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Phenibut
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    Overview

    Phenibut is a reference material that may have some nootropic, or cognition-enhancing, effects in research subjects. The key benefits it may offer according to scientific research in humans and animals are in the areas of cognitive enhancement (particularly memory, motivation, attention and self control), anxiety, sleep, and stress regulation.

    It’s an analogue — meaning it’s substantially similar in structure — of gamma-aminobutyric acid (GABA), a key inhibitory neurotransmitter that has calming and anxiolytic properties. It’s considered a GABA receptor  agonist, so it can fit in the receptor and activate it in a similar manner. For this reason, researchers are interested in its potential GABA-like actions [1].

    There are laws regulating phenibut as a prescription drug in some countries; in others, including in the United States, it is perfectly legal to possess.

    This guide reviews the potential applications of phenibut in research, along with potential side effects and some other important things to know about this reference material.

    Benefits

    The vast majority of research studies on phenibut have been done in animals, but we can use the findings from these to inform future research in humans. Here are some of the potential benefits of phenibut.

    One high-quality Russian study on phenibut noted that one month of treatment with 500-700 mg phenibut per day helped improve cognitive function in children with ADHD. Specifically, the phenibut group experienced improvements in self-control, attention, and memory compared to the control group [2].

    Another high quality Russian study — this one in adults — found that phenibut administration to people with chronic fatigue improved motivation and decreased mental fatigue compared to a control group that didn’t receive phenibut [3].

    Yet another human trial also showed that a combination of phenibut and ipidacrine (a Russian ACE inhibitor used for memory loss) improved attention, memory, speech, and psychomotor functioning in adults [4].

    Animal research shows that phenibut may offer some neuroprotective effects in subjects, helping to preserve cognitive function after physical trauma to the brain resulting from injury or blood flow insufficiency [5, 6].

    One study in rats also found that phenibut administration improved communication between the two hemispheres of the brain, which may help to explain its potential nootropic benefits [7].

    Phenibut is an anxiolytic, meaning it reduces anxiety. It does this by activating GABAB receptors, providing the same inhibitory effects as the neurotransmitter GABA.

    In Russia, it may be used as part of a treatment plan for anxious-phobic disorders in children and adults [8].

    In one chart review of 62 adult patients with anxiety or phobia disorders, researchers found that the use of 1000 mg/day of phenibut was associated with improvements in symptoms in nearly three-fourths of the cases [9].

    Because of these findings, in conjunction with animal research suggesting that phenibut may help regulate the body’s stress response (which we discuss further below), researchers are particularly interested in the potential effects of phenibut on reducing social anxiety in adult subjects—particularly in stressful situations.

    The downside is that it has a high addiction potential, and there are some case reports available of documented phenibut addiction [10, 11, 12].

    In countries where it is a prescription drug, phenibut is indicated for the management of insomnia.

    One study on Russian children found that phenibut reduced the symptoms of sleep disorders [13].

    However, some researchers caution against the use of phenibut for a sleep aid because of its high risk of dependency [10].

    One interesting finding that’s been noted in several animal studies is that phenibut appears to help regulate the stress response.

    Continuous activation of the sympathetic nervous system can lead to several issues, namely inflammation, immune dysfunction, and sleep issues.

    However, phenibut may help to reverse this sympathetic nervous system (“fight or flight”) overreactivity by helping to activate the parasympathetic nervous system, which signals a return to a normal, non-stressed state [14, 15, 16, 17,18, 19].

    Although all of this research has been done in animals, this stress-reduction potential is of particular interest to some researchers investigating social anxiety and stress in humans.

    Keep in mind, though, that some of these studies (unless mentioned otherwise) aren’t what we would consider high-quality scientific evidence — which comes from randomized controlled trials in humans. So, there’s no guarantee that phenibut will offer these same benefits in human research subjects.

    Additionally, the evidence we do have from high quality RCTs are mostly from studies done with adolescent subjects, so the findings aren’t necessarily applicable to adults. Although, again, they do offer a promising starting point.

