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Phenibut 101

Phenibut is central nervous system depressant first synthesized by Professor Vsevolod Perekalin at the USSR Academy of Medical Sciences in the 1950s. First introduced into clinical use in the 1960s, Phenibut has enjoyed a long history of use over the past 60 years making it one of the oldest developed nootropics. In its early days, it was sent into space with cosmonauts to deal with the anxiety of space flight without affecting their ability to operate machinery. It is prescribed for the treatment of anxiety and insomnia, among other ailments, in Russia, Ukraine, Kazakhstan, and Latvia as the pharmaceutical Noofen.

The chemical structure of Phenibut

Is Phenibut Legal?

The answer to that question depends on where you live. While used for medical purposes in Russo-European countries, in the western world the drug is not approved to treat any ailments. However, Phenibut is not scheduled and is freely available in all countries with the exception of Australia. In February 2018, the Therapeutic Goods Administration of Australia listed Phenibut as a Prohibited Substance, criminalizing possession, use, sale or manufacture of the drug within Australian borders. For now, Phenibut remains freely available and easily found in the rest of the world.

What are the effects of Phenibut?

Phenibut’s effects include anxiolysis, hypnosis, nausea reduction, reduction of tics and stuttering, as well as general feelings of well-being. A recent study that looked at Phenibut in relation to ADHD found Phenibut, at a dose of 500 mg daily, improved anxiety and impassivity in teenagers that suffered from the ailment with a 63% success ratei. A 2014 study found that at 1000 mg a day, Phenibut improved attention, memory, and emotional intelligence in almost 3 out of every 4 patients that suffered from social anxietyii. Phenibut might turn out to be a better treatment for social anxiety due to its lower potential for abuse than traditional anti-anxiety medications such as Xanax, as well as its relatively benign profile of physical side effects.

Members of nootropic communities on sites like Reddit often attribute other effects to Phenibut such as claiming that it has stimulating, anti-depressant, or pro-cognitive effects. While these are theoretically possible, there is little to no clinical evidence that these are the results that a healthy individual can expect when taking Phenibut. That being said, recent studies have found Phenibut to be a possible treatment for improved attention in those suffering from social anxiety (as mentioned above). One hypothesis to explain this effect is that when someone suffering from social anxiety has that anxiety relieved they are less distracted by their ailment and able to put more attention towards cognitive tasks.

How does Phenibut work?

Phenibut is a GABAergic drug, meaning that it works on the GABA receptors in the brain. GABA receptors are the primary inhibitory receptors of the brain and function by opening a channel that allows chloride ions that carry a negative charge into the cell or positively charged potassium ions out of the cell depending on the what type of GABA receptor it is. Either way, the net effect is the same: the receptor activation causes the neuron to become more negatively charged in relation to its surroundings, a state known as hyperpolarization. This makes it less likely the neuron will fire in the case of an incoming signal from a connecting neuron.

When looking at the structures of the neurotransmitter GABA and Phenibut side by side it is easy to see the similarity in their structure. The only difference is the addition of a phenyl group on the β carbon. This is how Phenibut gets its name: β-Phenyl-γ-aminobutyric acid.

There are two primary GABA receptors GABAand GABAB. Phenibut works almost exclusively by agonizing the GABAreceptor, with GABAactivity only becoming apparent during very high doses. While there aren’t hard and fast rules that differentiate the effects of the two receptors on the human level, something can be gleaned from the fact that agonists (activators) of GABAA include Xanax, Klonopin, and Ethanol.

What type of Phenibut should I buy?

Phenibut is available in several different forms. In this section, we will go through a few of the available versions of Phenibut and list their positives and negatives.

Phenibut HCl

This is the gold-standard of Phenibut. For much of its history, this is the form that has been in the widest use and most readily available. It is very water soluble, orally bio-available, and has a consistent dosing pattern. Almost all of the dosages you read online or in scholarly articles are using the HCl salt. The only downside has to do with its acidity. If your stomach is easily upset, the acidity of Phenibut HCl may cause you to feel sick under certain circumstances. Drinking a glass of water with Phenibut HCl is unpleasant due to its intensely acidic taste.

Phenibut FAA

This is the free amino acid version of Phenibut. It has a neutral pH making it much easier to ingest by methods other than oral, as it can come into direct contact with mucous membranes without discomfort. This allows one to do sublingual dosing. This a very cost-effective version of Phenibut, since potency is increased by about three times, when taken sublingually, according to anecdotal reports on sites like Reddit. To add to this, it is also 15% more potent than the HCl salt when consumed orally. However, anecdotal reports claim Phenibut FAA has a slower onset when taken orally when compared to the HCl salt.

Phenibut XT

Phenibut XT is a popular preparation of Phenibut that is simply Phenibut HCl with filler in 500 mg capsules. The main advantage is easy dosing. The downside is the lack of ability to titrate your dose. You will also pay a premium for the convenience of buying a pill form.

F-Phenibut

Also known as Fluorophenibut, Fluorobut, and 4F-Phenibut. Unlike the other forms of Phenibut this is actually an entirely different molecule, having the addition of a Fluorine atom in the 4th position of the phenyl ring on Phenibut. Like Phenibut it is highly selective for the GABAreceptor over the GABAreceptor, however, based on anecdotal reporting the potency seems to be increased by an order of magnitude over Phenibut. Because of the relative newness of this chemical it still remains to be seen how safe it is with moderate use. Currently, it seems to share a similar risk profile as Phenibut itself. Most users report that the two molecules are almost indistinguishable in effect, and only requiring different dosages.

