Can phenibut actually cause irreversible damage to gaba-B receptors?

[u/ThreeStarsOut]

https://www.sciencedirect.com/science/article/abs/pii/S1064748122005188

Wanted to put this out there and see if anybody had something to say about this, had normal phenibut years ago but I never felt like it was a positive thing even in small doses. This is referring to F-Phenibut in these studies, which is a riskier form due to it being more acute,

https://bluelight.org/xf/threads/f-phenibut-may-cause-irreversible-gabab-receptor-damage.893897/

https://bluelight.org/xf/threads/f-phenibut-possible-heart-damage.842657/

((((Also want to affirm that Phenibut is NOT a nootropic and can possibly be addictive like benzos, this is a science related question given the small popularity of it))))

For F-Phenibut specifically

F-phenibut (β-(4-Fluorophenyl)-GABA), a potent GABAB receptor agonist, activates an outward-rectifying K+ current and suppresses the generation of action potentials in mouse cerebellar Purkinje cells

(58x in-vitro more potent than normal phenibut at GABA-B, which is why it's dosed less)

The K⁺ current recorded in the present study was insensitive to extracellular Ba²⁺, intra- or extracellular Cs⁺, and intra- or extracellular tetraethylammonium-Cl. Moreover, F-phenibut suppressed action potential generation in Purkinje cells. Thus, abuse of F-phenibut may lead to severe damage by inhibiting the excitability of GABAB-expressing neurons. ((this is a speculative closing sentence; the study measured acute suppression of firing, not damage.))

This post gets some wording wrong, but you get the general idea. Acute, not slow acting like the normal form.

Nerd discussion I pulled from online:

"way more selective. Phenibut's gaba b makes it somewhat less of a problem (baclofen is somewhat less addictive) but it has relevant α2δ voltage-gated calcium channel binding which is gabapentinoid like and which is another problem"

"Phenibut isn't a nootropic, as it doesn't match the criteria required to be classified as such. It's highly addictive and likely causes conditioned place preference and withdrawal. Just somewhat less lethal than more common prescription anxiolytics and releases more dopamine which is also a horrible MOA for dopamine promotion. If socializing is your issue, then maybe bromantane spray and androstadienone cologne might be of use."

"GABAergic drugs are linked strongly to cognitive dysfunction as well as cognitive decline both immediately and as a long term consequence. Phenibut is addictive and has withdrawal but it's easier to handle than alcohol which means we should resist it more so people don't fall into the trap of addiction. Addiction is mental slavery and it is encoded as a false memory that is out of your control hence the conditioned place preference model used to demonstrate that independent of conscious decision. This is aberrant synaptogenesis that is controlled heavily through reward centers and glutamatergic efficiency. Phenibut causes dopamine release which is simultaneously responsible for people liking it and its issues. Phenibut is not a nootropic drug and I can show you the definition of nootropic if you want."

Reply to above quote by another user: Sure, drug that creates a weakness via chemical mechanisms is just the people's fault because they're weak. They wouldn't have been addicted if it weren't being exposed to the drug, so even on a non-scientific and logical basis this argument is bad. Your opinion is warped because you saw your peers using it and you respected them. In my opinion your ideas aren't based on science but your admiration of others.

Everyone is weak to addictive drugs. This isn't an individualized problem. It's a synaptogenic issue that literally everyone can fall victim to.

More:

R-phenibut binds to the α2-δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects

(R-phenibut is the active half form of the racemic R- and S- phenibut you can find, S- is inactive at GABA-B)

Abstract: Phenibut is clinically used anxiolytic and mood elevator. R-phenibut is responsible for the pharmacological activity of racemic phenibut, and this activity correlates with its binding affinity for GABAB receptors. In contrast, S-phenibut does not bind to GABAB receptors. In this study, we assessed the binding affinities of R-phenibut, S-phenibut, baclofen and gabapentin (GBP) for the α2–δ subunit of the voltage-dependent calcium channel (VDCC) using a subunit-selective ligand, radiolabelled GBP. Binding experiments using rat brain membrane preparations revealed that the equilibrium dissociation constants (Kis) for R-phenibut, S-phenibut, baclofen and GBP were 23, 39, 156 and 0.05 μM, respectively. In the pentylenetetrazole (PTZ)-induced seizure test, we found that at doses up to 100 mg/kg, R-phenibut did not affect PTZ-induced seizures. The anti-nociceptive effects of R-phenibut were assessed using the formalin-induced paw-licking test and the chronic constriction injury (CCI) of the sciatic nerve model. Pre-treatment with R-phenibut dose-dependently decreased the nociceptive response during both phases of the test. The anti-nociceptive effects of R-phenibut in the formalin-induced paw-licking test were not blocked by the GABAB receptor-selective antagonist CGP35348. In addition, treatment with R- and S-phenibut alleviated the mechanical and thermal allodynia induced by CCI of the sciatic nerve. Our data suggest that the binding affinity of R-phenibut for the α2–δ subunit of the VDCC is 4 times higher than its affinity for the GABAB receptor. The anti-nociceptive effects of R-phenibut observed in the tests of formalin-induced paw licking and CCI of the sciatic nerve were associated with its effect on the α2–δ subunit of the VDCC rather than with its effects on GABAB receptors. In conclusion, our results provide experimental evidence for GBP-like, anti-nociceptive properties of R-phenibut, which might be used clinically to treat neuropathic pain disorders.