    Side Effects

    Subjects can become dependent on or addicted to phenibut, resulting in withdrawal symptoms once it’s discontinued. It can also have intoxicating effects and result in mental status changes in the subject taking it. In a 2019 review in Current Psychiatry Reports, Edward Jouney described its effects as “similar to that of a prescription strength sedative [20].”

    In a 2020 review of several phenibut trials and case reports, researchers have also noted a few other side effects — some with the potential to be serious [1].

    In case reports in 16 patients, researchers noted that high doses of phenibut (0.5-100 grams/day) could affect the heart and potentially cause insomnia, anxiety, hallucinations and sedation. It’s important to note that many of these doses are substantially higher than the recommended dose of 0.25-2 grams/day, though.

    In 11 different clinical trials in over 580 patients, researchers noted side effects in about 6% of patients, and the most commonly reported side effect was drowsiness.

    Regardless, the U.S. Centers for Disease Control and Prevention (CDC) has identified one case where phenibut exposure (with no other substances or agents) resulted in death. No other details are available regarding the dose or circumstances of this death at this time [21].

    When conducting research, it’s important to keep in mind the addictive and intoxicating potential of phenibut at higher doses.

    Dosage

    In most studies, phenibut doses are calculated using milligrams of phenibut per kilogram of body weight.

    This holds true in human trials on phenibut too. However, these trials are few and far between, and all of them were done in Russia, where phenibut is available only as a prescription medication.

    Two of these trials that noted positive effects from phenibut administration, both in children, used dosages of 15-20 mg/kg per day, divided into 2 or 3 doses each day [2, 13].

    Another noted positive effects from 1,000 mg daily dose in adults [9].

    Some subjects note that phenibut may take up to 3 hours to fully take effect.

    Note that — because of the potential for dependence on phenibut — administration to research subjects should be minimal, preferably no more than two non-consecutive days per week.

    As with all compounds, studies should be performed using the lowest effective dose. At 15 mg/kg/day, this would be a dose of approximately 1,000 mg for a 70 kg (154 pound) individual divided into two 500 mg doses or three 330 mg doses daily.

    However, it may be prudent to start research subjects on even lower doses due to the risks associated with phenibut.

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    Legality

    At this time, phenibut is unregulated in the United States and most of Western Europe, including the United Kingdom. It is sold as a reference material that’s readily available for research purposes in these countries.

    Some companies have marketed phenibut-containing products as “dietary supplements” in the past, but the U.S. Food and Drug Administration released a memo in 2019 explaining that phenibut does not meet the criteria for a dietary ingredient. Any supplements containing phenibut are mislabeled, per the FDA’s guidance [22].

    In the U.S., phenibut is classified as an “Unapproved New Drug,” meaning that it is uncontrolled — with the exception that it can’t legally be included in dietary supplements, foods, or drugs.

    In Australia, it has been classified as a controlled substance due to its addictive properties and widespread recreational use. It’s also a controlled substance in France, Hungary, Italy, and Lithuania. There are talks of changing its classification to that of a controlled substance in some other European countries as well.

    However, it’s available as a prescription drug in many Eastern European countries — Russia, Ukraine, Belarus, Kazakhstan and Latvia, to be specific. Its brand names in these countries include Anvifen, Fenibut, and Noofen.

    Unlike some other potentially cognitive enhancing reference materials, phenibut is not currently banned by the World Anti-Doping Agency (WADA) for use in competitive athletes.

    Pharmacology

    Phenibut has a chemical name of beta-phenyl-gamma-aminobutyric acid and is sometimes called aminophenylbutyric acid. It is structurally similar to GABA, but with a phenyl ring at the beta position. As a GABA analogue, it exerts many of the same effects as GABA [23].

    Phenibut is well absorbed and able to cross the blood-brain barrier — thanks specifically to the presence of the phenyl ring. It has a half-life of approximately 5 hours and is excreted through the urine after being metabolized [24].

