would like to know how the post was derailed considering I was talking about he same topic.

 

[Vastness]

The OP's post was about reduced effectiveness of a medically prescribed dose of ketamine for pain.

Your own discussion has been exclusively about the potential antidepressant benefits of dextromethorphan and other dissociatives.

The fact that you are both talking about ketamine is not enough to make it "the same topic".

 

[tired of crap]

I lost all connections some time during my alcoholism. And not being techsavvy, when I ventured back to psychedelics in hopes that they’d both help with my depression and addiction I only had what was available to me.

LSD And mushrooms failed to provide any lasting relief for my depression but did allow for me to revisit “new” thoughts surrounding my substance abuse. But I always returned to drinking.

Aware of the trials utilizing ketamine I also wondered if dxm May exhibit similar properties. I was aware of it’s rather “dirty” receptor profile but given many different psychedelics including 5 men dmt, mushrooms /psilocybin and ayahuasca have all been mentioned, if not studied, for their antidepressant aspects I figured wth

And tbh I’m glad I did
Dxm provided me with relief from my depression lasting many more times that of lad and mushrooms... never mind the 2cs or M.

Given depression is rather multifaceted I’m not surprised that so many different psychedelics/disassociates are purported to alleviate depression.

To me though the studies which claim “after a single session” seem rather ah hopeful lol ... to me it took many experiences and a lifestyle change to turn things around for good ... or at least substantially better. The whole idea that psychedelics/arylcyclohexlamines or drugs at all can be a panacea seems absurd

 

[ChemicallyEnhanced]

I can see it with DXM. It actually hits me like an amphetamine for 4-5 hours. I'm usually just reading* and the next thing I know I'm racing through the pages for 4 hours straight like it's the best thing I've ever read.
Then comes the dissociation and things like stairs becoming FUCKING IMPOSSIBLE to navigate (I went to a bookstore with my parents while on a DXM binge an just bending down to the bottom shelves and then "climbing" back up was so HARD...if you've been in 2nd plateau ya'll know what I mean). I prefer the next-day afterglow to the actual high TBH. "Afterglow" is the right word because I feel happy and like I'm glowing.


*Yeah, I'm a loser and READ on drugs sometimes. Even high dose IV morphine/heroin every 2 hours I can still read a book a day and take it in somehow, Alcohol and benzo's are the only things I can't read on. I even like the read on psychedelics..except I'm not really reading because random movies and TV show episodes are playing on the page instead of words.

 

[tired of crap]

I never got to try ketamine during those times... but I was always about large doses myself in my previous use lol ... it had been likely >3 years since I had any disssos tho so nmda tolerance was relatively low (unless all the booze counts?)

Single trips never really provided me much relief either until I tried dxm. And I never got into microdosing (L/mushrooms) as I’d much prefer saving my tolerance for macro doses.

Of note, when I say lasting relief I mean about 2-3 weeks, sometimes waiting 4-6 weeks, supplementing with another pyschedelic or high dose edibles in the off weeks.

Given the results of these first few (6?) months I felt compelled to dose more and more frequently as I eventually lost the magic. By the end of the year sure I’d wait a month between doses but sometimes I’d dose all weekend... only for it to exasperate my anxiety and to a lesser extent my depression, in some sort of rebound (in comparison to the high). I’d become anxious af in the following days where I used to feel great relief for weeks

What helped?
Implementing the realizations all the tripping provided and slowing down with the drugs lol

 

[X11400]

^ Dextromethorphan does not, no, bladder damage is an arylcyclohexylamine thing. However it's also a much dirtier drug with the potential to be a lot more harmful in other ways, and with a much lower lethal dose relative to the recreational dose than ketamine, which is likely one of the main reasons it hasn't been studied for the antidepressant effect. It's also important to note that the antidepressant effect, as far as we know right now, is not a dissociative thing, and it may not even be an arylcyclohexylamine thing - as far as there being research to back it up, it's strictly a ketamine thing. A similar effect might be present in other dissociatives but the research just isn't there to show it, and the exact mechanism of the effect is not entirely understood even with ketamine, so for now it's a complete unknown whether even other arylcyclohexylamines would have a similar antidepressant effect, let alone other non-ACH dissociatives.

Why did you respond to my post in the first place when I directed my op to @Xorkoth?

 

[X11400]

I never got to try ketamine during those times... but I was always about large doses myself in my previous use lol ... it had been likely >3 years since I had any disssos tho so nmda tolerance was relatively low (unless all the booze counts?)

Single trips never really provided me much relief either until I tried dxm. And I never got into microdosing (L/mushrooms) as I’d much prefer saving my tolerance for macro doses.