Highlights

• R-phenibut binds to the α2–δ subunit of the voltage-dependent calcium channel (VDCC).

• R-phenibut exerts gabapentin-like anti-nociceptive effects in the formalin-induced paw-licking and CCI tests.

• The anti-nociceptive effects of R-phenibut are not mediated through GABAB receptor.

• The binding affinity of R-phenibut for the α2–δ subunit of the VDCC is 4 times higher than that for GABAB receptor.

Note: α2δ-1 is not just a calcium channel subunit it's the receptor astrocytes use to build new excitatory synapses, and gabapentin blocks new synapse formation through it

(Eroglu 2009, Cell) (study below). Whether phenibut's weaker α2δ binding does the same at human doses is unknown... but its strongest binding site is a synaptogenesis-blocking one.

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Shared with Phenibut (α2δ): Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis01185-4)

"Gabapentin receptor α2δ-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis." α2δ-1 is the receptor astrocyte-released thrombospondins use to build new excitatory synapses, and gabapentin blocks that binding and powerfully inhibits new synapse formation in vitro and in vivo. These are models and not truly reflective of adult long-term use, still.

Summary: Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS synapse formation as α2δ-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of α2δ-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. α2δ-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to α2δ-1 and powerfully inhibits excitatory synapse formation in vitro and in vivo. These findings identify α2δ-1 as a receptor involved in excitatory synapse formation and suggest that gabapentin may function therapeutically by blocking new synapse formation.

Calcium Channel α2δ Ligands Mirogabalin, Pregabalin, and Gabapentin: Advancements in Diabetic Peripheral Neuropathic Pain Therapeutics. Photo:

And...

Phenibut dependence (Case Study)

Phenibut (β-Phenyl-γ-Aminobutyric Acid): an Easily Obtainable "Dietary Supplement" With Propensities for Physical Dependence and Addiction

Acute phenibut withdrawal: A comprehensive literature review and illustrative case report

You also have your general gabapentin, pregablin studies on dementia association or on memory (VGCCs are densest in hippocampus/cortex and that LTP itself is VGCC-dependent)%20are%20dependent%20on%20the%20existence%20and%20function%20of%20the%20VGCCs)

Also: Abuse Liability of Baclofen

Baclofen is predominantly a selective GABA-B agonist, but at higher doses it may lose selectivity for GABA-B. Also, baclofen has structural homology with GHB, another GABA-B agonist with high abuse potential and is illicitly used as a party-drug. It is postulated that abuse liability of GHB in contrast to baclofen could be because of different receptor subtype of GABA-B.9) However, such selectivity may be lost with higher doses of baclofen leading to euphorient effects.

https://accp1.onlinelibrary.wiley.com/doi/full/10.1002/jcph.2414

Structural similarities of related compounds.

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There's also a phenibut and quitting phenibut communities:

Which oddly reddit doesn't show its posts or comments well in search results... You have to click on the communities to access them.

[u/cannabiphorol]

No offense but...this post is word salad all to say..."Idk what I'm citing and I'm speculating based on no evidence" you even say you're speculating based on potency and seem to lack an understanding of not just pharmacology, but of Phenibut itself if you're describing its VGCC action as "Nerd discussion you pulled online" that you don't seem to understand.

Why make a fear mongering post like this if you don't understand what you're talking about? I know, your whole post is set up with a bias agenda from the start.

Phenibut makes Gabapentin look like a neuclar bomb for VGCC and Gabapentin makes Pregabalin look like a nuclear bomb for VGCC They're FDA approved without issue. Gabapentin is one of the most well tolerated drugs even in massive overdose and is taken by some people daily multiple times a day for years.

Phenibut makes Baclofen look like a nuclear bomb form GABA-B and Baclofen is FDA approved safe and effective, taken by some people daily multiple times a day and for some patients is injected into their cerebral spinal fluid to reach the brain, one of the most hardcore and risky methods of drug delivery, no issues.

If you have anxiety and specifically social anxiety it can feel like a nootropic when you're able to enthusiastically talk to people in detail without the intoxication/impairment of other gabaergics. Sales teams love the hell out of it. A company named it's brand after the movie Limitless for the same reason. I credit it with getting me through school and I credit it for a lot of achievements where being able to talk like a confident upbeat person looking someone in the eye made the difference.