    Once administered, phenibut acts as a GABA receptor agonist. This means that it can activate GABA receptors in the same way that GABA itself can, leading to its characteristic calming effects. Other GABA analogues that are closely related to phenibut include:

    • Baclofen
    • 4-fluorophenibut
    • Tolibut
    • Pregabalin
    • Gabapentin
    • beta-hydroxy-GABA

    Phenibut may also increase dopamine levels in the brain, which may be why it possesses a euphoric effect [24].

    Clinical trials investigating how the chemical works have only been done on therapeutic doses, not recreational doses — which are much higher. Therefore, it’s not entirely clear how phenibut reacts in the body in extremely high doses.

    Phenibut HCL VS. Phenibut FAA

    Two of the available phenibut forms are phenibut hydrochloride (phenibut HCl) and phenibut free amino acid (FAA). These two forms each have their own pros and cons.

    Phenibut HCl is the most widely available form and the one primarily used in research studies. It is the hydrochloride salt form of phenibut, making it easily absorbable. It is a powder form that can be mixed into water or another beverage, or loaded into capsules for administration. Something to keep in mind, however, is that phenibut HCl has a bitter taste and is acidic due to the hydrochloride it contains.

    Alternative, phenibut FAA — as the name suggests — is the free phenibut molecule. While at first thought it may seem like a better option because it contains nothing “extra,” there are some drawbacks to phenibut FAA. While it is more pure than phenibut HCl, it doesn’t dissolve easily — so it’s not appropriate for mixing into a beverage or for loading into a capsule.

    The preferred way to administer phenibut FAA is sublingually (placing it under the tongue) until it dissolves. However, it also has a bitter taste and, unlike phenibut HCl, can’t be masked with a beverage since it must be administered sublingually.

    Generally, phenibut HCl is the more widely used and preferred of the two for research applications. It’s the form that has been used in nearly all clinical trials of phenibut, and the hydrochloride salt form has the benefit of being readily absorbable. It also dissolves easily in water, and is the less expensive of the two.

    A third form, F-phenibut or fluorophenibut, is also available. It’s slightly more potent than phenibut, however, it’s more difficult to source and more expensive.

    For general research purposes, phenibut HCl is more than sufficient. Regardless, phenibut FAA is available for researchers requiring a purer form of phenibut.

    Where to buy Phenibut Online

    Our preferred phenibut vendor is Science.bio. They offer both phenibut HCl and phenibut FAA powder, along with F-phenibut FAA and F-phenibut HCl. Here are the specific phenibut products and concentrations they offer:

    • F-phenibut FAA 10 g powder
    • F-phenibut HCl 10 g powder
    • Phenibut HCl 3000 mg solution
    • Phenibut HCl 50 g powder
    • Phenibut FAA 50 g powder

    However, the reason we like Science.bio goes far beyond their product offerings. They are a trusted provider of research and reference materials for scientific research in the emerging fields of nootropics and other life sciences.

    Their quality control practices are also rigorous, involving five key steps according to their website:

    • Sourcing of the highest quality materials from our suppliers
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    • Honesty and integrity in our marketing”

    They also complete the following tests on each and every batch of product utilizing both third-party labs and their own in-house testing:

    • High performance liquid chromatography
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    • Thermogravimetric analysis
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    • Fourier-transform infrared spectroscopy
    • Titration

    These tests verify the identity, purity and structure of each product, and ensure that the products are free of heavy metals and other contaminants.

    Additionally, Science.bio has excellent customer service. They provide free shipping on orders in the United States over $100, and world-wide shipping at reasonable costs. Most orders ship out on the same day, also.

    They also offer 10% off initial orders after signing up for their email newsletter.

    For these reasons, Science.bio is the only vendor we recommend for phenibut.

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    History

    Phenibut was first developed in the Soviet Union in the 1960s, where it was then introduced as a prescription drug for anxiety and insomnia. It’s a synthetic GABA receptor agonist. Currently, it’s available with a prescription in Russia, Ukraine, Belarus, Kazakhstan, and Latvia. In addition to anxiety and insomnia, its now used for several other indications in Russia, including:

    • Depression,
    • Alcoholism
    • Post-traumatic stress disorder
    • Meniere’s disease
    • Motion sickness prevention

    Most clinical research on phenibut has been done in Russia, while much of the research in Western countries has centered around phenibut addiction, withdrawal, and toxicity.

