Ketamine 'R' and 'S' Ketamine

[Axemancometh]

'R' isomer should really be called 'D-Ketamine' to keep up with the Latin but Scientists get dumber and dumber each year so whatever.

There's much debate (online, as far as I can tell) as to what really differentiates these two isomers of Ketamine: Many people believe (including whoever wrote the Wikipedia article) that the 'S-Ketamine' is significantly more potent than the 'R' isomer, which is supposedly a better general anaesthetic. I'll share what I've encountered in my experiences as I have had the privilege of doing *both* at points in time.

The 'S' feels like a retard-iffier drug - but at the same time it definitely is strong as fuck. It characteristically comes in little crystalline shards that must be crushed up (very satisfying) before you ingest. I snort some and consistently lose 50 IQ points and start drooling all over myself. It feels like I'm buzzing throughout my entire body but have a feerish state of mind. Reaching the 'K-hole' is very easy on this one which is not always a positive thing. You totally forget what time is becase you're so retarded you just focus on what your dog-like eyes are oriented towards. If you've never K-holed before, It best represents what Jacob Singer went through in Jacob's Ladder. (horrific dissocociative hallucinatory epxerience before you realise that you died ten years ago in the jungles of Vietnam - and this is the last gasp of your conciousness) Almost as if not more fucked than shroom-induced psychotic episode.

The 'R-Ketamine' is another story: Definitely much weaker so to speak, but I personally beleive is a much more accessable experience. This one looks like a big quartz rock that you have to smash up. I never felt like I was a true retard off this stuff - I could still have fun on this and realistically do things at the same time; what really does it for 'R' though is that all its 'trips' are inside your head. For example, the first time I did it it felt a hypnagogic dream where you swear that you turned off the lamp; or that you got up form the cough to wash your hands, while in reality you've been sitting still for the last ten minutes bobbing back and forth while your head feels like its doing summersaults in the void. You are definitely still smart enough to remember what time is, (or who and where you are) but it feels like it's drawn out tenfold and you'll start wondering if maybe you shouldn't have done this while you're supposed to be writing a paper. This was also my first Ket isomer which my boys were telling me was 'the trippier one' which I would somewhat stand by - but that is definitely a biased impression that I was given beforehand.

Now there's some people out there who also claim that all the 'R' or 'S' you get outside a lab/med facility is actually bullshit and that everything is always racemic all the time. I cannot on that, nor would I really agree wth that statement. However I am also not in any position to claim authority on this matter, so anything is possible unless proven otherwise. Any real Ketamine experts are welcome to chime in and grace the masses.

In conclusio; though 'S' Ketamine is definitely 'more powerful' than its right-handed sister, that is no indication that it is in any way 'better' and that the other is shit. 'R' Ket is friggin dope and a chill time and I would always reccomend it to anybody. Still no matter what always test your ket tho coz they're putting more bullshit like Xylazine and elephant-cock softener and whatnot in street score.

 

[KetWise]

I knew proper K addicts preferring R to "function" daily .

I think S is very good, good for tripping but it lacks this physical high that is interesting and doesnt last enough at some point.

Racemic is definitely available and I tend to think that I prefer it. They used to call it the 50/50. Liter times...

 

[crystalDeer]

'R' isomer should really be called 'D-Ketamine' to keep up with the Latin but Scientists get dumber and dumber each year so whatever.

There's much debate (online, as far as I can tell) as to what really differentiates these two isomers of Ketamine: Many people believe (including whoever wrote the Wikipedia article) that the 'S-Ketamine' is significantly more potent than the 'R' isomer, which is supposedly a better general anaesthetic. I'll share what I've encountered in my experiences as I have had the privilege of doing *both* at points in time.