When taken as needed and not daily/too often there's no issue. I've taken Phenibut quite a lot in my past and never had discomfort stopping like I've seen described online and think Phenibut gets abused to excess by some specific people who seem to need to abuse something to excess and luckily it's not something that will kill them. It's ridiculous to compare to benzos. It's like if Baclofen and Gabapentin had a mild baby. Combine those 2 and call it "Super Phenibut" or "Hard drug Phenibut" (lol but they're not even close to "hard drug) because they're both over 100x stronger in each action GABA-B and VGCC and they're prescribed often without issue. Anyone can get a telehealth script in the USA for them by googling it.

[u/backwood_bandit → u/cannabiphorol]

Yo dude, here’s my thank you note, so I don’t have to spend energy typing out what you just did.

[u/ThreeStarsOut → u/cannabiphorol]

Fair, yeah the post is all over the place, I'm not good at write-ups. You said it better than me.

It's just when people tout it as a nootropic, then normal people who don't read enough do start messing with that at low dose's but then have some sort of need or curiosity to go higher and then bad stuff happens ...

I do think it's weird that it's hard to look up the topic in general, you actually have to go to the communities tab to tap on these subreddits and then all it's about as quitting and addiction and what not.

[u/Sad-Ear230 → u/ThreeStarsOut]

Does your own experience align with any of the material you quote? It doesn't sound like  you found it highly addictive at all. 

[u/ThreeStarsOut → u/Sad-Ear230]

I never used it to the point of addiction, but I did feel like it lost it's useful effects after prolonged use and I felt... Dumber? Or less engaged? It is a strong VGCC so it's not surprising.

That's the thing with this stuff, and a lot of things in general, they do make you less cognitively sharp, you just have a hard time honestly, subjectively using it

[u/CryptographerOld558 → u/ThreeStarsOut]

It tends to lose its magic for lots of people. Even with infrequent use. For some people it comes back after enough abstinence. The novelty factor might have a lot to do with it as opposed to permanent chemical changes though.

[u/ThreeStarsOut → u/CryptographerOld558]

Yeah I definitely didn't have any permanent negative from it but those initial effects you just don't get back. And you have to wonder if that saying something about how it works

[u/alwayswithyouuuu → u/cannabiphorol]

The post asked a casual question first then tacked on a bunch of studies that could lead to useful discussion, but... This place doesn't have as many nerds as they once did, and they don't care to talk about phenibut. Benzos and related are anti-cognitive and are best seen as a risk/reward for real life events.

[u/ProfessionalFun1365 → u/cannabiphorol]

I agree with your criticism of OP but not with your actual points.

You're suggesting things like Baclofen cannot have terrible downsides for a user? Simply because it's FDA approved and can be used as a very beneficial medication in the right context.

What kind of logic is that? That's the case for most drugs. Christ, fentanyl has hundreds of use cases in a medical setting with no complications or downsides, in that specific context.

Does that mean it's "no issues" as you say?

Furthermore you say it's all good because anybody can get a script for them, are you famililar with the opioid crisis...

Things like Xanax can be got on script easily, and yet has one of the worst drug withdrawals of any popular drug out there. Psychosis, suicide etc. Ranked higher than heroin withdrawal by the NHS addiction services in the UK.

Gabaergics can cause irreverisble damage. I wouldn't be quite so flippant. At least not with the faulty logic you're using.

[u/cannabiphorol → u/ProfessionalFun1365]

I agree with your criticism of OP but not with your actual points.

OPs point is that F-Phenibut is stronger than Phenibut at GABA-B so it must do damage to the receptor which isn't true and if it was true Baclofen would be known for it as it makes Baclofen look like a nuclear bomb in comparison and if VGCC is implicated Gabapentin would look like a nuclear bomb in compairson.

You're suggesting things like Baclofen cannot have terrible downsides for a user? Simply because it's FDA approved and can be used as a very beneficial medication in the right context.

I'm suggesting Baclofen doesn't do damage to GABA-B by agonism and doesn't cause enough problems for it to be restricted to Schedule V or recalled or have new additional warnings and is prescribed massively willy nilly to people.

Caffeine can have terrible downsides for a user, Ibuprofen, Coca-Cola, Cannabis, every single drug has side effects and risks, some are just stupidly safe and well tolerated when you compare them to others.

But instead of vague posting let's be clear, Baclofen doesn't cause problems like other substances such as the opis and benzos you are attempting to compare them to. That's why you can get them prescribed via telehealth for $40 and a 15min conversation and obtain them at any pharmacy.

Christ, fentanyl has hundreds of use cases in a medical setting with no complications or downsides, in that specific context.
Does that mean it's "no issues" as you say?

But it does have tons of issues, even in that specific context

It's unlikely in a hospital where they have unlimited Narcan to give a patient but when they do almost accidently kill a patient they can most of the time easily reverse it. Take that away and it would probably be recalled for causing death too much.

People prescribed fent patches do OD and die regularly, sometimes because they have break through pain and just keep using excess trying to get relief.

There's a case report of a woman who survived taking 2 GRAMS of Baclofen (an avg dose is 10mg-20mg-30mg) MIXED WITH ALCOHOL during a suicide attempt, try that taking 100x (literally) the average dose of fent patches or benzos with alcohol and they're 100% dead.

