stan08,
Thank you for the feedback, and the overview of your dosing plan. With that daily dosage, you likely will not run into any seriously noteworthy problems. The issue arises when users take higher and higher doses, to try and chase the slight dopamine-influx-mediating effect. Everybody is different as far as time-frame, but eventually you will notice the dopinergic effects of your normal dose, drop off a bit. However, for most people (including myself) that I have surveyed for clinical logistical evaluations, still retain relatively prominent anti-anxiety effects from their effective therapeutic dose. This is why it is important to start at the lowest effective dose, and work your way up only as you need to.
toto75015,
Your bring up a perfectly valid point, that I tried to touch on, in my previous posts. Using Phenibut "just for the hell of it" is rather pointless, as any dopamine-mediated mood-lift that you may get from it is minuscule, and is the first effect to diminish over long-term dosing. Although, for people with legitimate anxiety issues who do not have access to, or do not want to use, benzodiazepine drugs, Phenibut is a wonderful nootropic that happens to be out there for legitimate anxiety sufferers, as long as it is taken as-needed and responsibly, and is not discontinued too abruptly.
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.
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).
Kabb,
For the most part, you are absolutely correct; any long-term GABA site excitation followed by an abrupt discontinuance of the use of said agonist, can lead to dramatic imbalances in the Voltage-Gated Ca+ channels in the GABAergic neurons. Phenibut withdrawal follows many of the same symptoms of Benzodiazepine Withdrawal Syndrome, and withdrawal from other GABA -A Receptor agonists, like barbiturates, meprobamate, methaqualone, zolpidem, etc. Phenibut and several medically-used GABA -A agonists can roughly be considered “cross-tolerant“, but not directly because of their agonist effect at their respective target receptor subtype, but because the a2o calcium channel neurotransmission can become unbalanced in all GABAergic neurons if either Phenibut or a GABA -A agonist are used for an extended period of time, and both Phenibut and GABA -A Receptor agonists can help agonize those (now down-regulated) binding sites which helps to restore that Ca+ transmission within GABAergic neurons. So, yes, both Phenibut and benzodiazepines can suppress many of the symptoms of the other’s withdrawal syndrome, but not directly by working at the same binding sites.
I can assure you that Phenibut has less affinity for both the allosteric and GABA binding sites, as well as the Benzodiazepine Binding Sites on the GABA -A Receptor than endogenous GABA does itself. The Phenibut (and related compound) binding affinity profiles that we conducted almost perfectly backed up the previous publications out there (check the more recent Russian studies), that noted a very weak affinity for GABA -A Receptors that comprised of approximately only 0.002% of the total orally-absorbed dose of Phenibut that crosses the Blood-Brain-Barrier, and that out of what did bind, had an almost non-existent agonist action. (I believe the 2008 Dambrova et al paper measured it’s agonist strength at GABA -A Receptors at less than a 600,000th that of it’s agonistic strength at GABA -B Receptors). The addition of the cyclic phenyl ring on the GABA molecule that forms Phenibut, makes the drug highly selective for the GABA -B Receptors, and despite both functioning as binding sites for GABA (therefore allowing the neuro-transmission of similar Volgate-Gated Calcium channels), the ionotropic GABA -A Receptors and the metabotropic GABA -B Receptors are indeed very different receptor types, morphologically.
So, although yes, technically Phenibut does possess some very slight affinity for GABA -A Receptors, it is so minuscule that it is medically insignificant, and does not contribute to the pharmacological action that we associate with Phenibut, nor it’s withdrawal syndrome. (Remember, that another large portion of Phenibut’s anxiolytic action is also due to it’s a2o Ca+ channel modulation (as a gabapentinoid) in GABAergic neurons, with is an action that neither benzodiazepines or Baclofen possess).
The main difference between the withdrawal syndrome associated with Phenibut and strong GABA -A Receptor agonists, like benzodiazepines and barbiturates, is that although severe Phenibut withdrawal may make you feel like hell, it’s typically not a medical emergency the way that withdrawal from the ionotropic GABA -A or GHB Receptors can be, in the sense of causing Grand Mal, Myoclonic, and Absence seizures - as well high hypertension and severe cardiac arrhythmia often do. (Unless you are a preexisting epileptic, have an acetylcholine imbalance, or are taking medications that lower the seizure threshold, such as something like quetiapine, for example). As long as you do not suffer a preexisting cardiac, epileptic, severe hypertensive disorder, or take any medications that may be contraindicated when withdrawing from an excessive dose of Phenibut, you are not medically at risk the same way that you can quickly become, by abruptly withdrawing from long-term use of a strong ionotropic GABA -A Receptor agonist, like a benzodiazepine.
