Is flouro-phenibut probably as safe as normal phenibut?

[deruyityn]

I have sometimes wondered was Mr shulgin just extremely lucky not to have ingested something lethal in all his testing of different compounds? He did live to a ripe old age but is that more of a fluke akin to smokers who live to their 80s who swear by their 20-40 cigarettes a day?

It does seem though that he didn't live an excessive life and would only take modest doses from what I gather but isn't it really lucky that he didn't ingest something that would have caused him permanent damage from one dose?

 

[Weltmeister]

Shulgin started taking the substances at very low doses like 1mcg or less and if it didnt do anything he doubled the dose the day after. This way his risk of having a fatal overdose was actually pretty small. It doesnt reduce the risk of doing unnoticable damage to oneself tho. Shulgin had to get a heart transplant which might have been related to his use of 5ht2b agonists

 

[Limpet_Chicken]

He was most cautious in his approach. Of course it won't protect from everything under the sun, but to cause acutely fatal poisoning a compound would have to be extremely poisonous indeed, at 1ug something would have to be manyfold more acutely toxic in terms of LD:50 than soman or VX nerve agents.

Weltmeister-is it known what his heart complaint was, specifically? as you might be right there. Although that said don't 5HT2b agonists require regular or constant use to cause issues? He DID take quite a lot of serotonergic psychedelics and MDxx however.

 

[serotonin2A]

Shulgin was taking a minor risk but he was always careful to work from structural starting points that were known to be safe. He was mostly testing close structural analogs of known compounds, Additionally, he slowly made his way up to active doses and he never pushed the dose higher thsn was necessary to define the nature of the responsw to a compound.

 

[WSH]

Here is an interview where he explains his dosing strategy (starts at 4min):

Shulgins I have known and loved

I love how the interviewer wanted to start at 1mg and Shulgin laughed his ass off!

 

[deruyityn]

Ye I get that but that doesn't speak of the medium/long term harm the good Doctor may have been doing. But having said that, since he tried so many compounds in his life and lived a long and full life can we not surmise that it is a pretty safe bet that related compounds are going to share the same toxicity profile of their relatives. Aren't the 'essential characteristics' you can determine of basic organic materials? I know you can't say at first but once the initial tests are out of the way in terms of active dosages being established. Bringing it back to the compound at hand the dosage range is known but how can we make predictions of medium term toxicity?

Ie buying a bit and testing it a couple of times a week and then getting regular checkups at the doctors. Will that probably see you right as to point up anything which may harm you over the medium term? Obviously we don't know about even common drugs their long long term effects but I mean to place it the 'probably as safe as its close relatives' category.

I mean we are talking about relative risk here. I was thinking recently for example that even 'healthy' hobbies can leave you with permanent damage like having a push cycle accident. even violin gives you arthritis eventually. You're gonna be fucked either way when you are old so that isn't really the issue but rather the medium term.

The other issue would be addiction potential which seems to be boding well so far from other reports as some people have been taking it a few months and say it is on par with baclofen.

 

[deruyityn]

So to be clear are these two different substances:

4-Amino-3-(4-fluorophenyl)butanoic acid hydrochloride, 4-Amino-3-(4-fluorophenyl)butyric acid, Fluorophenibut HCL, F-Phenibut, Fluoribut, Fenibut

3-(p-tolyl)-4-aminobutyric acid (or β-(4-methylphenyl)-GABA)

Because the latter has some research already done on it being an offshoot of phenibut from the russians.

And are any of these substance from the image in this link the substance in question?

 

[Solipsis]

are any of these substance from the image in this link the substance in question?

Nope, not a fluoro in sight

'baflufen' anyone Ahh reminds me of the Daffy Duck pronouncing flephedrone days

 

[deruyityn]

Are this guy's statements accurate/valid?

His scientific knowledge sounds very impressive however many are calling him out as a fraud on that very same thread.

He said some quite reassuring things about the substance so I would not want to go believing him if it turns out it was bullshit.