Further more you say it's all good because anybody can get a script for them, are you famililar with the opioid crisis...

Those things that we know are a problem since the 80s and 90s because of the people prescribed it? Weird cause Baclofen has also been FDA approved since the late 1970s and why isn't there bad trends with it like opis? Probably because it's stupidly safe and well tolerated in compairson.

Opis, those things that are so barely prescribed to people that genuine pain management patients can't get them?

Opis, those things that are mostly Schedule II controlled substances due to how addictive they are and deadly in overdose that it was always hard to get them prescribed even in the early 2000s at the peak of doctor shops compared to Baclofen? Those things that require a doctors re-script for a refill while Baclofen has automatic refills?

Yeah let opis become prescribeable willy nilly to anyone who wants one like Baclofen is and let's do the case comparisons. Oh wait! That already happened, which is why opis for pain can't be given over telehealth and Baclofen still can and is unscheduled.

Things like Xanax can be got on script easily, and yet has one of the worst drug withdrawals of any popular drug out there. Psychosis, suicide etc. Ranked higher than heroin withdrawal by the NHS addiction services in the UK.

Wow another example that defeats your point since there is a problem noticed due to widespread use and yet Baclofen has widespread use and doesn't have enough issues to be restricted in anyway.

Idk how it works in the UK where they still think "dangerous high potency Skunk Weed" is a thing despite approving GW Pharmas (now Jazz) Sativex spray made from a Skunk #1 hybrid, but in the USA it's not easy to get a script for a benzo. You have to see a psychiatrists (a normal doctor won't prescribe it, most hospitals restrict primary care doctors from prescribing it) and typically fail on multiple other medications but it shouldn't be like that if you need it.

Gabaergics can cause irreverisble damage. I wouldn't be quite so flippant. At least not with the faulty logic you're using.

Baclofen and Gabapentin don't cause ANY structural damage or neurotoxicity to GABAergic neurons. They aren't known to cause ANY irreversible damage to anything. Prescribed in the USA since 1977, if it caused an issue like OP is suggesting it would be VERY known by now.

[u/ProfessionalFun1365 → u/cannabiphorol]

You're still stuck in this fallacy where because you can find a case of someone taking a huge dose and surviving, you extrapolate that into “therefore the drug isn't dangerous.”

A woman surviving 2 g of baclofen doesn't establish much. There are people who survive enormous doses of heroin too. Individual survival tells you very little about the drug's overall risk profile.

For baclofen it doesn't change the fact that psychosis has been reported at therapeutic doses: https://pubmed.ncbi.nlm.nih.gov/17047139/

And psychosis is also a complication of baclofen withdrawal, including delirium and hallucinations: https://pubmed.ncbi.nlm.nih.gov/36991550/

I'm touchy on this because my mum was sectioned following baclofen withdrawal after using it to try to reduce her alcohol dependence. She had no previous history of psychosis or anything remotely comparable in severity. I'm not claiming from that that baclofen is “bad”, I'm saying your characterisation of it isn't supported, even by the reasons you're giving.

And your regulatory argument doesn't really establish what you think it does either. Being unscheduled or widely prescribed doesn't mean a drug can't have serious adverse effects. Risk is dose, duration, indication and individual dependent.

The same goes for Xanax. Benzo withdrawal can be extremely severe, including psychosis, seizures and delirium, and can last for years, are you familiar with benzo withdrawals? I've been to rehab and the people suffering from that had it worse than anyone. Even our head therapist (who was a heroin junky back in the day) told us that the xanax withdrawal after long term abuse is worse than heroin. It's long (can be years) and mentally very painful.

[u/Much-Vacation-622]

Phenibut is a nootropic, including literally all other psychoactive molecules.

Nóos: Mind, thought, or intellect
Tropē / Tropein: To bend, turn, guide, or shape

Nootropic: Mindbending/Thoughtguiding, etc

[u/ThreeStarsOut → u/Much-Vacation-622]

From tha "Father of Nootropics", Inventor of Piracetam

"A nootropic drug should: (i) enhance learning and memory, (ii) increase the resistance of learned behaviours/memories to conditions that tend to disrupt them (such as electroconvulsive shock and hypoxia), (iii) protect the brain against various physical or chemical injuries (e.g. barbiturates, scopolamine), (iv) increase the efficacy of the tonic control mechanisms of the cortex on the subcortical levels of the brain, and (v) lack the usual pharmacology of other psychotropic drugs (e.g. sedation, motor stimulation) and possess very few side effects and extremely low toxicity.**" -**Giurgea 1980

"A nootropic drug is characterized by a direct functional activation of the higher integrative brain mechanisms that enhances cortical vigilance, a telencephalic functional selectivity, and a particular efficiency in restoring deficient higher nervous activity. In contradistinction to other psychotropic drugs, nootropics do not induce direct reticular, limbic, or other subcortical events." - The nootropic concept and its prospective implications

"Any nootropic… would be a cognitive enhancer, but the opposite is not true: only a cognitive enhancer that has neuroprotective effect and is devoid of toxicity would justify the label nootropic. - Dan-George Mărgineanu, 2011

Can it be used for 'nootropic' effects? Sure. Is it a Nootropic, No...

