PCP analogs (Cumulative) - Retrospective - Bioassays

[Jamshyd]

Like I said in almost all discussions concerning K analogues, I personally do not see the point in increasing the analgesic effects.

Methoxetamine is interesting, but I still find it inferior to K in all respects except hedonism.

I guess I'll have to repeat once more, that to me anaesthesia (no-sensing) is a very, very, very different thing from analgesia (no-hurting). The former is seen in Nitrous Oxide, the latter in Aspirin and Morphine. I think we can agree that these two things are very different.

(I think I need to save my anaesthesia/analgesia shtick and use it for c/p since it seems no one takes note of it no matter how many times I repeat myself )

Interestingly, Methoxetamine is FAR more analgesic than K, yet is completely devoid of anaesthesia.

With that said, I think that anaesthesia - sensory deprivation - is a very important part of the shamanistic aspect of Ketamine's entheogenic effects. Ketamine is unique in that it produces such strong anesthesia while preserving consciousness. People who are trying to make a more psychedelic-like Ketamine have the wrong idea as far as I'm concerned. If you want quality psychedelics, go play with ergolines . Mind you, anaesthesia is not the only good thing about Ketamine. IME, Nitrous Oxide is a stronger anaesthetic than K, yet it lacks much of the latter's usefulness.

I personally do not care about making money. I don't mind it if a quality ketamine analogue happens to be less potent. My concern is bringing to attention the medicinal qualities of Ketamine or a superior analogue should one be found.

What I personally look for in a K analogue - one which preserves the anaesthetic qualities of K - is the following (in order of importance):

1. Less renal toxicity.
2. Slightly longer duration.
3. Less habit-forming
4. More pronounced/enhanced overall effects.
5. (Theoretically) - a medicine that retains all of K's qualities but circumvents its stigma to allow further research into its miraculous therapeutic effects.

From your description, it seems that N-ethylnorket comes very close to fulfilling some of the above (2, 4, 5), and (1) particularly if we were to accept the theory that renal toxicity is due to norketamine (unconfirmed, afaik) and that the N-Ethyl homologue circumvents this metabolic step. If anything, this compound will help prove or disprove the theory surrounding renal toxicity.

As you may have guessed for now, I actually think K is wonderful as-is. It is the little details that I think can be improved to create a better sacrament and medicine - euro vendors be damned .

 

[crOOk]

Uhm, this is pcp thread dude. In case you're going to combine those tryptamines with PCP, I've only had disappointing experiences that way. Ketamine+tryptamine=win though (especially DPT). DMT and PCP was the most disappointing combo I've ever tried...

 

[crOOk]

What I personally look for in a K analogue - one which preserves the anaesthetic qualities of K - is the following (in order of importance):

1. Less renal toxicity.
2. Slightly longer duration.
3. Less habit-forming
4. More pronounced/enhanced overall effects.
5. (Theoretically) - a medicine that retains all of K's qualities but circumvents its stigma to allow further research into its miraculous therapeutic effects.

As you may have guessed for now, I actually think K is wonderful as-is. It is the little details that I think can be improved to create a better sacrament and medicine - euro vendors be damned .

A lower dosage and higher oral/intranasal/rectal bioavailability would be desirable, most of all lack of undesired metabolites with those routes of administration. K is wonderful IM, but insufflated or even oral it's far less impressive.

 

[Jamshyd]

^ I agree.

But I was referring to adder's talk about making more money. Obviously, potency is most important to those who produce and sell drugs. It is only convenient to those who simply use it, but not necessary by any means.

I personally wish something identical to Ketamine is discovered that is active in the single-digits for the sole purpose of it being easier to turn into a time-release patch. Such a device would be fantastic for its use as anti-depressant.

My finding is that 10 - 15mg (NOT MORE) of K IMed every 30 - 45 mins for 3 - 5 days produces anti-depressant effects that last at least 3 weeks after the final dose. This has been consistent over 6 years of trial and error. If an analogue is found with an identical effects profile that is 10X as potent, it can become reasonably easy to create a patch that releases 100 - 150mics over a 24hr period and should have a similar efficacy to IM.

 

[crOOk]

^ I agree.

But I was referring to adder's talk about making more money. Obviously, potency is most important to those who produce and sell drugs. It is only convenient to those who simply use it, but not necessary by any means.

I personally wish something identical to Ketamine is discovered that is active in the single-digits for the sole purpose of it being easier to turn into a time-release patch. Such a device would be fantastic for its use as anti-depressant.