However, although there may not be any noteworthy cross-reactivity at their binding sites, the effects on Ca+ channel transmission in GABAergic neurons is similar, and their pharmacological effects on our mood and behavior can be similar. This is what myself and medievil were discussing about using a benzodiazepine for a week or two when stopping long-term Phenibut use, in the small percentage that experience extreme rebound anxiety, even when gradually withdrawing their therapeutic Phenibut dose. The idea behind this is that although the neurotransmission at the now down-regulated GABA -B Receptors will still be unbalanced, and technically those sites will still be in the withdrawal state, the use of a GABA -A agonist benzodiazepine will suppress pretty much every symptom of the GABA -B Receptor withdrawal, plus the additional rebound anxiety that some experience, and will keep the individual comfortable during the time that it takes for the GABA -B Receptors to up-regulate again, to the state that they were before the use of Phenibut. (Again though, many individuals do get a bit too comfortable with benzodiazepines, and if you are the type of individual that gets yourself into trouble with a simple amino acid (Phenibut), than you can potentially get yourself into even greater trouble with benzos if you overuse them. So, I recommend the use of a benzodiazepine to withdraw only if you are part of the small percentage of people with a true, severe anxiety disorder, that experiences unbearable rebound anxiety, even when gradually weaning down your dose).
I still have to stand by both my personal experience, pharmacological experimentation, and clinical evaluation of volunteer participants, that Phenibut (for a very large majority, at least) can absolutely be discontinued by gradually reducing the dose. (For those participants that we studied, which were diagnosed with either Situational Anxiety Disorder or Panic Attack Disorder, the full therapeutic dosage (500mg - 2000mg) was discontinued by 10% over ten weeks time, with no significant withdrawal symptoms noted. And, in the event that any users out there DO feel any withdrawal discomfort or rebound anxiety, simply keep the dose where it’s at, and wean slower. However, in my experience, many users without significant or legitimate anxiety disorders can wean at least that quickly, and even more rapidly in many cases. The idea is, that by stretching your dose reduction over a ten-week period, you allow time for your GABA -B Receptors the necessary time to up-regulate to their previous sensitivity, before you started taking Phenibut. I have no doubt that people do run into trouble with Phenibut (we‘ve all seen the posts), but if the dose is weaned correctly and gradually enough, you absolutely can avoid withdrawal syndrome, like with just about any psychoactive drug (even many more serious drugs in the case of physical dependency and addiction, like opioids, cocaine, amphetamines, etc). It is absolutely shocking to me how many people seem to get in trouble with, and become horribly dependent to a simple phenylated version of an endogenous amino acid. (Of course, GHB addiction is just that, but GABA -B agonists are rather benign, and can be effectively weaned).
One think that I want to clear up, since some of the posters in this thread seem to think that I am actively promoting the use of Phenibut for everybody, is that Phenibut IS a drug. Many people in the nootropic circles like to think of Phenibut as a dietary supplement, the same way that tyrosine supplements are used. Although Phenibut is based off of one of our endogenous neurotransmitters (GABA), it IS mad-made, does not occur naturally in nature such as a plant alkaloid or an endogenous protein, hormone, or neurotransmitter. - It is a man-made drug, and should be treated as such. As somebody who suffers from a legitimate anxiety disorder and who uses Phenibut in conjunction with other medications, I absolutely believe that it should be accessible to people who would benefit from it and do not have other available treatment options (or who do not tolerate some prescription treatment avenues very well). However, I fully admit that like any psychiatric drug (particularly as a GABA agonist), that it should only be used by informed individuals who understand and know how to effectively mitigate any risks associated with it’s use (and it’s discontinuance). Using Phenibut in an attempt to feel good is not a problem if it is used legitimately and responsibly, but using Phenibut searching for a “high” or “pick-me-up” is just illogical - it doesn’t produce effects that most would consider “recreational” and you will eventually become tolerant and possibly dependent on it if used habitually.
Probably the biggest problem with Phenibut use, as far as these internet horror stories go, is that people will look up a random supplier and order a given amount of Phenibut. Many times the doses are not even weighed accurately, and are just sort of eye-balled. Furthermore, who have tons of conflicting data online about what the correct dosage range is, and the risks of long-term administration, with very little (and conflicting) data on how to effectively stop using phenibut when the patient wishes to. Since Phenibut is often lumped into the nootropic drug categories (alongside things like Piracetam and choline supplements), people seem to assume that they can just order some, be very flexible in their dosage, use it until they no longer feel much from it, and then simply stop using it. Well, you can do that with most nootropic drugs and supplements without any legitimate withdrawal effects, but a lot of users (and suppliers) are not making the correct distinctions between using drugs like Piracetam and supplements like Tyrosine, with a GABA -B agonist, like Phenibut. So, people (usually at the recommendation of the supplier or others, online) order their own supply, use it rather sporadically and haphazardly, and really have no logistical plan on how to discontinue their use, when that time comes. (Then they are surprised when they find out how accustomed their GABA Receptors have become to having it, and then write long, angry posts online, vilifying Phenibut as some terrible drug of addiction).