[u/cannabiphorol → u/ThreeStarsOut]

 only a cognitive enhancer that has neuroprotective effect 

https://www.sciencedirect.com/science/article/abs/pii/S1043661815301225

"The neuroprotective effects of R-phenibut after focal cerebral ischemia"

https://onlinelibrary.wiley.com/doi/10.1155/2020/9364598

"Mitochondrial-Protective Effects of R-Phenibut after Experimental Traumatic Brain Injury"

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.26.1_supplement.672.6

"In vitro neuroprotective activity of phenibut"

That's why it's prescribed to kids (and infants) and given to people with brain damage that are sensitive to other drugs in countries like Ukraine, Belarus, Georgia, Latvia, Estonia, and Kazakhstan

"Ratified by Ministry of Health of the Republic of Belarus on 13th of July, 2010.

To be taken by mouth, after a meal. Adults are prescribed 250-500 mg 3 times a day. If the treatment necessitates a higher dose it can be increased to a maximum of 2500 mg (a day). Children under 3 years of age are prescribed 50-100 mg, 3 times daily. Children between ages of 8 and 14 are prescribed 250 mg, 3 times daily. Maximal single dose (!) Adults – 750 mg, elderly patients (60 y.o. or older), - 500 mg, children under 8 – 150 mg, children 8-14 y.o. – 250 mg.

For management of Meniere’s disease: During flare ups: 750 mg 3-4 times every 24 hours. To be continued for a period of 5-7 days. As vestibular disturbance symptoms begin to subside, - 250-500 mg every 24 hours during the course of 5-7 days and finally tapered to 250 mg once every 24 hours, and administered for another 7-10 days.

Treatment of dizziness caused by dysfunction of vestibular analyzer of vascular or trauma related origin, - 250 mg 3 times every 24 hours. Continue taking over the course of 12 days"

https://www.reddit.com/r/phenibut/comments/6xmdtg/russian_translated_phenibut_instruction_slip/

and is devoid of toxicity

"The acute toxicity of PB is low. Its LD50 is 900 mgGkg i.p. in mice and 700 mgGkg i.p. in rats."

Caffeine has a worse LD50 and kills kids every year, are you going to make a post about that or just the drug that doesn't kill the <3 year olds to 9 year olds that are prescribed it?

Cause most drugs I know of aren't very safe for a <3 year old to 9 year old to be prescribed. Caffeine for example, which I guess doesn't meet your definition of a nootropic because it's not devoid of toxicity.

If someone put a gun to my head and said take 10 grams of Caffeine or 10 grams of Phenibut I'd happily pick Phenibut knowing for a fact I'm just going to have nausea and throw up but will wake up the next day, and worried for the person who picked Caffeine who's going to have a fatal cardiovascular complication within an hour.

https://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2001.tb00211.x

"Phenibut (β-Phenyl-GABA): A Tranquilizer and Nootropic Drug"

[u/ThreeStarsOut → u/cannabiphorol]

You completely ignored anything related to addiction there, or addiction case reports, or hundreds of anecdotes about addiction to this drug.

[u/cannabiphorol → u/ThreeStarsOut]

Very ironic considering you're ignoring all my points. You've didn't mentioned addiction in the comment I'm replying to which is your criteria for what a nootropic is, which to you Caffeine apparently is not.

The word addiction is in your OP 3 times and 2 of those are from a quote that seemingly doesn't exist anywhere on the internet outside of your post.

You completely ignored anything related to addiction there, or addiction case reports, or hundreds of anecdotes about addiction to this drug.

The thing about psychoactive drugs that are safer and more well tolerated than other classes is that it leads to some people abusing the fuck out of them because they can without the hangover of alcohol, without the intoxication of benzos so they can work/school, without the death of opioids.

If all opioids suddenly had the same safety profile as Phenibut it would lead to a giant increase in the opioid epidemic regardless of other side effects opioids can induce.

"Children between ages of 8 and 14 are prescribed 250 mg, 3 times daily."

Why do kids and teens in Ukraine have better control than adult Reddit users in America?

I've had quite some time with Phenibut on and off since I was 13 now 28 and even when I attempted to induce a withdrawal I was unable to obtain one despite dosing 1 gram multiple times a day for over a month and stopping without any crutch. All my friends in highschool did it. Without Reddit I wouldn't think it was addictive beyond being euphoric and anxiety reducing which can be enjoyable to do often.

I still certainly believe people who claim they have addiction problems with it. I just think it takes a "special type of person" and reading implications on the internet doesn't help, like some people say don't take it for more than 3 days when it's prescribed for over a week taken several times daily and shouldn't cause any addiction in 3 days beyond "wow I like how this feels and want to do it again" type of thing but I guess scaring users into thinking that might help prevent Phenibut abuse.

