Phenibut was developed in theSoviet Union and was introduced for medical use in the 1960s.[5] Today, it is marketed for medical use in Russia, Ukraine, Belarus, Kazakhstan, and Latvia.[5] The medication is not approved for clinical use in the United States and most of Europe, but it is sold on the Internet as asupplement and purportednootropic.[3][9] Phenibut has been usedrecreationally and can produceeuphoria as well asaddiction,dependence, andwithdrawal.[3] It is acontrolled substance in Australia, and it has been suggested that its legal status should be reconsidered in Europe as well.[3] In Germany, phenibut is not approved as a drug and, as a food supplement, is controlled under the German New Psychoactive Substances Act.[10]
In a 2023 assessment, the U.S.Food and Drug Administration (FDA) determined that phenibut does not meet the definition of a dietary ingredient, thereby making phenibut supplement products misbranded and illegal for marketing.[11]FDA warning letters had been issued to supplement manufacturers marketing phenibut products asadulterated.[12]
Phenibut is available as a medication in the form of 250 mg or 500 mgtablets fororal administration and as asolution at aconcentration of 10 mg/mL forinfusion.[6][7][13] In the US, dietary supplements labeled as containing phenibut have been found to contain zero to greater than 1,100 mg of phenibut per serving.[9]
Tolerance to phenibut easily develops with repeated use, leading todependence.[5][needs update]Withdrawal symptoms may occur upon discontinuation, and, in recreational users taking high doses, have been reported to include severe rebound anxiety,insomnia, aggresion, irritability, agitation,visual andauditory hallucinations, and acutepsychosis.[3] Baclofen has successfully been used for treatment of phenibut dependence.[14]
Phenibut acts as afull agonist of theGABAB receptor, similarly tobaclofen.[17][18] It has between 30- and 68-fold loweraffinity for the GABAB receptor than baclofen, and, in accordance, is used at far higher doses in comparison.[17] (R)-Phenibut has more than 100-fold higher affinity for the GABAB receptor than does (S)-phenibut; hence, (R)-phenibut is the active enantiomer at the GABAB receptor.[19]
It is often claimed on websites aboutnootropics and elsewhere on the internet that phenibut increases dopamine. Three papers published in Russian by Soviet scientists in 1979, 1986, and 1990 report that phenibut increases dopamine in the striatum of rats and in the mouse brain.[22] The mechanism underlying this putative effect is unclear.[22] Structurally, phenibut can also be considered a derivative ofphenethylamine, and some research suggests that phenibut antagonizes the action of phenethylamine.[22]
Little information thus far has been published on the clinicalpharmacokinetics of phenibut.[5] The drug is reported to be well-absorbed.[6] Itdistributes widely throughout the body and across theblood–brain barrier.[6] Approximately 0.1% of an administered dose of phenibut reportedly penetrates into thebrain, with this said to occur to a much greater extent in young people and the elderly.[6] Following a single 250 mg dose in healthy volunteers, itselimination half-life was approximately 5.3 hours and the drug was largely (63%)excreted in theurine unchanged.[5]
Some limited information has been described on the pharmacokinetics of phenibut in recreational users taking much higher doses (e.g., 1–3 grams) than typical clinical doses.[3][23] In these individuals, theonset of action of phenibut has been reported to be 2 to 4 hours orally and 20 to 30 minutesrectally, thepeak effects are described as occurring 4 to 6 hours following oral ingestion, and the totalduration for the oral route has been reported to be 15 to 24 hours (or about 3 to 5 terminal half-lives).[3]