The 'S' feels like a retard-iffier drug - but at the same time it definitely is strong as fuck. It characteristically comes in little crystalline shards that must be crushed up (very satisfying) before you ingest. I snort some and consistently lose 50 IQ points and start drooling all over myself. It feels like I'm buzzing throughout my entire body but have a feerish state of mind. Reaching the 'K-hole' is very easy on this one which is not always a positive thing. You totally forget what time is becase you're so retarded you just focus on what your dog-like eyes are oriented towards. If you've never K-holed before, It best represents what Jacob Singer went through in Jacob's Ladder. (horrific dissocociative hallucinatory epxerience before you realise that you died ten years ago in the jungles of Vietnam - and this is the last gasp of your conciousness) Almost as if not more fucked than shroom-induced psychotic episode.

The 'R-Ketamine' is another story: Definitely much weaker so to speak, but I personally beleive is a much more accessable experience. This one looks like a big quartz rock that you have to smash up. I never felt like I was a true retard off this stuff - I could still have fun on this and realistically do things at the same time; what really does it for 'R' though is that all its 'trips' are inside your head. For example, the first time I did it it felt a hypnagogic dream where you swear that you turned off the lamp; or that you got up form the cough to wash your hands, while in reality you've been sitting still for the last ten minutes bobbing back and forth while your head feels like its doing summersaults in the void. You are definitely still smart enough to remember what time is, (or who and where you are) but it feels like it's drawn out tenfold and you'll start wondering if maybe you shouldn't have done this while you're supposed to be writing a paper. This was also my first Ket isomer which my boys were telling me was 'the trippier one' which I would somewhat stand by - but that is definitely a biased impression that I was given beforehand.

Now there's some people out there who also claim that all the 'R' or 'S' you get outside a lab/med facility is actually bullshit and that everything is always racemic all the time. I cannot on that, nor would I really agree wth that statement. However I am also not in any position to claim authority on this matter, so anything is possible unless proven otherwise. Any real Ketamine experts are welcome to chime in and grace the masses.

In conclusio; though 'S' Ketamine is definitely 'more powerful' than its right-handed sister, that is no indication that it is in any way 'better' and that the other is shit. 'R' Ket is friggin dope and a chill time and I would always reccomend it to anybody. Still no matter what always test your ket tho coz they're putting more bullshit like Xylazine and elephant-cock softener and whatnot in street score.

In the uk what do you suppose the average stuff is? K or S? Or something else? Just curious

 

[paranoid android]

S ketamine s so much better then r ket

 

[Mjäll]

I find racemic is optimal. If what i've tried was even S and R, i agree with your experiences insofar as S is more potent and dissociative but lacking some sophistication while R is very mild but also somewhat more conplex feeling. Also R seems to last longer. Anyway i remain skeptical since i have no way of testing for isomer.

 

[Syntherize]

'R' isomer should really be called 'D-Ketamine' to keep up with the Latin but Scientists get dumber and dumber each year so whatever.

There's much debate (online, as far as I can tell) as to what really differentiates these two isomers of Ketamine: Many people believe (including whoever wrote the Wikipedia article) that the 'S-Ketamine' is significantly more potent than the 'R' isomer, which is supposedly a better general anaesthetic. I'll share what I've encountered in my experiences as I have had the privilege of doing *both* at points in time.

The 'S' feels like a retard-iffier drug - but at the same time it definitely is strong as fuck. It characteristically comes in little crystalline shards that must be crushed up (very satisfying) before you ingest. I snort some and consistently lose 50 IQ points and start drooling all over myself. It feels like I'm buzzing throughout my entire body but have a feerish state of mind. Reaching the 'K-hole' is very easy on this one which is not always a positive thing. You totally forget what time is becase you're so retarded you just focus on what your dog-like eyes are oriented towards. If you've never K-holed before, It best represents what Jacob Singer went through in Jacob's Ladder. (horrific dissocociative hallucinatory epxerience before you realise that you died ten years ago in the jungles of Vietnam - and this is the last gasp of your conciousness) Almost as if not more fucked than shroom-induced psychotic episode.

