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Which arylcyclohexylamine has the most promising antidepressant effect?

Transcendence

Transcendence

Bluelighter
Joined
Jul 19, 2006
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I have treatment resistant depression and tried every available psychiatric option until only ECT or ketamine infusion were left. I've been receiving medically approved ketamine infusions on a regular basis from the best clinic in the U.S. It is expensive but effective.

I have deep suspicions that other related dissociatives may have a more pronounced ability to fight depression without the necessity of I.V. administration. Something that can be employed transdermally, sublingually, or as a nasal spray.

In my experience, 2F-ketamine is extrememely similar to ketamine. I would estimate about 10-20% less potent, with less pronounced psychedelia but a warmer afterglow and less residual mania. Downside is potency makes it nearly as inaccessible and impractical as prescription ketamine and probably as likely to induce bladder damage.

MXE was potent enough that nasal, oral, and sublingual use was very practical and interestingly led to very different experiences. It had an immediate antidepressant effect at least on par with 2F but unfortunately also more mania and very hard not to fall into recreational overuse and eventual psychosis. I am frankely amazed that nobody is taking advantage of the marketing monopoly considering U.S. legality and it would be a shame to lose this medicine forever.

MXM at 100mg was only practical orally and produced a short but indescribably wonderful psychedelic dissociative experience. It is the most psychedelic and mentally positive disso I've tried. If I could have an infinite supply of any recreational compound on earth it would be this short-lived and obscure jewel. Incredibly therapeutic and the ability to control visual and tactile hallucinations by thought alone. Short acting so that it could be used at night and not carry over into the next day. Although I mourne the unavailability of MXE, at least MXE was well explored and will always be remembered. MXM was only available for a couple months and I never hear it discussed. The most therapeutic and pleasurable and fascinating drug, I would rather mdma be lost to history than MXM. Oh well.

Everything else I've tried (oxo-pcm, oxo-pce, deschloro, 3meopcp, mxp, diphenidine, etc) has not been promising. The first three were bland/soulless mentally while being physically disabling for far too long. The likes of the latter three were too dark, unpredictable, and most of all psychotic to be used regularly.

Is there a arylhexamine I missed that approaches the medical potential of ketamine, 2F-ket, MXE or MXM?
 
It's worth realizing that the AD potential is considered to come from hydroxylated metabolites of ketamine and that AD potential should not be confused with acute euphoria, although that is not entirely what you seem to be doing (3-MeO-PCP for example can be euphoric and manic or hypomanic but doesn't seem likely to produce AD metabolites because it isn't really all that analogous to K - a prime example of where one might be fooled into thinking it is an AD effect).

2'-Oxo-PCM (which IS deschloro by the way) and 2'-Oxo-PCE might be analogous enough but who knows really? I think it is very plausible that 2F is so analogous that it has a similarly active hydroxylated metabolite but not even that is certain. I wanna say that with MXE the potential extends beyond initial euphoria and that I agree that some compounds you mention at the end are 'dark', unpredictable (and some too long-lasting by the way) which could eclipse beneficial effects anyway. Some AD potential seems to be rooted in neuroplasticity effects and maybe this is enhanced by transient dissociative effects disabling rumination loops etc at some level, but then getting on with your life to reap the benefits.
All dissociatives can do this last part to some extent and it can be therapeutic on it's own to 'break the cycle', but it really isn't the primary AD effect we are talking about here (the incredible ones associated with ketamine trials).

Ketamine can do it's job even at low doses, so it's AD potential is not dependent on noticeably strong dissociative 'trip' effects, though I don't know about psychological suspension on a more subtle level at those dosages.

The blandness and soullessness of some disso substances might be a result of lacking monoaminergic effects, leaving you with little besides cognitive impairment and amnesia. Especially when that effect is powerful it just seems way too stalling to be therapeutic.

I can't off the top of my head think of something you haven't mentioned that is all too relevant but my point is that the medical potential of all these analogues is so tentative in the first place that it seems premature to count your chickens.
Take sub-recreational doses of said drugs on their own with a certain regularity and preferably a reliable ROA like IM to assess the potential over a certain period, and don't take anything else. Otherwise it can get so confusing easily that you are just guessing too much. And that is not even double blind or blind ^ .

