Misc Abofazole, Russian Nootropic GABAergics

[AlphaOdure]

Any new comments on these? I'm on day 3 of afobazole 60mg/daily, also on 2400mg of gabapentin (interested how they may interact? Any experiences?) & 4mg/buprenorphine, also take 100-200 diphenhydramine for sleep; & sporadically take depakote for past seizures (from past BZD abuse, dependency).

My gabaergic system is fairly fucked , last 10 years have been on varied massive doses of them in the heights of my addiction (at 10mg clonazepam/day after moving off of 400mg etizolam/day, then to 20-35ml 2m2b/day in the end; but in addition to using any & all benzos, also had issues with the barbiturate butalbital & also carisoprodol, 2000mg/day & 14,000mg/day respectively, yes you read that right, shit you not: 40-50 pills daily at that time before IV BZD train wreck)

...had massive seizures & delirious agitated hallucinations, hospitalized 5 times for extended stays (shortest stay 6 days, longest 1 month) in this period.

Anyway, So im interested in some experiences w/positive GABAergics to aid in healing, w/no withdrawal, b/c after 6 months clean my vision, memory, & articulation /critical thinking ability are only now returning to normal levels (afobazole/ is thought to upregulate GABAr too, which is why im trying it first)..

im interested in etifoxine (STRESAM) too if anyone has any experience? Any others safe nootropic GABAergics? In combinations with medications/ drugs? Etc

 

[Shortec Stublue!!]

Only very rarely come across this one before Alpha, seems to be made by Olainfarm who first synthesised Phenibut as Noofen I think!!

 

[Wilson Wilson]

Interesting stuff. Fabomotizole is the name of the actual drug. The mechanism of action is unknown, GABA agonism is just one suggestion. Apparently it is very effective for anxiety but not much English language literature can be found about the stuff.

If it is anything like phenibut though I imagine it is highly effective especially for social anxiety.

However be very very sceptical about any claims made regarding a potential GABAergic having no dependence or withdrawal. If it does indeed have GABAergic properties it probably does also cause dependence and withdrawals. Phenibut withdrawals are certainly no joke.

I'd be interested to hear more of your experiences, but personally I wouldn't use something like this daily when so little is known about its mechanism of action. The Ruskis do make some very interesting pharmas though and the Yanks have previously just slightly altered a Russian drug and sold the "new" version worldwide. For example pregabalin is extremely closely related to phenibut. I'm pretty sure Pfizer made just a single chemical alteration to phenibut to create pregabalin. And yet phenibut is the superior drug.

 

[Jekyl Anhydride]

While touching on the gaba system it also hits 2 major Melatonin receptors. I think the NGF & BDNF contribute to it's neuroprotective effects but how the Sigma agonism ties in is the head scratcher,

It is a MAOi and not knowing just how much of one it is, I'd use caution with things like SSRI antidepressants or other serotonergic meds. Depakote and Gabapentin should be fine though.

Hope to hear how it works out.

 

[Dr. Extract]

I've also developed some interest in etifoxine; partly due to that foxy name and also due to lingering anxiety from past bzd, barb, and phenibut abuse. I've read that it's effects are very mild, but that's the direction that I'm trying to go. I'm a musician and benzos are indubitably good for performing but the memory impairments, general sloppiness, and almost certain addiction potential don't do the music any favors; especially since I'm not terrified of performing anymore, there's just this lingering anxiety that I have to overcome almost every time and some shows are very unforgiving on time and schedule. So if anyone has etifoxine experiences.......

 

[AlphaOdure]

I'm a musician and benzos are indubitably good for performing

I'm a musician too, vocalist & guitarist! & yes using BZDs & other general GABAergics (barbiturates, carbamates, & TAA/2m2b) always were my go to's. So far afobazole seems to have a general calming effect in this regard, definitely noticeable- & DEFINITELY reduces that background anxiety level, only 5 months into getting clean from my severe & horrid BZD abuse last 10+ years (i was IV'ing clonazolam , 7000-8000µg (7-8mg) daily at my worst. Has an active dose range of 75-200 µg) but its not intoxicatingly so. It just literally suppresses typical physical anxiety reactions w/o typical benzo-like effects & overt euphoric disinhibition, only way i can describe it so far. But I'm still only a few days in. (No decrease in effectiveness either, if anything more effective as days go by).