Things to consider when buying Phenibut

When buying Phenibut make sure that you are buying the product from a trustworthy source that has their products tested and has that testing available for review. When dealing with white powders you can never be too careful making sure you are getting the correct substance. Additionally, a scale is required to dose the compound, although a scale with a resolution of 0.1 grams is enough for this compound.

Finally, for all the good this supplement can do it does have the ability to be abused. While not as addictive as other GABA agonists, it still carries a moderate risk of addiction that should not be taken lightly. To add to this tolerance develops with regular use very quickly and for that reason it is recommended that research subjects only dose one to two times a week, ideally leaving several days in between.

Feel free to head over to our store to see the types of Phenibut we have in stock!

 


i Chutko LS, Surushkina EY, Yakovenko EA, Kroptov YD, Anisimova TI, Sergeev AV (2016). “Impulsivity in adolescents with attention deficit hyperactivity disorder”. Zh Nevrol Psikhiatr Im S S korsakova

ii Chutko LS, Surshkina Slu, Iakovenko EA, Nikishena IS, Anisimova TI, Bondarchuk Iul (2014). “Cognitive and emotional impairments in patients with protracted anxiety-phobic disorders”. Ter Arkh

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How can a substance have a purity over 100 percent??

At Supplements for Work, we strive to bring our customers the highest purity compounds possible. This means that all our compounds are tested to ensure that they behave in the way we would expect the compound to behave and are pure. We employ a third party chemical testing organization to ensure that the data we receive is accurate and truthful. Below is an example of one of those reports for a batch of Tianeptine Sodium.

A COA that we received from a third-party testing company.

Notice anything odd about the results? According to this analysis, our Tianeptine Sodium is 101.7% pure, which, while flattering, is physically impossible. I will attempt to explain how this result came to be and what our customers should take away from a Certificate Of Analysis (COA) like this.

To understand how it is possible to have an analytical purity above 100%, we first must understand how the purity is determined. In this case, High-Performance Liquid Chromatography (HPLC) is used. HPLC is a technique used to separate, identify, and quantify all the components of any given mixture. Most modern HPLC procedures use an all-in-one, self-contained machine.

Courtesy of www.Idex-hs.com
A diagram showing all the individual parts of an HPLC machine.

The basic set up of an HPLC is as follows: There are two reservoirs of solvents, one polar and one non-polar. These are mixed in different amounts over the 30-minute runtime. For example, a procedure might start out being 100% solvent A and slowly transition to being 100% solvent B after 25 minutes. The middle contains every variation in between those two extremes. This creates a gradient that pulls different compounds within a sample at different rates depending on how they interact with each solvent. These flow at very high pressure to a specialized analytical column designed to retain compounds within the column, creating a greater separation between the multiple compounds within a given sample.  On the other end of the column is a detector that scans the liquid that leaves the column. The detector is connected to a computer that compiles the data and outputs a graph like the one below.

An example of what an HPLC output looks like. Note that this HPLC protocol could be further improved to provide greater separation between the two tallest peaks.

The Y-axis represents the intensity of the signal the detector picked up (corresponding to concentration) while the X-axis shows the time that the compound left the column (corresponding to polarity).

To use this data to find out the purity of a substance you need to have a sample standard. This is a virtually pure sample of the compound that can be used to judge other samples against. Making something this pure is incredibly difficult and requires time-intensive work, so standards are notoriously expensive. For example, 5mg of Tianeptine Sodium Salt standard from Millipore Sigma is $254, and that is still only 98% pure.

The sample standard is dissolved at a known concentration (1 mg/ml) and run using the method that the experimental sample will be run at. The experimental sample is then dissolved at the same concentration (1 mg/ml) and run. An example of how this might look is below.

An example of a comparison between a pure reference standard and an impure compound.

By calculating the area under each peak and dividing the experimental peak by the standard peak we can find the purity of our compound. So how then can we get values greater than 100%? When dealing with weight values as low as 1 mg the accuracy of our equipment begins to break down, so it is possible when weighing out the 1 mg there was error intrinsic to the sample. For example, if 0.98 mg was weighed out instead of 1 mg/ml and our experimental sample was overweighed to 1.01 mg the sample would appear to be 103% pure. To combat this, liquid dilutions are sometimes used to spread the error over much more solution resulting in a lower error in the end results. However, this can be a problem when the material is prohibitively expensive as is the case with Tianeptine standards.

Even if the initial solution is a perfect 1.0000 mg/ml the equipment that samples the solution is not immune to malfunctioning and may take 19.99 μL instead to the programmed 20 μL, which can create a similar error as detailed above. This type of equipment malfunction can be caused by static electricity, miscalibration, or power surges.

The discrepancy can also be explained by an old standard solution of Tianeptine. Standard solutions are usually made very shortly in advance of the testing and are stored at -20 C or lower. If the solution is made too far in advance, or not stored properly in the run-up to the tests, then small amounts of compound degradation can occur. Then when this is compared to the other samples, it will make it appear to be a higher purity. This form of error can appear even with no fault of the chemist, as some compounds are just inherently unstable in solution and will begin to break apart almost immediately until an equilibrium of broken and unbroken molecules is reached.

Analytical chemistry is a complex field that requires immense precision on a level that most people are not used to thinking about. Experimental error is a part of the everyday reality of dealing with highly specialized and finicky equipment such as milligram balances, HPLC samplers, and HPLC columns. For the most part analytical chemistry succeeds in providing highly accurate information about compounds identity and purity, however, this is an uphill battle against the ever-present invasion of error into the scientific process. All we can do is try to minimize this error to the greatest extent possible and live with results knowing they are as close to the truth as we are able to get at this point.