The 'R-Ketamine' is another story: Definitely much weaker so to speak, but I personally beleive is a much more accessable experience. This one looks like a big quartz rock that you have to smash up. I never felt like I was a true retard off this stuff - I could still have fun on this and realistically do things at the same time; what really does it for 'R' though is that all its 'trips' are inside your head. For example, the first time I did it it felt a hypnagogic dream where you swear that you turned off the lamp; or that you got up form the cough to wash your hands, while in reality you've been sitting still for the last ten minutes bobbing back and forth while your head feels like its doing summersaults in the void. You are definitely still smart enough to remember what time is, (or who and where you are) but it feels like it's drawn out tenfold and you'll start wondering if maybe you shouldn't have done this while you're supposed to be writing a paper. This was also my first Ket isomer which my boys were telling me was 'the trippier one' which I would somewhat stand by - but that is definitely a biased impression that I was given beforehand.

Now there's some people out there who also claim that all the 'R' or 'S' you get outside a lab/med facility is actually bullshit and that everything is always racemic all the time. I cannot on that, nor would I really agree wth that statement. However I am also not in any position to claim authority on this matter, so anything is possible unless proven otherwise. Any real Ketamine experts are welcome to chime in and grace the masses.

In conclusio; though 'S' Ketamine is definitely 'more powerful' than its right-handed sister, that is no indication that it is in any way 'better' and that the other is shit. 'R' Ket is friggin dope and a chill time and I would always reccomend it to anybody. Still no matter what always test your ket tho coz they're putting more bullshit like Xylazine and elephant-cock softener and whatnot in street score.

The R/S nomenclature is used in organic chemistry due to the fact that some molecules have multiple positional optical qualities while the D/L is used mainly in biology in order to distinguish active vs inactive compounds. Most all amino acids and other endogenous hormones in the body are of the D variety versus the inactive L variety except for some minor exceptions. I used to think it was all bullshit too once upon a time, but there is good reasoning behind the science, and it wouldn’t be so if it was useless as you say. As for ketamine, I think racemic is best, but yes you can separate some racemic compounds into their respective isomers just as you can do with methamphetamine and MDMA as well among many others.

 

[4DQSAR]

The laevo/dextro nomenclature was dropped because it was based on which direction polarized light would be rotated if shone through a known volumn of a known concentation of the chiral compound in solution.

Syntherize has explained it far better than I could but I thought you might wonder why there was this odd, outdated system that persists. It's because people whose field is adjascent to organic chemistry learn names by rote and renaming an existing medicine itself carries the risk of causing needless confusion.

Clinicians are amazing but they can't be expected to remember the absolute structure of the thousands of medications they prescribe.

So dexamphetamine stays dexamphetamine because as long as the clinician knows what they are presribing after considering the risk/benefit ratio, interactions and so forth, the name just isn't so important.

 

[KetWise]

Hey would you think veterinary ket might be R ket from by product of S separation or it is possible than a synth is dirtier and cheaper than others and feels much heavier and sick/weak feeling it is good for anesthesia and cheaper and animals wont complain?

 

[Syntherize]

Hey would you think veterinary ket might be R ket from by product of S separation or it is possible than a synth is dirtier and cheaper than others and feels much heavier and sick/weak feeling it is good for anesthesia and cheaper and animals wont complain?

It’s the same shit man and probably racemic. You’re all over complicating this…

 

[placebonaut]

It characteristically comes in little crystalline shards that must be crushed up (very satisfying) before you ingest. This one looks like a big quartz rock that you have to smash up.

you can't tell R v S v racemic from how they look, you can get shards, crystals and powders of all the 3 types of ket

(horrific dissocociative hallucinatory epxerience before you realise that you died ten years ago in the jungles of Vietnam - and this is the last gasp of your conciousness) Almost as if not more fucked than shroom-induced psychotic episode.

what?

I would NOT describe ket this way at all, there's nothing horrific or psychotic about it.

A hole is a wonderful and amazing gift, full of learning and insight.