    PHENIBUT. JUST. WORKS.

    Phenibut is a synthetic GABA receptor agonist that offers anxiolytic and sleep promoting effects. Researchers are also interested in its potential nootropic effects, especially in regards to social anxiety and stress reduction; however, high quality trials in humans are lacking.

    Phenibut should be handled with caution due to its potential risks. Because of its sedative and brain-altering effects, it may have serious side effects and be potentially addictive at excessive doses. However, the most common side effect of phenibut is drowsiness.

    Human trials in phenibut utilize doses of 15-20 mg/kg body weight, divided into 2 or 3 doses daily.

    Its legality varies significantly across the world. Although it’s a prescription drug in some Eastern European countries like Russia, and a controlled substance in Australia, it is considered an Unapproved New Drug by the U.S. FDA and cannot be included in drugs, foods, or dietary supplements. While phenibut is legal to possess across the United States, it should only be handled by qualified professionals until we know more about its safety.

    The most commonly used, dependable, and inexpensive form of phenibut is phenibut HCl; however, phenibut FAA and F-phenibut are available as well. Thanks to their stringent quality control processes and excellent customer service, Science.bio is the only phenibut vendor we recommend.

    In closing, phenibut offers some promising potential as a nootropic agent. However, more high-quality human research is needed to fully understand the cognitive benefits it offers