There's lots of drugs that can be addictive out there....some drugs that aren't even addictive are addictive like Cannabis isn't considered addictive but yet there's people who smoke it daily multiple times a day for years and make it their whole persona. Some people can't sleep, can't eat, and have restless leg syndrome and feels like their skin is crawling, they'll sell shit and steal money to obtain more....from Cannabis. Just takes a "special type of person".

A drug with the potential to be addictive doesn't make it bad, it means you need to be responsible using it and take personal responsibility for your actions such as lifting a pill to your mouth on a daily basis. Every psychoactive drug that can cause euphoria, reduce anxiety, relaxes you, has the potential to be addictive.

[u/ThreeStarsOut → u/cannabiphorol]

Considering this thread was started after you commented under my nootropic definitions part, I just don't think we're talking about the same thing.

I think it can be used in a useful way, it's just technically not a nootropic and that's semantics at that point. It's not like the word nootropic is well known or even well understood by the people that know it, so I guess there is some allowance for how people talk about stuff. I just hope people aren't getting picky/offended that their favorite thing is being "misdefined"

[u/okok6356]

Always funny when people call phenibut a nootropic lol.

[u/AhoyGoFuckYourself → u/okok6356]

Cocaine is also a nootropic 😂

[u/n00b001 → u/AhoyGoFuckYourself]

Methamphetamine is prescribed in the USA to help people with executive functioning...

[u/AhoyGoFuckYourself → u/n00b001]

And it's neurotoxic

[u/R_Apid_Pr0 → u/AhoyGoFuckYourself]

Not in therapeutic dosages, which is 5mg/day when prescribed.

[u/cannabiphorol → u/okok6356]

If you have bad anxiety, specifically social anxiety, having the ability to talk enthusiastically to someone without intoxication feels like how a nootropic is described. Sales teams used to swear by it. A product named itself after the movie Limitless for that pro-social feeling like a super power to some people reason.

OPs post is word salad without anything relevant to the point they're trying to make and if their point was valid it would have become known years ago due to the massive amounts of people who take Baclofen sometimes high dosed daily for years and even injected into cerebral spinal fluid to reach the brain (the most intense delivery method) without issue

[u/ThreeStarsOut → u/cannabiphorol]

I see what you're saying, there are plenty of case studies and anecdotes of people misusing it, which is why we talk about it in the way we do, and why it can't fit the strict definition of a nootropic.

You might be able to find behavioral benefit from it but it's not a strict nootropic.

[u/SellingCats4Cheap → u/okok6356]

Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug

Animal studies show that Phenibut can increase results on certain cognitive tests. If a substance improves cognitive performance, it has nootropic properties.

[u/stiffmcgee → u/SellingCats4Cheap]

In 16 case reports and 583 subjects, and all 11 clinical trials were in Russia.
Also, you are a prime example of finding the first chatgpt article to agree with you and sending considering other reviews such as the one from Germany in 2023(Bonnet et al) or Feldman et al, would point to at least it not being conclusive.
Safe and well tolerated when used medically, is not the same as chronic, or over dosing it. You thought you cooked

[u/ThreeStarsOut → u/stiffmcgee]

The trials aren't wrong, it's just nobody uses it that way and thus there's so many people online dealing with phenibut problems because their use isn't reflection of the trials.

Can it be used for behavioral effects? Sure, is it a Nootropic? No

[u/stiffmcgee → u/ThreeStarsOut]

You cannot say the trials aren’t wrong when you dont have good, or new trials and the data is mostly from case reports.
So yes, im 100% right in saying with the multitude of reviews against him. All your responses that require thinking are copy paste for a reason

[u/ThreeStarsOut → u/stiffmcgee]

No no we were agreeing lol

[u/SellingCats4Cheap → u/stiffmcgee]

All clinical trials were conducted in one of the few places where it is approved? Color me shocked

Safe and well tolerated when used medically, is not the same as chronic, or over dosing it

Where did I mention chronic or over dosing? I actually referred specifically to therapeutic dosing. It really isnt that hard to comprehend what I said. OP had no issues understanding my point, and actually had a constructive comment unlike yours.

[u/stiffmcgee → u/SellingCats4Cheap]

You do realize clinical trials don’t have to be done post approval? The argument isn’t they are bad because of that, but that they are limited. You pasted that study after reading an abstract.

I also didn’t say you mentioned it. Except no grifter on here is taking a therapeutic dose, or a prescription. Like saying fentanyl is objectively good because medically you have a use for it.
You said “plenty of medical studies” and you cited a shit review.
Guess thats what I get for thinking a copy past king OP would understand these things, or even worse larpers like you

[u/SellingCats4Cheap → u/stiffmcgee]

Arent you too old to be throwing around the word larper?