It seems like a GABA-type general antidepressant. Additionally i'm not craving extra dosages of my gabapentin as usual (im really interested to see how afobazole affects me when i stop taking gabapentin: every month i go about a week off before my next Rx refill--afobazole supposedly treats ethanol & benzodiazepine w/d so we'll see).

Additionally, i usually get exceptionally wired from gabapentin first few days after my refill, afobazole seemed to balance this out in a synergistic way. When I'm 4-5 day a into a new script gabapentin usually starts to lose its effectiveness (remember im usually 3 weeks on/ 1 week off w/ gabapentin), so I'm also curious to see if afobazole affects this in any way?

If taken 10-20 minutes after buprenorphine seems i "feel" the bupe a little more, but could be placebo

Sleep
I'm sleeping a few hours less but feeling SO MUCH better in the morning. Aside from feeling well rested, it (ie, last nights afobazole dose) seems to almost ENTIRELY suppress any minor morning withdrawal prior to my morning buprenorphine dose.

While touching on the gaba system it also hits 2 major Melatonin receptors. I think the NGF & BDNF contribute to it's neuroprotective effects but how the Sigma agonism ties in is the head scratcher,

It is a MAOi and not knowing just how much of one it is, I'd use caution with things like SSRI antidepressants or other serotonergic meds. Depakote and Gabapentin should be fine though.

I definitely notice the sleepy headspace effect of Melatonin activity, but i wouldn't call it sedating. Also gives me more energy in between gabapentin dosages. I'm usually suffering from anhedonia & lacking motivation as well when gabapentin loses its effectiveness, afobazole definitely combats this. Perhaps it's partially due to the susoected MAOI effect though too?

& speaking of, I've read numerous reports of afobazole increasing the effects of 5-HT2a ligands (LSD & MDMA in the examples i read); no life threatening reactions, but nearly doubled the intensity.

& yes im very curious on the sigma activity, but also perhaps its suspected action of upregulating GABAr?

Europe & The Russians are so ahead in developing novel, non-benzo GABAergics (etifoxine is next on my list). Mainly i suspect to treat alcoholism... I always wondered (& wished) they came up w/ a MAT subutex type GABAergic here, there's plenty of candidates, ie, partial GABA(a) positive allorestic modulators even! I know there's a few traditional benzos that have this quality, which is preferable in a MAT med, but i don't know of any with super strong binding affinity &/or if that's even applicable to a PAM receptor site that regulates chloride ion channel opening.

 

[AlphaOdure]

Interesting stuff. Fabomotizole is the name of the actual drug.

The manufacturer & most discussion around it all refer to as afobazole, so i call it as such. Why wikipedia calls it by its less used name, I do not know

However be very very sceptical about any claims made regarding a potential GABAergic having no dependence or withdrawal. If it does indeed have GABAergic properties it probably does also cause dependence and withdrawals. Phenibut withdrawals are certainly no joke.

Thanks for the warning.
I've been through phenibut withdrawals (only took it daily for 6-8 months) & for me it was manageable. nothing like benzodiazepine, barbiturate, carbamate, or TAA withdrawal (worst GABAergic w/d, & most prone to delirium tremens- whole spectrum ..intensely, deeply real & disturbing hallucinations, seizures etc IME)

And yet phenibut is the superior drug.

I highly highly disagree, phenibut is crap for me. Pregabalin & gabapentin both blow it outta the water.

& pharmacologically they're pretty different- phenibut is a more of a GABAergic, albeit GABA(b), whereas Pregabalin acts like a traditional gabapentinoid.

Gabapentinoids act at α2δ(-1 & -2) receptors & voltage dependent calcium channels, even though phenibut is technically thrown into this category (this is a chemistry classification tho, not a pharmacological one, b/c of its GABA analogue like molecular structure. not b/c of similar
pharmacodynamics which is what's more relevant to our discussion) it feels nothing like the others. In fact phenibut felt more like the other GABA(b) agonist I've tried, 1,4-butanediol.

Afobazole isn't in either class though, it doesn't seem to bind to or affect chloride openings in ion gated channels as a positive allorestic modulator like benzodiazepines & other typical GABAergics. It may have some straight agonism though (etifoxine seems to for sure, which is next on my list)

I'm more excited about its cumlative GABA upregulating effect & potential positives there.