Let’s not forget that many categories of psychotropic drugs, even many used medically, in psychiatry and neurology, carry dependency liabilities - even in many categories of drugs with no abuse potential, such as many serotonergic drugs, other class antidepressants, mood stabilizing drugs, antipsychotic medications, ADD and ADHD drugs, sleep disorder medications, dementia and Alzheimer’s drugs, some cognitive-enhancing drugs, etc., all can cause fairly extreme side-effects, but many can also cause fairly serious withdrawal syndromes, if they are abruptly discontinued. Think even of some of the more commonly-used antidepressants, perhaps a drug like Mirtazepine (brand name Remeron, in the US). Despite being one of those drugs that psychiatrists love to hand out, if used in moderate - large doses, over an extended period of time, and then abruptly stopped, without weaning down the dose, Mirtazepine’s withdrawal syndrome can include severe anxiety, tremor, vertigo, restlessness, irritability, decreased appetite, insomnia, diarrhoea, nausea, flu-like symptoms, pruritus, cluster headaches and in some cases hypomania, mania, psychosis, and acetylcholine-deficient-caused convulsions. (I actually had friend who used to work with the biochemistry section of our team, who’s mother suffered a seizure upon discontinuing mirtazepine, who now has some degree of permanent facial paralysis). Mirtazepine is just one example of one of the classes of drugs that psychiatrists generally love to prescribe, that not only carry side-effect profiles that can be intense, but also withdrawal syndromes.
So, before vilifying Phenibut (which, as covered, is a simple phenylated version of an amino acid already found in our brains), just understand that it is a drug, and not a simple choline supplement or vitamin that can be taken or discontinued whenever the user feels like it. If you have a legitimate reason to try Phenibut, and you decide that you are going to use it - just understand that you will have to do so the same way that you would take any medically-administered psychiatric drug. (Meaning taking consistent doses, at consistent intervals, and following a pre-implemented dose-reduction schedule beforehand. That way, if/when you discontinue Phenibut use, you can reduce your dose gradually enough that your down-regulated GABA -B Receptors have some time to rebalance Ca+ neurotransmission, before you stop dosing all together. (It is also a good idea to let a physician or psychiatrist that you can see at least semi-regularly know what you are doing, so that they can evaluate your status, and pick up on things that you may have missed). I work alongside medical teams (usually on clinical evaluations for new psychotropic compounds, like our Phenagabine evaluation, due to be published next year) and I often review patient records, and am even in contact with many patients locally and via the internet (email, Skype, ect). It is always a good idea to have somebody with the right background reviewing your progress every so often, as sometimes when we self-diagnose, we see only what we want to, and we miss things that can turn out to be important in the long-run.
explr9 claims that I am providing “massive disinformation” and “marketing”. First of all, I have not claimed anything about the compounds mentioned in this thread, regarding their activity or use that has not been scientifically vetted (in many cases, I have done the work first-hand), and secondly, I certainly am not pushing Phenibut as some magical substance that everybody should use. As somebody who is intimately familiar with it’s pharmacology and clinical profile, as well as somebody who has benefited from it, and seen many others benefit from it, I absolutely believe Phenibut to be a valuable compound, and I believe that those who legitimately have the need for it, should have access to it. Do I think that it’s over-used? Yes, absolutely, there are many people using it simply to chase some kind of “high” or sedative, anxiolytic benzodiazepine-like effect from it, which it simply does not possess. Those individuals who genuinely have a need for it may feel much better after taking it, but it certainly is not a “legal high” or a drug that should be purchased with any big expectation of a recreational, euphoric effect.
It is, after-all, a man-made molecule, and by definition a drug (and not a dietary or nutritional supplement), and should be treated with some level of seriousness, and not used recklessly. By psychopharmacological standards, compared to many of our approved psychiatric medications today, it has a very good tolerability and safety profile in healthy individuals, and it also has very few clinically-relevant side-effects compared to many of the medications that are also approved to treat the conditions that Phenibut treats. It also has a low toxicity (LD50), and does not adversely interfere with many other pharmaceutical compounds. The only real drawback that it does have, is that by being a GABA -B agonist, it can cause some form of GABAergic mediated dependency. (Again, it’s hard for me to truly even classify Phenibut as being “addictive” in the psychological sense of the definition, since nobody really craves it’s effects, or actively seeks out it’s effects). Although, in comparison to almost all ionotropic GABA -A Receptor agonists, the withdrawal syndrome is less pronounced, less dangerous, and can be mitigated or eliminated altogether by a carefully-implemented taper plan, to gradually wean the dose down before stopping treatment outright.