 

[Solipsis]

I'd say he uses some poor reasoning, so I'd take it with a grain of salt.. for example:

Interesting that you brought up Fluorophenibut (F-Phenibut). I did some in-vivo self-sampling of this particular substitution a several months ago, when it first started to appear online. In my opinion, it is much more Baclofen-like than Phenibut-like. (Which to me means very limited activity). I tried a 50mg oral dose, but did not do anything to attempt and analyze it's absorption or metabolism. Remember that Baclofen is just a Phenibut molecule with a chloride atom attached to the ^3 position of the molecule's cyclic phenyl ring. Since a fluoride group is a halogen, just like Baclofen's chloride group, it makes sense that they should have similar oral bio-availability, binding affinities, and metabolism. The reason that Phenibut doses have to be so large is that the molecule goes through such extensive first-pass metabolism in the stomach, and most of it is destroyed before it is absorbed. However, the addition of that single little chloride atom on Baclofen significantly protects it's molecule from extensive first-pass metabolism in the stomach. (Just think, 1000mg doses are typical for Phenibut, while 20mg doses are typical for Baclofen). Since Flourophenibut also contains a halogen group (in this case, a flourine atom), it should be expected that the oral absorption should be on the higher side (like Baclofen), but perhaps not quite as great, since the fluoride group basically behaves like an oddly-shaped hydrogen atom - it may be susceptible to several digestive enzymes and/or enzymatic proteases in the stomach. Still, the doses required should be significantly lower than required for Phenibut.

A lot of this is already touched on in this thread like the fluoro indeed protecting against metabolism of the para phenyl position. And yes the fluoro group has some things in common with a hydrogen, but it's the modest radius rather than the rest (electronic properties mostly) so the opposite of what is suggested. It is however difficult to say what the impact is on affinities of hepatic enzymes (proteases have nothing to do with this, there are no protein ligands involved - one of several instances that make him sound interesting, but unfortunately inaccurate or unsubstantiated claims are made instead). It completely depends on the kind of preferences these enzymes have, the lipophilicity can be one of the factors... but either way, the C-F bond is definitely not so easily broken as when it were just a hydrogen so even if the affinity for the enzymes is more or less unchanged don't expect metabolism to be happening there.

I am surprised that I haven't seen more on the online forums about Fluorophenibut, yet. Once, while giving a lesson on amino acids to one of my younger cousins who is interested in biochemistry, we synthesized another pretty closely-related compound to Baclofen - namely Bromophenibut - one that I have not seen anywhere in the literature, even though it probably has been synthesized before, and I probably cannot take credit for it's discovery. (We didn't try it in-vivo or in-vitro (either animal or human models), as very little was produced, just for demonstration). Bromide groups are halogens, just like the fluorine group on Fluorophenibut, and the chloride group on Baclofen, so they most likely all have fairly similar Baclofen-like pharmacological actions. As far as specific affinities for GABA Receptors, as well as their oral bio-availability and metabolism, there are likely some slight variations.

Although, it is important to note, that Phenibut generally provides much greater anxiety relief than Baclofen in most people, because Baclofen only possesses one of Phenibut's three mechanisms-of-action that promote anxiolysis. (And, this is probably true for Fluorophenibut, in most people). The same chloride atom that protects Baclofen in the stomach and increases it's oral bio-availability so much, also means that unlike Phenibut it does not possess any noteworthy affinity for the a2o-subunit-containing Voltage-Gated Calcium Channels that Phenibut does. (Another mechanism-of-action by which Phenibut produces it's anxiolytic action). Also, that same addition of the chloride atom of the phenyl ring of Baclofen appears to nullify all affinity for the TAAR1 (Trace-Amine Associated Receptor), which Phenibut does possess - where it antagonizes the action of the body's endogenous B-phenythylamine (which can promote anxiety, and is the chemical backbone for many drugs like amphetamines and some substituted cathinones, which can induce anxiety), this being the third mechanism by which Phenibut achieves it's anxiolytic effect. I don't know if Fluorophenibut will really catch-on or not, basically just being an ultra-simple functional Baclofen substitution. The 50mg dose (free amino-acid form) that I took didn't do much at all, and very much seemed typically Balofen-like to me. Time will tell how the majority of the research chemical testers will react to it. If nothing else, it may be a more readily-available way for some individuals to obtain it over prescription Baclofen tablets. As far as safety goes, Fluorophenibut is just a substitution of one functional halogen group for another - (the chloride group in Baclofen, and the fluorine group in Fluorophenibut), which behave very similarly chemically, so safety should be comparable. (Unless maybe in the case of LD50 (Lethal Dose 50%) studies, where one might be slightly more potent, but that's probably splitting hairs unless you are ingesting grams upon grams of either one).