I added more recent relevant experience info w/ afobazole in my previous post above, however it still may be too soon to tell, its day 5, i think?

 

[AlphaOdure]

Sleep
In addition to vastly improved quality of of sleep (far superior than melatonin); i noticed increased dream activity (or perhaps ability to recall them?)

But no increase in "disturbing dreams" like anticholinergics or nicotinics (bupropion, chantix, nicotine patch). In fact dreams are quite lucid & pleasant.

Also one more side note, a study was done measuring some odd anxiety index I've never heard of (& didn't quite understand) for afobazole vs. phenazepam & the former had favorable effects.

I'll try to find it & post when i have more time, to see if someone else can understand this study's qualitative rating systsm.

 

[AlphaOdure]

Cannabis
GREATLY increased the effect of cannabis, to point i had to lie down. But I quickly returned to very social & happy mindset a mere 10-20 min later.

But, i also had 2 beers, & ethanol usually makes me dysphoric later on (& gives me ataxia easily, ie, dizzy) so it could've been this.

& also mind you this is only the 3rd time I've smoked cannabis since getting clean off of my decade-plus-dependency on GABAergics; so a cannabis experience could be highly subjective.

But, absolutely zero paranoia, where as two previous times i smoked (since getting off GABAergics), i had to actively concentrate on repressing paranoia &/or edginess; even though I had smoked probably only a half or a third of what i smoked here recently while on this afobazole regimen.

DEFINITELY helps with cannabis paranoia in prone/sensitive individuals. Too bad you couldn't use it for tripping b/c of its additive potency effect on serotonergics/ inhibiting MAO enzymes.

 

[Wilson Wilson]

The manufacturer & most discussion around it all refer to as afobazole, so i call it as such. Why wikipedia calls it by its less used name, I do not know

Because that's a brand name, while the name Wiki uses is the name of the drug itself. It's like Xanax is a brand name while alprazolam is the actual drug.

I highly highly disagree, phenibut is crap for me. Pregabalin & gabapentin both blow it outta the water.

It is subjective of course. Depends what you are after. Pregabalin has me utterly mashed all day, I can barely think, have major memory loss, it impairs me far more than any benzo. Phenibut on the other hand provides clearheaded anxiety relief and social confidence. I far prefer that. If I wanted to get high, I'd use pregabalin. If I wanted to go out and have no anxiety I'd use phenibut.

pharmacologically they're pretty different- phenibut is a more of a GABAergic, albeit GABA(b), whereas Pregabalin acts like a traditional gabapentinoid.

They have different mechanisms of action yes. As far as anyone knows so far pregabalin has no GABAergic properties despite its name. It acts primarily as a calcium channel blocker. And yet it has far worse withdrawals than any GABAergic I have used.

But from a chemistry standpoint they are very similar.

Anyway very interesting to read your experiences with this new drug. I am curious myself. But I remain sceptical of a GABAergic that lacks dependency issues. Time will tell.

 

[AlphaOdure]

Because that's a brand name, while the name Wiki uses is the name of the drug itself. It's like Xanax is a brand name while alprazolam is the actual drug.

Lol yea, i know, i know how generics work & the etymology of pharmaceutical brand names. My mix up tho.

But you're right it does seem afobazole is the trade name, which is odd b/c a lot of the research overseas refers it to as such, rather than the chemical name fabomotizole?? So i mixed the two up.

Additionally it seems some papers & researchers use the two terms interchangeably, which is further confusing (I saw afobazole more often so went w/ that)

Its odd that some (Russian, i assume) researchers would do this..? Ie, a study here of, say, etizolam wouldn't be referred to as etilaam? (or whatever Japanese equivalent trade name is used currently)

Oh well

 

[AlphaOdure]

Pregabalin has me utterly mashed all day, I can barely think, have major memory loss, it impairs me far more than any benzo. Phenibut on the other hand provides clearheaded anxiety relief and social confidence. I far prefer that. If I wanted to get high, I'd use pregabalin.

Yea this is what i was trying to convey, its the opposite for me, gabapentinoids are extremely anxiolytic, they do not sedate me at all--in fact they're extremely stimulatory. They completely resolve my social anxiety w/o extreme GABAergic-like intoxication, & also w/o an extreme disinhibiting effect on behavior (ie, doing or saying something you later regret)

Whereas phenibut actually was anxiogenic above certain dosages for me. It was also extremely sedating in an odd way. Didn't consciously feel sedated but slip almost instantly into a phenibut "coma" for a few hours where I'd probably sleep through an earthquake w/o waking up.