At such low dosages those nasty effects of O-PCM and O-PCE should not be there, so if they don't obscure any action on mTor pathways you can really assess it better than based on the supposed recreational effects. To guess what those dosages would be like you could try comparing the dose-response curve to K, but since the mTor efficacy is not necessarily that related it might require dosages of O-PCM and O-PCE that come closer to those of ketamine's AD-therapeutic dosages. Which for O-PCM and O-PCE could be pretty 'hallucinogenically' active including nasty effects, making it relatively hard to use in the same way.

I kind of wonder why they don't use the enantiomerically pure hydroxylated ketamine metabolites for AD therapy but I guess it's not really necessary. For research and understanding though, it would be good if they explore analogues of that metabolite to really get to the bottom of that pharmacology and SAR rather than keeping it a peculiar novel effect of ketamine as pro-drug. But I think they are not sitting still on that front. :)

What you are talking about though is hoping to get a lucky shot with an indirect strategy of doing the same, to use analogous pro-drugs and plain hope that you get metabolites with equal or better potential.
 
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No mention of 3-MeO-PCE yet. I suspect this one could work with some people.

Also, I have a hunch there might be something interesting with mixing 3-MeO-PCE and O-PCE. But I've yet to test.
 
Yeah I have high hopes for MXE. Someone should alert researchers of the hydroxylated K metabolites to look into hydroxylated MXE analogues. It seems hard to predict whether 3-MeO-PCE or O-PCE would have such potential. 3-MeO-PCE was extremely Zen but also manic (more than 3-MeO-PCP) depending on dosage, set and setting which makes it more difficult to say something about therapeutic effects, I don't really think they were persisting.
A combination of O-PCE and 3-MeO-PCE is not like MXE per se just because MXE is like the hybrid of those molecules. It would be more like a shotgun approach hoping to get a better chance of something that sticks since we don't know the SAR involved and which groups are critical to the mTor action.

My best guess is that proper groups at the 2 or 3 position are important. The 2'-oxo seems critical for hyperpolarization channels which together with NMDA effects apparently are responsible for the immobilizing anaesthetic effect of arylcyclohexylamines that have the 2-O.

I am curious about the desoxy analogue of ketamine now.. (desoxo? deoxo?)
 
I don't understand the love for the 3-meos, everyone I've seen sample it became incredibly manic and swore not to try it again. Even I had issues with it despite knowing what it was going in. All these people love K and MXE. I wouldn't advise attempting to self medicate with the 3-meos at all.
 
Not sure if you read any of my previous posts but
- one shouldn't confuse recreational effects with therapeutic AD effects
- AD dosages should be much lower (if not the usefulness of the substance is probably doubtful?)

So: even if what one would call recreational effects were not to your liking, or even ones considered side-effects (arguably mania or hypomania are primary effects but again this depends on whether you appreciate hypomania and whether the mania is 'hypo-' or not)...: you shouldn't really notice them much if you would actually take the substances medicinally.

In reality, many people use or abuse these substances recreationally, might hope for AD effects as a bonus but even as an AD alone this may be counterproductive after a while and irresponsible. I'm pretty sure they have a tendency to wanna justify their use or abuse but for the above mentioned reasons that should be considered self-delusion since proper self-medication would involve sub-recreational dosages.

I tried using 3-MeO-PCP medicinally a while ago - the dosages were small in absolute terms and also too low to trip but I did notice effects and was dissociated from it (also stimulated a bit). In retrospect this was misguided: the therapeutic effect was actually me trying to numb and cope during a difficult time and I wasn't depressed as much as I was sad and anxious about personal matters - a healthy response in a way. I also believe 3-MeO-PCP to be an unlikely AD candidate for SAR reasons now. If I really wanted to try it medicinally though, I should probably have done 'trials' in the microgram range.