    REFERENCES

    1. Kupats E, Vrublevska J, Zvejniece B, et al. Safety and Tolerability of the Anxiolytic and Nootropic Drug Phenibut: A Systematic Review of Clinical Trials and Case Reports. Pharmacopsychiatry. 2020;53(5):201-208. doi:10.1055/a-1151-5017
    2. Zavadenko NN, Suvorinova NIu. Zh Nevrol Psikhiatr Im S S Korsakova. 2014;114(9):19-24.
    3. Vorob'eva OV, Rusaya VV. Éffektivnost' i bezopasnost' preparata noofen v terapii sindroma khronicheskoĭ ustalosti u bol'nykh s tserebrovaskuliarnoĭ nedostatochnost'iu [Efficacy and safety of noophen in the treatment of chronic fatigue syndrome in patients with cerebrovascular insufficiency]. Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(11):31-36. doi:10.17116/jnevro201711711131-36
    4. Osovska NY, Knyazkova II, Kuzminova NV, Mazur YV, Shchepina NV. THERAPEUTIC APPROACHES TO THE CORRECTION OF COGNITIVE IMPAIRMENT IN PATIENTS WITH HYPERTENSION AND TYPE 2 DIABETES. Wiad Lek. 2020;73(11):2438-2442.
    5. Kupats E, Stelfa G, Zvejniece B, et al. Mitochondrial-Protective Effects of R-Phenibut after Experimental Traumatic Brain Injury. Oxid Med Cell Longev. 2020;2020:9364598. Published 2020 Nov 21. doi:10.1155/2020/9364598
    6. Vavers E, Zvejniece L, Svalbe B, et al. The neuroprotective effects of R-phenibut after focal cerebral ischemia. Pharmacol Res. 2016;113(Pt B):796-801. doi:10.1016/j.phrs.2015.11.013
    7. Borodkina LE, Molodavkin GM, Tiurenkov IN. Eksp Klin Farmakol. 2009;72(1):57-59.
    8. Chutko LS, Surushkina SY, Anisimova TI. Zh Nevrol Psikhiatr Im S S Korsakova. 2016;116(1):99-103. doi:10.17116/jnevro20161161199-103
    9. Chutko LS, Surushkina SIu, Iakovenko EA, Nikishena IS, Anisimova TI, Bondarchuk IuL. Ter Arkh. 2014;86(12):61-65. doi:10.17116/terarkh2014861261-65
    10. Samokhvalov AV, Paton-Gay CL, Balchand K, Rehm J. Phenibut dependence. BMJ Case Rep. 2013;2013:bcr2012008381. Published 2013 Feb 6. doi:10.1136/bcr-2012-008381
    11. Zheng KH, Khan A, Espiridion ED. Phenibut Addiction in a Patient with Substance Use Disorder. Cureus. 2019;11(7):e5230. Published 2019 Jul 24. doi:10.7759/cureus.5230
    12. Coenen NCB, Dijkstra BAG, Batalla A, Schellekens AFA. Detoxification of a Patient With Comorbid Dependence on Phenibut and Benzodiazepines by Tapering With Baclofen: Case Report. J Clin Psychopharmacol. 2019;39(5):511-514. doi:10.1097/JCP.0000000000001104
    13. Shypilova EM, Zavadenko NN, Nesterovskiy YE. Profilakticheskaia terapiia golovnoĭ boli napriazheniia u deteĭ i podrostkov [Preventive treatment of tension headache in children and adolescents]. Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(7):36-42. doi:10.17116/jnevro20171177136-42
    14. Samotrueva MA, Tiurenkov IN, Teplyĭ DL, Kuleshevskaia NR, Khlebtsova EV. Eksp Klin Farmakol. 2010;73(5):30-32.
    15. Ziablintseva EA. Zh Vyssh Nerv Deiat Im I P Pavlova. 2006;56(2):236-241.
    16. Kovalev GV, Spasov AA, Bogachev NA, Petrianik VD, Ostrovskiĭ OV. Rol' GAMK-ergicheskoĭ sistemy v mekhanizme stress-reguliruiushchego deĭstviia fenibuta [Role of the GABAergic system in the mechanism of the stress-regulating action of phenibut]. Biull Eksp Biol Med. 1987;104(11):588-590.
    17. Shul'gina GI, Petrishcheva AP, Kuznetsova GG. Vliianie proizvodnogo GAMK--fenibut na povedenie i aktivnost' neĭronov zritel'noĭ kory krolikov pri vyrabotke oboronitel'nogo refleksa i vnutrennego tormozheniia [Effect of a derivative of GABA, phenibut, on behavior and the activity of visual cortex neurons of the rabbit during elaboration of a defensive reflex and internal inhibition]. Zh Vyssh Nerv Deiat Im I P Pavlova. 1985;35(4):695-702.
    18. Ziablintseva EA, Pavlova IV. Ross Fiziol Zh Im I M Sechenova. 2009;95(9):907-918.
    19. Zyablitseva EA, Pavlova IV. Effects of the GABA receptor agonist phenibut on behavior and respiration in rabbits in emotionally negative situations. Neurosci Behav Physiol. 2008;38(6):555-562. doi:10.1007/s11055-008-9025-2
    20. Jouney EA. Phenibut (β-Phenyl-γ-Aminobutyric Acid): an Easily Obtainable "Dietary Supplement" With Propensities for Physical Dependence and Addiction. Curr Psychiatry Rep. 2019;21(4):23. Published 2019 Mar 9. doi:10.1007/s11920-019-1009-0
    21. Graves JM, Dilley J, Kubsad S, Liebelt E. Notes from the Field: Phenibut Exposures Reported to Poison Centers — United States, 2009–2019. MMWR Morb Mortal Wkly Rep 2020;69:1227–1228. DOI: http://dx.doi.org/10.15585/mmwr.mm6935a5external icon.
    22. U.S. Food and Drug Administration. FDA acts on dietary supplements containing DMHA and phenibut. FDA website. April 16, 2019. Accessed July 2021. Retrieved from https://www.fda.gov/food/cfsan-constituent-updates/fda-acts-dietary-supplements-containing-dmha-and-phenibut
    23. National Center for Biotechnology Information. PubChem Compound Summary for CID 14113, 4-Amino-3-phenylbutanoic acid. https://pubchem.ncbi.nlm.nih.gov/compound/4-Amino-3-phenylbutanoic-acid. Accessed July 9, 2021.
    24. Lapin I. Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug. CNS Drug Rev. 2001;7(4):471-481. doi:10.1111/j.1527-3458.2001.tb00211.x