Then, I'd emerge from a few hours long phenibut 'coma' extremely agitated, severe tremors & extreme ataxia. On one occasion i couldn't even walk or talk. i was drooling uncontrollably & all my muscles locked up. could not move. Scary. It resolved in -10 minutes & it may have been a type of seizure? The entire experience was also very anxiogenic & may have been a severe panic attack? The EMS guys were baffled too?

Plus phenibut seemed to give me a mentally dulling effect, & a "dumbed down" quality. I don't get this from Gabapentinoids. The opposite actually, almost nootropic, i can definitely articulate better & perform music better.

AND it makes me EXTRNEMLY horny, phenibut lacked this quality too, for me at least?

 

[AlphaOdure]

They have different mechanisms of action yes. As far as anyone knows so far pregabalin has no GABAergic properties despite its name. It acts primarily as a calcium channel blocker. And yet it has far worse withdrawals than any GABAergic I have used.

Well as i mentioned before, saying its a calcium channel blocker is pretty broad & includes a huge number of ligands, from ethanol to magnesium to a shitload of Anticonvulsants.

More accurately they block a kind of ion channel called VDCC, or a voltage-dependent-calcium-channel, or sometimes a VGCC, voltage gated calcium channel (b/c there's other CCB/ ion channel receptor types like ligand calcium channels, NMDAr AMPA others fall into this category although aren't limited to calcium)

At that, we know gabpentinoids are selective at the α2δ1 & α2δ2 (alpha2delta1 & alpha2delta2) subunits. Phenibut lacks this action (as far as i know?), in favor of the GABA(b)r.

especially since GABA(b) is a different type of a receptor, its a G-protein & not iosotropic.

& GABA(b) ligands mostly interact w/ potassium, unlike GABA(a) w/ chloride; & unlike calcium blockers in Ca(2+) ion channels, (Altho there ia some minor overlap w/ the latter, some GABAergic ligands can interact w/ calcium on some g-protein CCB's sites, but not as a voltage dependent CCB, but as a ligand CCB--i don't know the pharmacological implications of blocking Ca channels via these different mechanisms, but I suppose there COULD be some overlap here between "GABA(b)ergics" & Gabapentinoids if im getting my pharmacology right)

& yes while we haven't seen direct GABAergic activity in Gabapentinoids (excluding phenibut if classifying things via chemistry &not pharmacology), they do however seem to have some downstream, or indirect, effect. To me at least.

Or the similarities shared could be in the realm of glutamate inhibition downstream somewhere?

But from a chemistry standpoint they are very similar.

& yea in chemistry phenibut is grouped w/ Gabapentinoids b/c of its analogous molecular structure relative to GABA.

But we were talking pharmacology here (not chemistry or syntheses). phenibut is definitely a GABAergic in that respect.

Similar to how one would group kratom as "opioidergic" despite it lacking any relatable opiate molecular skeleton.

Nor would we classify kratom & its alkaloids as a "yohimbe-like indole" (over an opioidergic classification) just b/c it has an analogous molecular structure to it, when- talking pharmacodynamics at least (again, b/c we're not talking chemistry)

Lol that's all i meant, sorry to geek out on my response, i love talking pharmacology.

But the scientific community would be well served to better articulate these differences & distinguish these classification systems more clearly relative to areas of study!

 

[AlphaOdure]