My finding is that 10 - 15mg (NOT MORE) of K IMed every 30 - 45 mins for 3 - 5 days produces anti-depressant effects that last at least 3 weeks after the final dose. This has been consistent over 6 years of trial and error. If an analogue is found with an identical effects profile that is 10X as potent, it can become reasonably easy to create a patch that releases 100 - 150mics over a 24hr period and should have a similar efficacy to IM.

You are aware of the pharmaceutical industry's plans to develope antidepressants which utilize (selective) NMDA antagonism as their main mechanism of action right?
Personally, I don't know how an antidepressant could feel more natural then those after effects you described. I experienced the very same thing with DXM and PCP. While it is very irreliable with DXM and Ketamine, PCP has always been 100% reliable. The antidepressant effects last about 10-20 days for me.
If you're interested in those selective antagonists, there are running clinical trials and I've posted a thread about it on bluelight... I could point you to a few publications if I can find em. My guess is you just wanna get high though, so fuck selective antagonists without "undesired side effects". ;P

 

[skillet]

What dose of PCP do you use for that crOOk? And is that just from one dose or do you take it for a few days like Jamshyd?

 

[crOOk]

I don't do that anymore. First time was 10mg intranasal, total overkill, but the "afterglow" (~2wks) was absolutely amazing. Later started smoking the stuff which I enjoyed a lot more, started around 5mg and upped to around 30. By the time I got to such a dosage I had started eyeballing the doses and it had also turnt into a daily regimen. :D I wouldn't recommend this to anyone, but I had the time of my life.

 

[skillet]

Oh ok, I thought you might have done it with a threshold or lower dose and was wondering what that would be! I might try with 1-2mg or so for a few days like Jamshyd with ketamine.

I tried it at 2.5mg then 5mg rectally, will have to try a higher dose sometime though I didn't enjoy the 5mg dose. Felt a bit like coming down with flu, but nothing happened the day after (except being a bit tired) and there was no afterglow.

 

[fastandbulbous]

If you're looking for antidepressant effects, then methoxetamine is the best IMO. Single 20mg dose leads to a couple of weeks of improved mood (at present I'm using it sparingly to treat my SAD and it's working better than the best prescribable antidepressants, lofepramine).

The non keto version, 3-MeOPCE also works as a gppd antidepressant

 

[crOOk]

I haven't kept book on my dosing schedule, but I remember larger doses were more likely to cause the antidepressant effects while PCP was the most reliable with the "afterglow" becoming mroe pronounces with increasing dosages.
That being said, it was never a sure thing for me, but when it worked it felt amazingly natural (which isn't saying it was subtle).

The biggest problem about these experiments for me were the habit forming effects these substances caused for me. There's nothing that's ever quite drawn in as much as NMDA antagonists have. That's why selective NMDA antagonists like cp101,606 are being developed. This one is developed by Pfizer.

In addition, Hamilton Depression Rating Scale response was 60% for the CP-101,606Y treated group versus 20% for placebo group. Interestingly, 78% of CP-101,606Y treated responders maintained response status for at least 1 week after the infusion.

Take this with a grain of salt, the substance is also known to have some sigma-1 affinity as well...

EDIT: http://www.bluelight.ru/vb/showthread.php?t=520210&highlight=nmda+antidepressant

 

[leiphos]

Uhm, this is pcp thread dude. In case you're going to combine those tryptamines with PCP, I've only had disappointing experiences that way. Ketamine+tryptamine=win though (especially DPT). DMT and PCP was the most disappointing combo I've ever tried...

yes I meant 4-meo-pcp with 4-aco-dmt

how/why was it disappointing out of curiosity?

 

[crOOk]

I pretty much just blacked out into a vast black nothingness. There wasn't any dmt rush or vivid imagery. While I sure didn't feel at home where the combo took me, I wasn't where either one would usually take me and it wasn't nearly as exciting as either place would be.
It cancelled each other out one some level, but was still quite incapacitating as you'd imagine this very combination to be.

Closer to 5-MeO-DMT (but dark lol), I never liked that stuff either.

I wouldn't say it was a mistake to smoke it along with one another though, there weren't any major side effects, it just doesn't feel like a good mix.

EDIT: I'm sure I've mentioned this at least 20 times before, but it can't be stressed enough. If you're aiming for being absolutely blown away, DPT+Ketamine always did that trick for me. It was DMT+Ket that pretty much turnt me off psychedelics altogether. I still like them and all, but my usage frequeny has dropped to considerably less than once per year and I never feel like I'm seeking any profound knowledge from them anymore. In other words: DMT+Ket are well worth it as well.