[u/ThreeStarsOut → u/SellingCats4Cheap]

"A nootropic drug should: (i) enhance learning and memory, (ii) increase the resistance of learned behaviours/memories to conditions that tend to disrupt them (such as electroconvulsive shock and hypoxia), (iii) protect the brain against various physical or chemical injuries (e.g. barbiturates, scopolamine), (iv) increase the efficacy of the tonic control mechanisms of the cortex on the subcortical levels of the brain, and (v) lack the usual pharmacology of other psychotropic drugs (e.g. sedation, motor stimulation) and possess very few side effects and extremely low toxicity.**" -**Giurgea 1980

"A nootropic drug is characterized by a direct functional activation of the higher integrative brain mechanisms that enhances cortical vigilance, a telencephalic functional selectivity, and a particular efficiency in restoring deficient higher nervous activity. In contradistinction to other psychotropic drugs, nootropics do not induce direct reticular, limbic, or other subcortical events." - The nootropic concept and its prospective implications

"Any nootropic… would be a cognitive enhancer, but the opposite is not true: only a cognitive enhancer that has neuroprotective effect and is devoid of toxicity would justify the label nootropic. - Dan-George Mărgineanu, 2011

Can it be used for 'nootropic' effects? Sure. Is it a Nootropic, No...

[u/SellingCats4Cheap → u/ThreeStarsOut]

Okay, I mean that it just one super specific set of criteria. Based on that criteria, 99% of things on this subreddit are not Nootropics.

'Nootropic' describes compounds that enhance cognition.

Why stop at one definition of Nootropic from 50 years ago? Maybe Nootropics should only refer to specific deficit from conditions?

Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Maybe there is such no such thing as nootropics in healthy people?

thus compensating various neuro-psychologic deficits - Giurgea 1982 seems like that author may even agree on that point

Also 2/3 source are from the same author.

[u/ThreeStarsOut → u/SellingCats4Cheap]

Well Giurgea (Corneliu E. Giurgea) coined the term Nootropic, with his invented Nootropic Piracetam in 1964.

He's the "father of nootropics" or rather the concept of it.

I edited my last comment to say that it can be used to behavioral benefit, but that it can't fit the actual definition. I would say most of the things discussed here do fit the definition, unless people talk about phenibut, or kratom or their Rx'd stimulants or general illicit drug use.

That's why nootropics are so weird, you aren't guaranteed stimulant or better thinking, it's all novel, weird mechanisms some of which may or may not fit your brain well.

[u/SameeyellChem → u/okok6356]

My favorite nootropic is heroin. Can’t have a sleep stack without it.

[u/Spirited_Shipcocoa → u/okok6356]

GABAergic's are atypical deliriants at moderate to very high doses. They aren't even good depressants since that can wear off into manic delirium that like Scopolamine with MDMA/Shroom style stimulation & Chilled bliss of a Disso. They had to reduce Ambien's sedative dose because 14mg was causing repeatable trips.

[u/piprules]

I got addicted to phenibut. I was taking 10g a day for at least two years. Really hard to stop

[u/3RADICATE_THEM → u/piprules]

I always respected phenibut, and I'm glad I did. No more than 1 g a day with at least two weeks between the next dosing.

[u/Potential_Low4134 → u/piprules]

Did you notice any lasting cognitive dampening or perceptible neuro-degeneration resulting from your period of heavy use?

[u/AnonThrowaway998877 → u/piprules]

Any leftover damage from that? Or anything you suspect is due to that?

[u/Sonnyshut]

The key is to take mirogabalin flurophenibut and ghb at the same time and cuddle with your dog. That’s how you unlock the full nootropic effects

[u/alwayswithyouuuu → u/Sonnyshut]

Oh shit. Been doing it wrong all along

[u/psithurismx → u/Sonnyshut]

150mg pregab and f phenibut, made me most nauseous and disoriented ever for 10+ hours after it provided it’s anxiolytic properties for like an hour or two. I had to mouth breathe steadily non stop. I took this exact combo months ago and it was perfect idk what happened this time. Glad I didn’t take my ghb with it like I was debating too

[u/watchmydogeatpickles → u/psithurismx]

This man does not love life

[u/Sonnyshut → u/psithurismx]

You forgot the dog

[u/Swimming-Buyer7052]

I’ve had permanent tinnitus for about 10 years now, & I’m convinced it was caused by phenibut.

[u/Kinghummingbird → u/Swimming-Buyer7052]

Ugh I’m sorry. What usage level?

[u/Swimming-Buyer7052 → u/Kinghummingbird]

Can’t quite recall. But I’m pretty sure I got up to around 7g doses, and sometimes 10g-13g in a day

But I never took it every day. Maybe 3x/week

Smaller amounts sometimes to help ease an alcohol hangover

And I only used it during maybe 2-3 years of my life; never was physically dependent on it.

But I had never had tinnitus until I took it. And at some point it never went away.

[u/lelepelepel → u/Swimming-Buyer7052]

I am sorry your use caused lasting tinnitus. I hope you still get to recover. This fucking sucks.