Of note, when I say lasting relief I mean about 2-3 weeks, sometimes waiting 4-6 weeks, supplementing with another pyschedelic or high dose edibles in the off weeks.

Given the results of these first few (6?) months I felt compelled to dose more and more frequently as I eventually lost the magic. By the end of the year sure I’d wait a month between doses but sometimes I’d dose all weekend... only for it to exasperate my anxiety and to a lesser extent my depression, in some sort of rebound (in comparison to the high). I’d become anxious af in the following days where I used to feel great relief for weeks

What helped?
Implementing the realizations all the tripping provided and slowing down with the drugs lol

Yeah, tripping on anything consistently can be detrimental to ones psyche.

 

[X11400]

I can see it with DXM. It actually hits me like an amphetamine for 4-5 hours. I'm usually just reading* and the next thing I know I'm racing through the pages for 4 hours straight like it's the best thing I've ever read.
Then comes the dissociation and things like stairs becoming FUCKING IMPOSSIBLE to navigate (I went to a bookstore with my parents while on a DXM binge an just bending down to the bottom shelves and then "climbing" back up was so HARD...if you've been in 2nd plateau ya'll know what I mean). I prefer the next-day afterglow to the actual high TBH. "Afterglow" is the right word because I feel happy and like I'm glowing.


*Yeah, I'm a loser and READ on drugs sometimes. Even high dose IV morphine/heroin every 2 hours I can still read a book a day and take it in somehow, Alcohol and benzo's are the only things I can't read on. I even like the read on psychedelics..except I'm not really reading because random movies and TV show episodes are playing on the page instead of words.

Never got those effects that you describe however, we can both agree that both amphetamines and dxm are monoaminergic Stimulants.

 

[X11400]

The OP's post was about reduced effectiveness of a medically prescribed dose of ketamine for pain.

Your own discussion has been exclusively about the potential antidepressant benefits of dextromethorphan and other dissociatives.

The fact that you are both talking about ketamine is not enough to make it "the same topic".

Yeah you’re right, I was kind of on some bullshit for making that post on that thread considering I could have just made my own thread with the title that this one I’m currently posting on has, so my fault.

 

[ChemicallyEnhanced]

Never got those effects that you describe however, we can both agree that both amphetamines and dxm are monoaminergic Stimulants.

I think it's a very specific dosing. Very small doses cause slight drowsiness and then we all know about the plateaus. I think the amphetamine-like effect is first plateau maybe? I do get the dissociation at that dose but I also find it stimulating. Not like crack or meth but like a medium-low dose of amphetamine sulphate.

 

[X11400]

I think it's a very specific dosing. Very small doses cause slight drowsiness and then we all know about the plateaus. I think the amphetamine-like effect is first plateau maybe? I do get the dissociation at that dose but I also find it stimulating. Not like crack or meth but like a medium-low dose of amphetamine sulphate.

Yes sir, and not to sound like a dex head or wet head but that first plateau shit be right man lol.

 

[thegreenhand]

I've only done it once and it certainly had antidepressive effects. That said, it's probably not worth it just for that when ketamine has those effects as well. DXM is nauseating, disorienting, and quite frankly not enjoyable. At least for me. Given it's many side effects I can't see it ever being used medically for depression

 

[X11400]

I've only done it once and it certainly had antidepressive effects. That said, it's probably not worth it just for that when ketamine has those effects as well. DXM is nauseating, disorienting, and quite frankly not enjoyable. At least for me. Given it's many side effects I can't see it ever being used medically for depression

That’s a more reasonable explanation for why ketamine is more promising for the aforementioned purpose than dextromethorphan. The pharmacological promiscuity hypothesis is certainly lacking on that front.

 

[bamos]

Did anyone try low dosages of 3-HO-PCP? If I take it I usually take more than 5mg with benzos and opioids, but eventually it'll work as an antidepressant in dosages at about 0.5mg - dunno, but I'll try next month.
Although Tramadol is not a dissociative IME it works great as an antidepressant. The SSRI/SNRI effects of Tramadol kicks in 15 minutes after ingestion. I prefer the liquid form. If I take Tramadol, I do it rather because of the SSRI/SNRI effects and less because it's an opioid.
There are also psychiatric clinics in the EU where patients get it off-lable as an antidepressant. So you could give it a try if it doesn't interfere with your medication. I don't like Dextromethorphan because of it's nasty side effects. Sure Tramadol has side effects too, but if you take less than 200mg at once IME you'll be fine and if you haven't tried it before maybe start with 100mg just to be safe.