 

[Jamshyd]

Crook: I had different results; I found PCP too unreliable, loopy, and produced a "poisoned" feeling for several days.

I am actually not really interested in "just getting high." I use Ketamine at high doses occasionally for purely spiritual purposes. But the ULD self-treatment does not cause much more than a "background" stimulation. It feels very much like gabapentin of all drugs.

Also, I really, really, REALLY doubt that it is simply a matter of NMDA-antagonism. Of all the ones I tried, none worked like Ketamine. Some were more readily euphoric (in the getting-high sense), such as Methoxetamine. But none produced the effect I am after. If I were looking for simple euphoria, I'd use methoxetamine. But that's not what I'm after.

If you're looking for antidepressant effects, then methoxetamine is the best IMO. Single 20mg dose leads to a couple of weeks of improved mood (at present I'm using it sparingly to treat my SAD and it's working better than the best prescribable antidepressants, lofepramine).

The non keto version, 3-MeOPCE also works as a gppd antidepressant

I'd be wary of conflating hypomania with antidepressant effect, but I still wouldn't completely doubt you just yet as you are far more experienced in these than I am.

But I emphasize once more, that the effect of Ketamine is a very specific one that actually seems to be caused by an internal "learning" (or reprogramming) that happens through a minimum of 3 days - any less and you're either content with a ketamine afterglow, or feeling icky from norketamine muddiness (or whatever it is that causes the muddiness).

You'd be surprised at just how different the process is from what you're used to with K. Instead of a tip-of-the-tongue syndrome, linguistic skills are sharpened; one becomes more eloquent and memory becomes vivid and seamlessly accessible. This all sounds like the total opposite of the state of semi-demential that Ketamine abuse leads to - and it is!

It simply isn't a process of take-drug-feel-good. Nor is it an afterglow from a beautiful experience.

I will eventually get to write down my regimen and hope you try it one day and tell me what you think . The trick is to resist the temptation to get high and stick with ULD...

Sorry if I blab too much about this, but I feel there is something very special here that is being missed and trampled over - from here by bladder warnings and a guy telling me I have holes in my head, and from there by the cascade of PCP-analogues that do amazing things but don't really bring to light any of the above . I hope one day someone will see what I see.

 

[adder]

(I think I need to save my anaesthesia/analgesia shtick and use it for c/p since it seems no one takes note of it no matter how many times I repeat myself

No, why? I get it, it's obvious anesthesia is a different thing from analgesia. Anyway, putting someone into an anesthetic state generally also means he/she doesn't feel pain either (without that no surgery would actually be "humane" nowadays). I totally agree ketamine is more worthy than methoxetamine in series of arylcyclohexylamines. Anyway - de gustibus non est disputandum.

I brought up my concern about some RC shops making money off ketamine analog with trifluoromethyl group in place of chlorine (no matter how it works - for some people it simply must be good because -CF3 on phenethylamines means success and it doesn't have to prove right here).

I myself see more potential in ketamine than just a good drug for putting people into anesthesia. But I don't think ketamine would prove to be superior to N-ethylnorketamine or 2-(2-methoxyphenyl)-2-(methylamino)cyclohexanone. Actually, they may only differ in potency and not much in selectivity at different targets.

If you seek for some analog that would last longer and you don't care about its analgesic effects - getting rid of 2-oxo group is the way to go. There's a lot of 2-oxo and 4-oxo compounds that prove a carbonyl group on these positions give analgesics. Some may want to look at US patent 4460604 to see what I'm talking about (it's actually about 4-amino-4-arylcyclohexanones). But at the same time removal of carbonyl group at position 2 (by removal I mean synthesis of compound without it, not working with ketamine and removing it literally) would give a chemical that's harder to metabolize. So I guess, we need some compromise here and that carbonyl group is better occupying position 2 than position 4. 1-(2-chlorophenyl)-N-methylcyclohexanamine would much probably be quite a dirty compound like PCM, just less potent and with some more analgesic properties anyway (for analgesia 4-oxo is better than 2-oxo, 4-oxo-PCP has actually no PCP-like activity but instead it's an analgesic close to morphine in power), I guess that's what chlorine does there, 2-oxo is to ease metabolism, it may add very little to analgesia contrary to chlorine.

Then, changing methyl substinuent on nitrogen to ethyl is another step - it's been proven ethyl is the spot, methyl is worse, anything longer than ethyl starting with propyl is worse (in case of potency). Ketamine has potency already reduced so I'd have N-ethylnorketamine and work on this. Maybe 2-(ethylamino)-2-[2-(trifluoromethyl)phenyl]cyclohexanone is the compound you're looking for. But is really that chlorine at orto position of phenyl in ketamine in any way metabolized?