Update-

• Quality of sleep increased, but w/ very little acute sedation
• Just very clean anxiolysis
• By "clean", i mean that it lacks any other major physiological effects-
  • no major disinhibition
  • no euphoria in traditional sense
  • no memory impact
  • no coordination effects
  • no substantive immediate impact/change in mood.
• Lacks effects on mood most commonly sought after in psychoactives; but general positive mood increase w/ anxiety suppression via seemingly an antidepressant like effect as cumulative, daily use continues (still minor acute effect though)
  • however, i hate SSRIs, & this does NOT feel like one. It definitely feels more grounded in an anti-glutamatergic or GABAergic effect; or possibly the Sigma receptor system? (if we ever find out more about its function)
• I don't think it would be adequate for acute symptoms (panic attacks), geared more to GAD
• DEFINITELY helpful for cannabis/cannbinergic paranoia (acute/single use or cumulative)
• Seems to decrease irritability, anxiety, craving associated w/ very minor opioid w/d (experience limited to only buprenorphine MAT tho)
• Seemed to slightly decrease enjoyability of ethanol (could be subjective tho, b/c i really don't enjoy it in the first place)
• But also decreased negative side effects of ethanol. Haven't really combined enough to give anymore concrete info
• Would be more useful to calm potential anxiety for psychedelics relative to dulling/blunting effect of BZD's.
  • However, DUE TO POTENTIAL MAO INTERACTIONS, it does seem to potentiate 5-HT(2a) agonists (serotonergics).
• In case report of simultaneous LSD & MDMA use (5-HT2a ligands) no life threatening/ extreme adverse reactions were reported (ie, serotonin syndrome); however the user estimated the effect was roughly doubled with 10mg of fabomotizole

(i still use 5-HT2a agonist psychedelics & NMDAr antagonists, so if i happen to combine i will report)

 

[Wilson Wilson]

Yea this is what i was trying to convey, its the opposite for me, gabapentinoids are extremely anxiolytic, they do not sedate me at all--in fact they're extremely stimulatory. They completely resolve my social anxiety w/o extreme GABAergic-like intoxication, & also w/o an extreme disinhibiting effect on behavior (ie, doing or saying something you later regret)

Whereas phenibut actually was anxiogenic above certain dosages for me. It was also extremely sedating in an odd way. Didn't consciously feel sedated but slip almost instantly into a phenibut "coma" for a few hours where I'd probably sleep through an earthquake w/o waking up.

Then, I'd emerge from a few hours long phenibut 'coma' extremely agitated, severe tremors & extreme ataxia. On one occasion i couldn't even walk or talk. i was drooling uncontrollably & all my muscles locked up. could not move. Scary. It resolved in -10 minutes & it may have been a type of seizure? The entire experience was also very anxiogenic & may have been a severe panic attack? The EMS guys were baffled too?

Plus phenibut seemed to give me a mentally dulling effect, & a "dumbed down" quality. I don't get this from Gabapentinoids. The opposite actually, almost nootropic, i can definitely articulate better & perform music better.

AND it makes me EXTRNEMLY horny, phenibut lacked this quality too, for me at least?

It's funny how different people react so differently to the same drugs isn't it?

To me pregabalin provides nothing but extreme intoxication even at low doses while phenibut kills all anxiety, feels stimulating, and leaves me with a clear head.

The effects you got from phenibut sound like what I get off a high dose of pregabalin. I also am extremely prone to losing things on pregabalin.

As for the horn, I get that from both pregabalin and phenibut, but phenibut also increases the actual sensations of sex and I swear it even seems to make me last longer. It is the perfect drug for me to be on when I'm on the pull. Social confidence, no anxiety, high sex drive, and more sensations.

Lol yea, i know, i know how generics work & the etymology of pharmaceutical brand names. My mix up tho.

But you're right it does seem afobazole is the trade name, which is odd b/c a lot of the research overseas refers it to as such, rather than the chemical name fabomotizole?? So i mixed the two up.

Additionally it seems some papers & researchers use the two terms interchangeably, which is further confusing (I saw afobazole more often so went w/ that)

Its odd that some (Russian, i assume) researchers would do this..? Ie, a study here of, say, etizolam wouldn't be referred to as etilaam? (or whatever Japanese equivalent trade name is used currently)

Oh well

Yes that is odd for a trade name to be used in a research paper. Maybe that's just how they do it in Russia? Could also be because the papers are written by the company that developed it as if often the case for relatively novel pharmaceuticals.

 

[Xorkoth]

I've had both etifoxine and afobazole. Honestly I noticed nothing from etifozine even when I took 4 times the recommended dose. I was trying to use it to combat some anxiety I was going through at the time and it felt worthless. I have never taken afobazole more than 2 days in a row, I have basically a whole box and haven't bothered trying, but maybe I will sometime as I hear its benefits slowly develop.