This was also my first Ket isomer which my boys were telling me was 'the trippier one' which I would somewhat stand by

R isn't trippy, it's mild for sure in terms of disassociation, but it has anxiolysis effects

In the uk what do you suppose the average stuff is? K or S? Or something else? Just curious

the vast majority is Racemic (assume it is unless it's been sold explicitly as R or S by the vendor, though the little scoundrels do lie....), that's the most commonly manufactured globally for medical and animal use

It’s the same shit man and probably racemic. You’re all over complicating this…

IIRC all vet use ket is racemic

 

[4DQSAR]

Well, in man clinicians now generally use Esketamine, which is (S) ketamine because it's pretty selective in being an NMDA antagonist. But (R) ketamine is more or less a dopamine modulator. I didn't parkake but the BLer who developed MXE began by resolving ketamine and so had some (R) ketamine which I and several others were invited to sample. When the others reported it was 'A lot like cocaine', I decliced, not being a fan of cocaine.

But you can find the affinity data of raecemic ketamine and seperately, both of it's stereoisomers. I seem to recall Arketamine (if that indeed is what it's known as) and that it has, indeed far more prominent dopamine reuptake activity and far less NMDA activity.

https://www.bjanaesthesia.org/article/S0007-0912(17)38579-3/pdf

I found the above. If you look in the list of references you can explore why the pharmacutical industry is 'retooling' to produce products containing just one stereoisomer.

I appreciate that hearsay and anectoral information has little more to offer than a nudge in one direction but please, go ahead and fill your boots. If your own experiences with (R) ketamine are significantly different. I can only say we were invited to read the instrumental analysis so at least I can be fairly confident what was on offer WAS not just ketamine in which one steroisomer pedominated but that it was the absolute chiral material.

 

[4DQSAR]

BTW I believe resolution was undertaken using L-(+)-tartaric acid and I found a patent for you to peruse:

ES2296757T3 - PROCESS TO ISOLATE THE ENANTIOMERS OF CETAMINE. - Google Patents

A process for obtaining the enantiomers of ketamine which is characterized by comprising the steps that consist of: (a) Preparing a solution of racemic ketamine base in a solvent miscible with water selected from the group consisting of C1-C6 alcohols, tetrahydrofuran and acetone or mixtures...

patents.google.com

Obviously you can equally resolve using R-(-)-tartaric acid if you wish.

I've been told (S)-camphorsulfonic acid is also a viable option. I suppose the advantage of using tartaric acid is you end up with a non-toxic salt, but there are patent that use it. Whichever you choose, the inventors named on the patent are searchable so you can find published academic papers which will almost certainly provide far more detail. As someone noted, 'The goal with ANY patent is to ensure you have legal protection while providing as little information as possible to others seeking to make use of them'.

Now I can't recall which BLer put that truth into words. But it wasn't me. I generally find patents useful in that they tell you something is WORTH patenting but you need to find the associated articles to know the fine detail. I mean, I subconsciously recognized the truth but never thought to make it clear to others.

So whoever it was, if you make yourself known, I WILL attribute the quote to you.

 

[Syntherize]

Well, in man clinicians now generally use Esketamine, which is (S) ketamine because it's pretty selective in being an NMDA antagonist. But (R) ketamine is more or less a dopamine modulator. I didn't parkake but the BLer who developed MXE began by resolving ketamine and so had some (R) ketamine which I and several others were invited to sample. When the others reported it was 'A lot like cocaine', I decliced, not being a fan of cocaine.

But you can find the affinity data of raecemic ketamine and seperately, both of it's stereoisomers. I seem to recall Arketamine (if that indeed is what it's known as) and that it has, indeed far more prominent dopamine reuptake activity and far less NMDA activity.

https://www.bjanaesthesia.org/article/S0007-0912(17)38579-3/pdf

I found the above. If you look in the list of references you can explore why the pharmacutical industry is 'retooling' to produce products containing just one stereoisomer.