As far as I know it is not really confirmed whether GABA_B agonism is even that relevant anymore at doses phenibut is active at. The calcium channel blocking effect was not that long ago discovered to be significant and may very well be the most significant mechanism of action altogether. Even if phenibut has three mechanisms of action, it's doubtful that all three contribute as significantly to its anxiolytic effects. Instead it seems more reasonable to consider it as being primarily a VDCC blocker while baclofen is known to be primarily a GABA_B agonist.

I would tentatively agree that the analogy of phenibut > F-phenibut > baclofen bodes well for it's safety, as you would expect that F-phenibut is relatively similar to one of the others, which as has been posted is thought to be baclofen... unfortunately assumptions sometimes turn out to be wrong just like it was a surprise that phenibut doesn't really act the same as baclofen or GABA, it would be quite an astonishing surprise if F-phenibut turns out to have yet another mechanism of action than all of the aforementioned, ridiculous to consider even, yet we should always be careful to not run with our assumptions.

So in summary it seems probable that it follows the analogy to baclofen in a lot of ways, I say that because it is argued convincingly in this thread, and who knows some of its properties may turn out to lie closer to those of phenibut than baclofen... but I feel that this guy is assuming too much. Also I'm quite opposed to the impression he gives that some atom can be considered to give the whole molecule a certain property, the whole issue with SAR is that you have to consider the entire molecule per situation... but maybe the fault is in my interpretation of his post, I don't know.

 

[deruyityn]

Thanks for the analysis .

Ye I am most interested in the safety predictions he mentions which you tentatively agree with. I mean if it is probably relatively safe then the rest can be found out in time through in vivo testing eh? Though it is useful to get an idea of the voracity of his other claims to get an idea of how much credence to give to perhaps future things anyone may come across from the fellow.

I'd say he uses some poor reasoning, so I'd take it with a grain of salt.. , I don't know.

 

[Solipsis]

Veracity yeah.. as long as you remember the apprehension of concluding things about the metabolism, toxicology etc. You never know what enzyme a drug be fucking with for example, so trying to decide whether a compound is a particularly bad idea to ingest is one thing, but you will still always have to accept the potential risks and side effects that have yet to surface.

Plus, it's best if others with different and/or more background chime in before anyone makes any rash decisions, I've been plenty wrong before in this very thread.

Anyway, if you want to know the novelty of this title compound is not really threatening to me... but I'd personally think twice before taking anything baclofen-like unless I have very good reasons.

 

[deruyityn]

Hmm well it has been out around 6 months now and nothing untoward has been reported so far.

I spoke to a guy on a forum who has taken loads of it and has been taking it several times a week for the last few months with no ill effects to report.

Of course sample size of one is not worth much however I have heard the same reports from around the net that is quite pedestrian in nature so far in terms of side effects.

Sure 6 months isn't long but doesn't that equate to a decent sized clinical trial when a new chemical is tested on humans by a pharmaceutical company?

Of course it isn't as scientifically robust but still surely that is a decent enough sample size to get an idea that it is probably ok ...right?

Veracity yeah.. as long as you remember the apprehension of concluding things about the metabolism, toxicology etc. You never know what enzyme a drug be fucking with for example, so trying to decide whether a compound is a particularly bad idea to ingest is one thing, but you will still always have to accept the potential risks and side effects that have yet to surface.

Plus, it's best if others with different and/or more background chime in before anyone makes any rash decisions, I've been plenty wrong before in this very thread.

Anyway, if you want to know the novelty of this title compound is not really threatening to me... but I'd personally think twice before taking anything baclofen-like unless I have very good reasons.

 

[Solipsis]

Experience report:
https://www.erowid.org/experiences/exp.php?ID=108165

A little background--I am a several year user of Phenibut, have developed a mild tolerance, and take about 2 to 2.5 grams (20mg/Kg) every other day. The dopaminergic 'mood enhancing' effects have long faded away, but the anxiolytic effects have remained strong. My tolerance has gone both up and down at times, though I have always used the same supplier. On occasion when I've skipped doses or taken breaks I've had mild withdrawals, chiefly anxiety, depression, and insomnia, rarely lasting more than five days. The only side effect I've noticed are occasional extremely vivid and detailed dreams that feel completely real while they are happening (though no awareness that one is dreaming, alas.)

Losing the magic but not the anxiolytic effect is normal for gabapentinoids. Has nothing much to do with GABAergic or dopaminergic effects, gabapentinoids act differently.