Phenibut is actually a gabapentinoid, but it is also a strong GABA-B agonist so it's got another mechanism of action going on at the same time. @AlphaOdure, have you taken GHB? If so, did you like it? GHB works as a strong GABA-B agonist too (also a GHB receptor agonist) and I find its effect similar to phenibut but much more acutely euphoric and intoxicating, and much, much shorter with a way worse rebound.

As for the horn, I get that from both pregabalin and phenibut, but phenibut also increases the actual sensations of sex and I swear it even seems to make me last longer. It is the perfect drug for me to be on when I'm on the pull. Social confidence, no anxiety, high sex drive, and more sensations.

Absolutely, phenibut is the second best sex enhancing drug for me, second only to GHB which is otherworldly and animalistic and makes me last exactly as long as I want to, oh my god I can't do GHB anymore because I can't control it but sometimes I wish I could magically have a night's worth like once a month and just have those be GHB sex nights. But yeah phenibut is almost as good, it does increase control and definitely sensations.

For me stimulants make me want sex a lot, but performance is greatly affected usually.

 

[Wilson Wilson]

Absolutely, phenibut is the second best sex enhancing drug for me, second only to GHB which is otherworldly and animalistic and makes me last exactly as long as I want to, oh my god I can't do GHB anymore because I can't control it but sometimes I wish I could magically have a night's worth like once a month and just have those be GHB sex nights. But yeah phenibut is almost as good, it does increase control and definitely sensations.

For me stimulants make me want sex a lot, but performance is greatly affected usually.

I have heard phenibut is basically GHB lite. If I ever get a chance to try GHB I certainly will.

And yeah with stims you feel horny but can't really do anything about it. It's annoying when you're all loved up on MDMA with your girl but your cock is shrivelled haha.

 

[Xorkoth]

Yeah I hate stim dick, it's so unfair. It's also hard to pee.

Phenibut is like the methadone of GHB combined with gabapentin. It lasts for over 24 hours and it has a combination of gabapentin's and GHB's euphoria. GHB just has a hell of a peak effect that is one of the best feelings there is but then it rapidly drops off, whereas phenibut slowly builds to a similar but less intense euphoria and then stays there for a long time and slowly trails off. I prefer phenibut honestly, but it's only because of (a) the duration (GHB is too short), and (b) I can control my use of phenibut, whereas GHB grabbed me by the balls with the quickness.

 

[Wilson Wilson]

Yeah I hate stim dick, it's so unfair. It's also hard to pee.

Phenibut is like the methadone of GHB combined with gabapentin. It lasts for over 24 hours and it has a combination of gabapentin's and GHB's euphoria. GHB just has a hell of a peak effect that is one of the best feelings there is but then it rapidly drops off, whereas phenibut slowly builds to a similar but less intense euphoria and then stays there for a long time and slowly trails off. I prefer phenibut honestly, but it's only because of (a) the duration (GHB is too short), and (b) I can control my use of phenibut, whereas GHB grabbed me by the balls with the quickness.

Thanks for the comparison. Phenibut does sound like the better drug of the two. I can understand why GHB is considered so addictive when it has an intense euphoria but only a short duration. Would still like to give it a go at some point though.

 

[AlphaOdure]

Phenibut is actually a gabapentinoid, but it is also a strong GABA-B agonist so it's got another mechanism of action going on at the same time.

Right. Phenibut is a Gabapentinoid from a chemistry standpoint.

But, for example..
We usually refer to kratom (& it's alkaloids) as opioidergic due to its behavioral effects & pharmacology, even tho its molecular structure from a chemistry standpoint is that of an indole (which groups it w/ yohimbe/ yohimbine, tryptamines, & a whole host of pharmacologically unrelated chemicals)

...so, I was just saying its more relevant to speak of phenibut in the same way: as a GABAergic separate from Gabapentinoids in our context of discussing behavioral effects/phatmacology.

Since we're not really talking chemistry... See what i meant?

B/c in pharmacology phenibut lacks traditional gabapentinoid action at the VDCC (calcium channels) subunits α2δ1 & α2δ2 (alpha2delta1 & alpha2delta2) which is mostly responsible (we think) for all effects shared by pregabalon, gabapentin, & others being developed & researched.

(Altho they all probably share some downstream common effect?).

& as you know, phenibut acts on GABA(b) while all 'traditional' gabapentinoids do not. making phenibut more of a GABAergic in this context..

That was my only Point lol