I appreciate that hearsay and anectoral information has little more to offer than a nudge in one direction but please, go ahead and fill your boots. If your own experiences with (R) ketamine are significantly different. I can only say we were invited to read the instrumental analysis so at least I can be fairly confident what was on offer WAS not just ketamine in which one steroisomer pedominated but that it was the absolute chiral material.

I loved MXE back when it was still a legal RC in the USA

 

[4DQSAR]

Well, we discussed what was likely to be 'the next step' in terms of arylcyclohexlamine-class NMDA Antagonist/dopamine modulating agents. They make the very reasonable point that the extant literature seems to indicate that swapping the methyl ether to an ethyl ether is very likely to produce something with similar effects. My argument is that there is evidence that the body seems more able to deprotect those larger ethers e.g. ethylmorphine (Dionine™) which based on various writings of opioid users of the 1940s and 1950s was preferred to codeine BUT I freely admit I don't know what enzyme deprotects the ether on MXE.

For my ownpart I have a strong suspicion that what we agreed to term CMXE was developed by Parke Davis seven years after ketamine has several oddities that make me suspect they at the same time wanted to ensure nobody else could patent it BUT not to disclose the details. MXE was based on work from the 1960s which hinted that a meta methoxy gave the scaffold more 'oumph' BUT to be clear, MXE was a novel invention and the patent credits the inventor.

But why would as US company choose only to obtain a BRITISH patent? My hypothesis is that in the pre-internet era, while US pharmacutical companies looked at each others US patents, checking foreign patents would have been next to impossible. Don't forget, at this time to get a copy of a patent you sent off a cheque and 7-14 days later a mimeograph of said patent would arrive at your door. But the logistics of doing that same thing for EVERY nation was impractical... insane in fact as in most cases a technnical translator would have been needed.

Hence:

GB Patent 1202834 'NOVEL CYCLOHEXANONE COMPOUNDS AND PROCESS MEANS FOR THE PRODUCTION THEREOF' by Parke Davis (no name of chemist given)

That covers 2-Amino-2-(2-chloro-5-methoxyphenyl)cyclohexan-1-one - Compound 1

We even discused the likely reason why we still see endless examples of vendors just guessing at what ortho or meta monosubstitution MAY work. None do, but monsubsitution is cheaper. Never mind that the patent suggests CMXE is several times more potent or that Parke Davis paid for a patent to legally protect just ONE compound. Think about it - it's more costly to produce, it seems buyers accept the cheaper rubbish, so why spend any more than is absolutely necessary?

Note that the -Cl overlays that of ketamine and the -OCH3 overlays that of MXE - and that the two substitutions are para in relation to one or the other. So from that we may hypothesize that the receptor domain has two lipophilic clefts, one of which is a hydrogen-bond doner and from which MXE derives it's specific properties as well as a cleft which 'anchors' the aromatic. Of course in the case of MXE that HBD is likely one of the reasons MXE is more active, but in the absence of affinity data, we did agree that the increase potency can only be explained BY increased affinity (or CMXE being a super-agonist, a frightening thought).

Think about it in your head - that ring is fixed from opposite sides so the amine (or more specifically the lone-pair of the nitrogen) is kept facing in a very specific orientation - vital for NMDA activity.

Now obviously the caveat is that while we generally think of ketamine and MXE as NMDA antagonists, the truth is that the reason they are so favoured over extremely selective NMDA antagonists such as MK-801 is because their NMDA activity is 'balanced' by their dopamagenic activity. The fact that the patent doesn't even cover the N-ethyl homologue, a modification known to increase only NMDA activity possibly hinting that the N-ethyl was inferior.

Yes, a few users do seem to prefer esketamine but most seem to prefer the raecemic product because (R)-ketamine is a weak NMDA antagonist but x8 more active as a dopamine modulator (and in fact there is synergy between the two enantiomers in the dopamagenic activity).

So all we can say IS that it's more active. We may not even hypothesize that it's 'better' but only that someone put an inexplicibly large amount of resources into protecting one (very) obscure arylcyclohexylamine.