The overall experience was very similar to my usual 2 gram dose of Phenibut, except all crammed into a few hours instead of a day and a half. The faster onset indicates more rapid crossing into the brain and the shorter duration may indicate more rapid metabolism. The approximate 8-10x increase in potency means less drug to take, but with something like this it's not that important. The dopaminergic rush was light but very pleasant, and is likely to wear off with repeated use.

Similarly to phenibut (β-phenyl-GABA), as well as pregabalin (β-isobutyl-GABA), which are close analogues of baclofen, baclofen (β-(4-chlorophenyl)-GABA) has been found to block α2δ subunit-containing voltage-gated calcium channels (VGCCs).[25] However, it is weaker relative to phenibut in this action (Ki = 23 and 39 μM for R- and S-phenibut and 156 μM for baclofen).[25] Moreover, baclofen is in the range of 100-fold more potent by weight as an agonist of the GABA_B receptor in comparison to phenibut, and in accordance, is used at far lower relative dosages. As such, the actions of baclofen on α2δ subunit-containing VDCCs are likely not clinically-relevant

So it seems unclear whether the VDCC / VGCC blocking effect F-phenibut is likely to have at some eventual dosage level is perhaps relevant whereas for baclofen it isn't.

Euphoria and anxiolysis are still expected for F-phenibut even if it is just basically a GABA_B agonist like baclofen is considered to be. Will have to wait and see if it can just as much make you dizzy and wobbly-footed, relax muscles and make you black out if used incorrectly.

I would be rather careful with F-phenibut and for the time being assume that taking too much isn't as benign but just possibly shitty feeling as some gabapentinoids, but can be an issue.

As for the report: I don't think taking a GABAergic 2 days after discontinuing phenibut, for just a day, says anything about it actually substituting for the gabapentinoid effects. A GABAergic can suppress withdrawal of gabapentinoid VDCC blockers. So I think the report can be misleading if anyone would try to draw such conclusions.
I don't really expect F-phenibut to be an effective VDCC blocker, but the point is that we can't really predict it and this report doesn't prove anything.

 

[serotonin2A]

Hmm well it has been out around 6 months now and nothing untoward has been reported so far.

I spoke to a guy on a forum who has taken loads of it and has been taking it several times a week for the last few months with no ill effects to report.

Of course sample size of one is not worth much however I have heard the same reports from around the net that is quite pedestrian in nature so far in terms of side effects.

Sure 6 months isn't long but doesn't that equate to a decent sized clinical trial when a new chemical is tested on humans by a pharmaceutical company?

Of course it isn't as scientifically robust but still surely that is a decent enough sample size to get an idea that it is probably ok ...right?

Even if a drug can produce severe adverse reactions, that doesn't mean that such effects occur in all patients. Plus, how would these individuals know if they had sustained hepatotoxicity, renal damage, cardiovascular toxicity, fibrosis, an elevated risk for cancer, etc? They are monitoring themselves for obvious signs of toxicity, but they have no way to detect many other types of adverse drug effects.

 

[deruyityn]

I would be rather careful with F-phenibut and for the time being assume that taking too much isn't as benign but just possibly shitty feeling as some gabapentinoids, but can be an issue.

Rather convoluted sentence. Why are you saying you would be rather careful? I have read nothing online so far about deleterious effects of this product so what is your opinion based on? You are implying it is worse than just normal baclofen. Or you just meant the average caution when approaching any new substance?

In the experiences thread I linked in post #11 there was a guy who took 1.5 grams of it by being careless. He had a bad time of it but recovered ok.

 

[Solipsis]

I'm saying that even if it is comparable to baclofen it doesn't seem half as suitable to me for the general public as phenibut is.

I agree with serotonin2a's sentiment about the "it should be okay right?" attitude: the analogy to baclofen for general pharmacology and as well to phenibut to any other possible toxicology don't make anyone here say that right off the bat the carcinogenic / cytotoxic properties are predictable, but that doesn't mean you shouldn't be on your guard.

Look, I will immediately admit that at some point I was eager to try RC's and I had a lot to learn personally as well as about chemistry and all that other business. Now years later I am not that experimental anymore and feel that back then it blinded me: it was interesting and exciting. Potential risks didn't occur to me as clearly as they did later. But being among the first to take a compound will always be pretty tricky, and people shouldn't focus on the "probably alright" part, but on the weird flukes like phenibut turning out to act so differently as we thought.