If you actually separate AD effects from psychotherapeutic effects of trip-dosages and recreational effects, it should hardly matter whether the substance feels nice or not as a recreational drug because from AD perspective you are basically taking an overdose. There is plenty of AD meds that I wouldn't want to overdose on ;)
 
I understand, I'm just saying out of all the compounds begin considered for this I've noticed more bad reactions with 3-meo-pce/pcp than all of the others. The 3-meos just don't seem _that_ fun. I did not take a very large dose and found myself tumbling into a manic state at the end. I've also seen the same thing happen with three other people, one of which took less than I did. All were experienced in the use of various dissos. If you're going to explore them for this purpose proceed with caution. No doubt in my mind they wouldn't be as popular/common as they are right now if the supply of MXE hadn't dried up like it did.
 
I just came here to say the period of my life in which I abused MXE was probably the happiest, most driven, hopeful period I've ever had. It felt like I was on the cusp of something great. Now it's gone and I can't justify wasting my last few grams, so it's back to monotony and self-doubt again I guess.
 
Cream Gravy? said:
I just came here to say the period of my life in which I abused MXE was probably the happiest, most driven, hopeful period I've ever had. It felt like I was on the cusp of something great. Now it's gone and I can't justify wasting my last few grams, so it's back to monotony and self-doubt again I guess.
Click to expand...

I really miss MXE too, I had a lot of fun with it when it was common. I kick myself for wasting the last of it I had watching a 3D movie, if I'd known it'd be impossible to get I would have saved it for a special day. At one point I did consume it too often and became a bit manic but it wasn't anything like the instant mania of the tail end of 3-meo. You really had to abuse the stuff to get to that point with it.
 
Gonna hop on the MXE train too. Something about that chemical just made everything seem okay. In my head and in my body. Like going from "i hate everything I need to die" to "Hey, this isn't so bad. What's up shitty job and dumb people, I love you".

Ketamine would be next for me probably. Doesn't last long enough, too high of a dose, bad body effects nonwithstanding.

3 meo pcp/3 meo pce/ 2 oxo pce would tie for next. I would wake up sometimes without enough sleep feeling bad, take a 1-3mg bump of 3 meo pcp, and have energy and whatnot for work. Just took a large amount of o pce the other day, halfway through the evening I was like "Ohhhh there it is. I don't want to kill myself anymore". It's like some weird weight is lifted from me and I can look at the world differently.

Dck after that. It makes me feel okay, but fucks me up mentally and I can't really go about doing normal shit.

Ephinedine is pretty cool, but I only went through a gram and it has a high dose so I dunno.
 
Yeah, MXE is really special, the mind state it produces is one of the most wonderful and balanced ones I've ever experienced, it is truly magical. Ketamine can't even touch it, nor can any other disso I've tried. The way ketamine works for depression is through its metabolites though, not sure if MXE has the same sort of effect or if it's just a great antidepressant during its primary effects. If that's the case, then it's not sustainable to take any dissociative daily, so it would only be good for the short-term or as something to interrupt depression temporarily during a particularly bad day.
 
I'm yet another who would say MXE is far and away the best for antidepressant use. None of the others (o-pcm/pce, 3-meo's, etc) come remotely close. MXE is the holy grail.. I wait hoping for its return, with the realistic expectation it likely won't. At least I got to throw a ton of it down my gullet while it existed.
 
MXE's antidepressant affect, plus its astral traveling abilities (Who used this frequently and didn't at least once feel like they ended up *somewhere* people were pissed off they discovered?) Tinfoil hat and shit but the fucking UN banned it. TPTB really dont want us having this beautifil chemical.
 
I think 3-MEO-PCE is an antidepressant. Is this working for anyone else like that? I am asking for special reasons...
 
3-MeO-PCP A Antidepressant? (depends)

As a single use/long acting antidepressant....it has been on occasion for some. As a daily use antidepressant....it could be if you are careful...fire is still fire. I suggest look elsewhere.
 
Morninggloryseed, did you answered to my question? I am unsure because you wrote 3-MeO-PCP and I meant 3-MeO-PCE...
 
3-MeO-PCE has one hell of a tasty mania but I don't think that really counts as 'antidepressant effect.' MXE was functionally antidepressant for me. That shit changed my life, even with it unavailable since the ban I have not had the kind or severity of depression and anxiety I used to suffer.
 
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