This is basically what it all comes down to. This is the reason that some people have found it a life-saver, and have been on it for years (like myself), and why some people take it for two months, run out, and then suffer ugly withdrawals, and curse it as a poison. It is also really important to note that everybody’s biochemistry and neuro-morphology is varyingly different. The only way to know how you will respond personally, is to begin treatment yourself (low doses initially), and adjust your treatment based on your response. Kabb mentioned that I may be in the “honeymoon phase” with the benzodiazepine drugs that I use to control anxiety. Though, in all reality, I have always been able to use both very large doses, and a very numerous number of GABAergic drugs with no significant dependency issue. My tolerance develops fast, but I do not suffer the withdrawal syndrome that most people do. So, it really does come down to personal neurochemistry and psychology as far as what works for one person, and what works for another. There’s really not much else that can be said on the Phenibut issue. - It can be extremely useful for many people, though it still can cause an unpleasant withdrawal syndrome if discontinued too quickly. It’s not a “good” or “bad” drug, either way, it’s simply a drug. All we can do is educate those who do use it, with the best medical data and personal experience that we can. (Which was the main reason I decided to join Longecity, or to participate in this field at all.. - to learn all that we can, and disseminate that knowledge to other people, so they can make informed decisions).
Phenibut will surely have an effect if you take a high enough dose. As far as I know, Phenibut is not a nootropic and drugs which increase the activity of GABA receptors (either A or B) tend to have a marked adverse effects on memory which may qualify them to be opposite of a nootropic.
If you wish to post about your daily dosing with Phenibut (or alcohol, baclofen, barbiturates) then I wonder if you might find a more receptive audience in a forum discussing recreational drugs?
The only people I can think for whom a GABA-ergic drug like Phenibut might help with their cognition are those whose function is badly impaired by excessive anxiety and they can often be found exchanging information on anxiolytic drugs and other coping strategies on mental health forums.
Sorry to sound like a party pooper. 
Kabb made a good point, here. Although technically not a nootropic drug (since it has no effect of cognition or memory-enhacement), it is often lumped into the nootropic category, and sold by as lot of the same types of suppliers. Echoing what I said in my above post, Phenibut really only has a noteworthy benefit, or significant improvement on mood in those who actually have legitimate anxiety disorders, and who naturally have GABA (/norepinephrine/glutamate) deficiencies. In my experience, a lot of the people who wind up posting those horrible withdrawal stories, are generally indidivudals that didn't really need to use Phenibut in the first-place, and were careless and reckless with their dosing, since upon initial encounter, Phenibut's effects are pretty subtle (compared to many other man-made psychotropic drugs, at least). This is the biggest point that I think people should take away from this thread.
If you wish to post about your daily dosing with Phenibut (or alcohol, baclofen, barbiturates) then I wonder if you might find a more receptive audience in a forum discussing recreational drugs?
The only people I can think for whom a GABA-ergic drug like Phenibut might help with their cognition are those whose function is badly impaired by excessive anxiety and they can often be found exchanging information on anxiolytic drugs and other coping strategies on mental health forums.
Sorry to sound like a party pooper.
Personally, I would be interested in how Sarif responds, after all of this discussion. Also, although technically not a nootropic drug, Phenibut is certainly psychotropic, and I may be a new member here, but I certainly feel that it's discussion has a place on a forum like this one. It seems to me that a lot of the membership here are focused on the technological advances that will allow humans to live as long as possible. - Well, I feel that the biggest part of that is how we feel during the course of our lives, and any potentially therapeutic compounds, certainly have a place in the discussions here, in my opinion. Just look at some of the current work by the teams at John Hopkins Medical School and The University of Hannover in Germany, in investigated prescription applications for Methylenedioxymethamphetamine (MDMA, or by the street name "Ecstasy"). A lot of the studies into MDMA for anxiety disorders and things like Post-Traumatic Stress Disorder that were shut down during the 1960's are now resurfacing, with the first in-vivo human trials in 30+ years. Exciting stuff!
Sarif, I see that you've sent me a private message. If you want, we can coordinate your treatment either through this site, email, Skype, etc., so that you have somebody educated monitoring your response to treatment. This basically just consists of a lot of general questions into how you're feeling, and how you're functioning. The most important questions initially are: *What kind of symptoms first made you consider using Phenibut? *What dose and what form (Free-Amino-Acid of hydrochloride salt) are you using? *What time of day are you dosing (morning or night), and how many times per day are you dosing (once, or twice, generally). *What are you taking besides Phenibut, and what are you eating and/or drinking around the time that you take your daily Phenibut dose(s)?
The answers to all of these questions can be forwarded to me via private message here, or preferably at Oracle.Laboratories@yahoo.com.
-J. Gona
Pysychopharmacologist,
Psychotropic Treatment Specialist
Oracle Laboratories,
NeuroPsych Institute