It's always fucked up to find out what people get themselves into without knowing it...

If F-phenibut is comparable to baclofen, are you interested in taking it? Because as much as I appreciate phenibut, I sure as shit wouldn't take baclofen for random reasons even if people "recover ok" from it.

 

[deruyityn]

If F-phenibut is comparable to baclofen, are you interested in taking it? Because as much as I appreciate phenibut, I sure as shit wouldn't take baclofen for random reasons even if people "recover ok" from it.

well people have been saying that baclofen is just a more sedating version of phenibut without the dopamine push. Seems you are against all drugs; are you a reformed t-totaller or what. I've had several years of abstinence and I was probably worse off mentally when I had no release from the humdrum kafkaesque (learned what that meant yesterday so wanted to drop it in ) existence and I choose to take careful therapeutic doses of drugs if I think they will help me. I don't see the problem there. Kratom has been great and I am not out on the street pan handling. I was actually wondering if, since flourphenibut is verging more on the baclofen side, it wouldn't be a better choice to just take baclofen since it is pretty easily available and is alot better studied.

Although the low overdose threshold is concerning.

I want something that isn't too addictive for anxiolystic and hypnotic effects (if I take low doses of speed again). No not for every day use but just to use as needed or once a week or so as phenibut is used. I don't want to try phenibut due to the extreme withdrawal curve. Flourophenibut seemed more acceptable to me but maybe baclofen is better again since it seems very similar structurally to phenibut and doesnt last long and has lower dependency issues?

I haven't seen outrageous report of baclofen either which is why I'm confused by your statements. Most people use baclofen to get off other drugs and taper easily off it so I don't see why you're bashing it. I never tried it but the wealth of reports I've read contradict your negative attitude towards it.

and no1 dare mention antihistamines to me. Find those things disgusting and only induce a state of delirium.

 

[Anxious.Individual]

well people have been saying that baclofen is just a more sedating version of phenibut without the dopamine push. Seems you are against all drugs; are you a reformed t-totaller or what. I've had several years of abstinence and I was probably worse off mentally when I had no release from the humdrum kafkaesque (learned what that meant yesterday so wanted to drop it in ) existence and I choose to take careful therapeutic doses of drugs if I think they will help me. I don't see the problem there. Kratom has been great and I am not out on the street pan handling. I was actually wondering if, since flourphenibut is verging more on the baclofen side, it wouldn't be a better choice to just take baclofen since it is pretty easily available and is alot better studied.

Although the low overdose threshold is concerning.

I want something that isn't too addictive for anxiolystic and hypnotic effects (if I take low doses of speed again). No not for every day use but just to use as needed or once a week or so as phenibut is used. I don't want to try phenibut due to the extreme withdrawal curve. Flourophenibut seemed more acceptable to me but maybe baclofen is better again since it seems very similar structurally to phenibut and doesnt last long and has lower dependency issues?

I haven't seen outrageous report of baclofen either which is why I'm confused by your statements. Most people use baclofen to get off other drugs and taper easily off it so I don't see why you're bashing it. I never tried it but the wealth of reports I've read contradict your negative attitude towards it.

and no1 dare mention antihistamines to me. Find those things disgusting and only induce a state of delirium.

Baclofen's overdose threshold is lower than that of opiates and barbiturates. Neither phenibut or baclofen are recreational, however baclofen is far more pleasant and is a superior anxiolytic, and it's longer acting than phenibut. I find 125mg-150mg to be an effective dose, however it has the most horrific withdrawal I've ever experienced, it feels like going through benzo and opiate wd at the same time, +extra psychosis and visual hallucinations.

 

[deruyityn]

Neither phenibut or baclofen are recreational, however baclofen is far more pleasant and is a superior anxiolytic, and it's longer acting than phenibut. I find 125mg-150mg to be an effective dose, however it has the most horrific withdrawal I've ever experienced, it feels like going through benzo and opiate wd at the same time, +extra psychosis and visual hallucinations.

baclofen is much shorter half life from what I read, both anecdotal and from medical literature, and plenty of people would disagree with you about phenibut not being recreational. Sounds like you must have been an every day fellow to get withdrawal and looking for some extreme high seeing as you sound like you have been around the block with opiates and benzoes.

It reminds me of career heroin addicts complaining that kratom 'does nothing'.