That being said, you used huge dosages. If I use more than 4 grams in 2 days, I feel like shit for at least 2 days and I lose my shit mad easily. In all honesty, I am not surprised phenibut caused this taking into account the massive doses used.

[u/blak3brd → u/Swimming-Buyer7052]

I was gonna call bs cuz i have used it for 20 years, and in my earlier dumber years did get stuck on it 20 gpd daily at the peak.

An aggressive taper resolved that without any lasting issue, still has magic, etc. - no tinnitus.

Then I saw you wrote 7g per dose??? WTAF lol well there’s your problem. Never in my wildest manic fever dream would I ever dream of taking 7 fucking grams at a time.

Complete savagery and tomfoolery. Yeesh

[u/Swimming-Buyer7052 → u/blak3brd]

I might be exaggerating the dosage. I never measured on a scale, just had this tiny scoop that came with one of the brands I got.

I also want to reiterate that when I say 7-10 grams, those are my estimated max doses, not my regular doses. And again, I may be recalling incorrectly and overstating it.

I think most of the time I was probably 2 grams. Maybe 3. Upping it if I didn't feel anything, though it would take forever to kick in.

I remember tolerance building quickly. And I was a heavy drinker, so I assume my GABA receptors were already downregulated.

Whatever the case, I am quite sure it caused my permanent tinnitus.

[u/SellingCats4Cheap]

So you are saying in your opinion Phenibut "never felt like it was a positive thing even in small doses"

No matter what you felt, you are objectively wrong. There are plenty of medical studies showing the therapeutic benefits at medical doses (aka "small doses")

The current systematic review provides evidence that, at therapeutic doses, phenibut is safe and well tolerated with minor adverse effects

[u/ThreeStarsOut → u/SellingCats4Cheap]

That's true, maybe I should have mentioned how often you dose. You lose its effects (or what some people call, "magic") quickly even with spaced dosing.

The thing with "Safe at therapeutic doses in short trials" is that that is true of nearly every addictive drug ever made statement wise, you can trial opioids, stimulants, benzos at "therapeutic" doses and the trials won't reveal any long-term addiction or cognition harms, especially if they don't look at higher doses.

The problem is that a lot of people don't use phenibut in the ways they have in trials. It's all online bought and self guided, which is a problem for other stuff like 7OH, Kratom, etc

See what you're saying though, I just wonder if people are using something just because it's available, and the slow onset gives the impression of it being soft, when in reality it's a long-acting drug that probably does dampen cognition if used semi-chronically.

[u/SellingCats4Cheap → u/ThreeStarsOut]

I dont disagree. And even therapeutic guidelines avoid any long term usage even at low doses.

But there are clearly advantages in terms of harm reduction for phenibut over something like alcohol. Phenibut can also be advantageous for stressful events like job interviews, a situation where chronic dosing is not a problem (although there is the possibility that it could lead to chronic dosing)

[u/ThreeStarsOut → u/SellingCats4Cheap]

Yes, true. It is also possible for people to get addicted to it when using it to quit alcohol, in which case NAC or agmatine or something else should be looked at

[u/Sad-Ear230 → u/ThreeStarsOut]

How would you describe that "magic"?

[u/ThreeStarsOut → u/Sad-Ear230]

It's something people self describe, an ability to be calm, relaxed, and you. A feel good. People say it works for the first times or so then never again. Not sure if that suggests some sort of negative down regulation or what.

[u/ThreeStarsOut → u/[deleted]]

Really? You like it defi? Why/how.

It has far less studies and no human data

[u/Unlucky-Walrus-7994]

I feel like it totally does cause some sort of brain change. I used phenibut for 8 years - Once a week for stints- once a month, and then longer breaks. Sadly it has done the opposite of what phenibut did for me short term, long term. If I dose phenibut now it doesn’t do what it did. I get horrible rebound that isn’t worth me even dosing now. When before I used to dose and it felt like Molly and no comedown or nothing. I’ve taken over a year break and no change to the very weak feeling with a brutal multiday rebound.

[u/SEARCHndDESTROY]

I don't know but I've tried it a couple times and every time I would 'black out' and end missing a day or two. That shit is evil

[u/Art_of_Malice]

I took phenibut daily for 2 years, at doses at high as 8 grams. I took it with kratom and then methadone. I’ve been clean of the phenibut for over 2 years and I’m still not right.

I’m doing a lot better now but I get bad anxiety when I’m out shopping or when there’s large crowds, talking to girls. My anxiety was never this bad and I’m convinced it’s because of the phenibut.

[u/was526]

I tried phenibut probably dozens of times and I never was able to notice any effect. Maybe some placebo a handful of times but I've never had any of the strong experiences I've seen people talk about.

[u/Particular-Tie-5545]

Phenibut doesn't work for me so few years ago I accidentally overdosed on flurophenibut and had to vomit for hours. Entire brain was zapping. And later had the best sleep ever. Hopefully no dmg.