Well, looking at ketamine's neuropharmacology this special properties you find in it come from one of following actions or combination of some: NMDA antagonism, μ-opioid receptor agonism, σ receptor agonism, D2 partial agonism, DAT blocking. Yeah, this purely scientific approach helps in no way to understand why ketamine is such a great drug for recreation for some people (well, some might say they don't use ketamine as a recreational drug but for some more worthy purposes, I don't care, using is using for me and subjective effects and emotions are different thing).

If you're looking for antidepressant effects, then methoxetamine is the best IMO. Single 20mg dose leads to a couple of weeks of improved mood (at present I'm using it sparingly to treat my SAD and it's working better than the best prescribable antidepressants, lofepramine).

The non keto version, 3-MeOPCE also works as a gppd antidepressant

Right, I guess analgesic part of ketamine activity has something to do with its antidepressant potency. So I wouldn't really want something like "a chemical working exactly like ketamine but with none of its analgesic properties", actually that's impossible as blocking NMDA channel brings some analgesia anyway by itself. Just from a simple comparison between 2 dissociatives completely different chemically - ketamine and dextromethorphan - one can see ketamine's actions at μ-opioid receptor, D2 receptor, and DAT is what makes ketamine different from DXM. I haven't heard of something like "D-Hole". And if I wanted to subjectively compare a state described as "K-Hole" and "4. plateau" - the latter leaves a very dirty feeling to it.

Sorry if I blab too much about this, but I feel there is something very special here that is being missed and trampled over - from here by bladder warnings and a guy telling me I have holes in my head, and from there by the cascade of PCP-analogues that do amazing things but don't really bring to light any of the above . I hope one day someone will see what I see.

"Blab" as much as you want. I know what you want to say by all of this (not being a regular user of ketamine as you seem to be)

Once again, one can get a chemical with properties almost identical to ketamine by playing with ketamine structure in a few different ways. This proves for ketamine to be no "the one and only holy grail". In short that's a reference to what you see in ketamine and what he'd want from some analog of it. Well, if I had been given a work more like "1-phenylcyclohexanamine and propeteries of its analogs", there'd have been a lot more on variety of substitutions on phenyl ring with 2-carbonyl present. Also, what I posted is just a sketch that was used for writing something that some doctor at university could read (trust me, they don't want to read things like "XXVII structure, analog of ketamine, seems to open the third eye much easier than ketamine". All I know aside from the first post, I keep adding when something is brought up and a bulb lights in my head.

From my experiences not really connected with this work, N-ethylnorketamine is stronger than ketamine but that's only dosage. You don't really get something with PCP's duration of action and magic of ketamine in one.

 

[Jamshyd]

^ Wow, nothing short of fascinating. Thank you so much sir, this was a most pleasurable post to read.

Yeah, between a longer duration and preserving the integrity of the entirety of Ketamine's effects profile, I'd definitely go for the latter.

With that said, it really does seem like N-ethylnorketamine (and its 2'-MeO counterpart) is a most promising candidate for a panacea.

Do you have any insight as to whether that compound undergoes a metabolic process analogous to that which gives rise to norketamine from Ketamine?

 

[crOOk]

^ Wow, nothing short of fascinating. Thank you so much sir, this was a most pleasurable post to read.

Indeed.

 

[adder]

Do you have any insight as to whether that compound undergoes a metabolic process analogous to that which gives rise to norketamine from Ketamine?

I've got no linking to any article confirming this but I'm sure N-ethylnorketamine undergoes N-dealkylation. It's still a short alkyl chain for body to do nothing else on it.

 

[Jamshyd]

Interesting.

Have you tried the pyrrolidine analogues, then? I assume - though I could very well be wrong - that SARs-wise pyrrolidine is the closest thing to ethyl that doesn't undergo N-dealkylation (?).

 

[adder]

If you mean PCPy analog with 2-carbonyl on cyclohexyl ring and o-chloro on phenyl (i.e. 2-(2-chlorophenyl)-2-(pyrrolidin-1-yl)cyclohexanone), then no, I haven't taken it. Anyway, from such a compound there would be no way for norketamine to show up as a major metabolite. It's more probable the pyrrolidine ring is oxidized.

 

[Jamshyd]

That is indeed the compound I am referring to .

I'd definitely be interested in seeing it made and tested against N-Ethylnorketamine and Ketamine for Renal toxicity, as such an experiment would probably make or break the assumption that said toxicity is caused by norketamine.