Phenibut is closely related to a variety of other GABA analogues includingbaclofen (β-(4-chlorophenyl)-GABA),4-fluorophenibut (β-(4-fluorophenyl)-GABA),tolibut (β-(4-methylphenyl)-GABA),pregabalin ((S)-β-isobutyl-GABA),gabapentin (1-(aminomethyl)cyclohexane acetic acid), andGABOB (β-hydroxy-GABA).[5][20] It has almost the same chemical structure as baclofen, differing from it only in having ahydrogen atom instead of achlorine atom at thepara position of the phenyl ring.[5] Phenibut is also close in structure to pregabalin, which has anisobutyl group at the β position instead of phenibut's phenyl ring.[20]
Aglutamate-derivative analogue of phenibut isglufimet (dimethyl 3-phenylglutamate hydrochloride).[24]
Alternate spellings includefenibut andphenybut.[2] It is also sometimes referred to asaminophenylbutyric acid.[1] The wordphenibut is a contraction of the chemical name of the drug,β-phenyl-γ-aminobutyric acid.[5] In early publications, phenibut was referred to asfenigam andphenigama.[5][25] The drug has not been assigned anINNTooltip International Nonproprietary Name.[2][6]
Phenibut is marketed inRussia,Ukraine,Belarus, andLatvia under the brand names Anvifen, Fenibut, Bifren, and Noofen (Russian: Анвифен, Фенибут, Бифрен and Ноофен, respectively).[1]
Phenibut is usedrecreationally due to its ability to produceeuphoria,anxiolysis, and increasedsociability,[3] as well as remaining undetected in routine urinalysis. Because of its delayed onset of effects, first-time users often mistakenly take an additional dose of phenibut in the belief that the initial dose did not work.[3] Recreational users usually take the drugorally; there are a few case reports of rectal administration and one report ofinsufflation, which was described as "very painful" and causing swollennostrils.[3]
In 2015, it was suggested that the legal status of phenibut in Europe should be reconsidered due to its recreational potential.[3] In February 2018, the AustralianTherapeutic Goods Administration declared it a prohibited (schedule 9) substance, citing health concerns due to withdrawal and overdose.[32][33]
As of 14 November 2018, Hungary added phenibut and 10 other items to its New Psychoactive Substances ban list,[34] and, as of 26 August 2020, Italy added phenibut to its New Psychoactive Substances ban list.[28] As of 18 September 2020, France added phenibut to the controlled psychoactive substances list, prohibiting production, sale, storage, and use.[35]
In the United States, phenibut is an unapproved drug, but is often misleadingly marketed as a dietary supplement. It is readily available without a prescription.[36][37]
^abcdDrobizhev MY, Fedotova AV, Kikta SV, Antohin EY (2016)."Феномен аминофенилмасляной кислоты" [Phenomenon of aminophenylbutyric acid].Russian Medical Journal (in Russian).2017 (24):1657–1663.ISSN1382-4368.Archived from the original on 16 September 2017. Retrieved16 September 2017.
^abcdefghijklmРегистр лекарственных средств России ([Russian Medicines Register])."Фенибут (Phenybutum)" [Fenibut (Phenybutum)] (in Russian).Archived from the original on 3 March 2009. Retrieved15 September 2017.
^abcCohen PA, Ellison RR, Travis JC, Gaufberg SV, Gerona R (April 2022). "Quantity of phenibut in dietary supplements before and after FDA warnings".Clinical Toxicology.60 (4):486–488.doi:10.1080/15563650.2021.1973020.PMID34550038.S2CID237594860.
^abSivchik VV, Grygoryan HO, Survilo VL, Trukhachova TV (2012),Синтез γ-амино-β-фенилмасляной кислоты (фенибута) [Synthesis of β-phenyl-γ-aminobutyric acid (phenibut)](PDF) (in Russian),archived(PDF) from the original on 16 September 2017, retrieved16 September 2017
^abDambrova M, Zvejniece L, Liepinsh E, Cirule H, Zharkova O, Veinberg G, Kalvinsh I (March 2008). "Comparative pharmacological activity of optical isomers of phenibut".European Journal of Pharmacology.583 (1):128–134.doi:10.1016/j.ejphar.2008.01.015.PMID18275958.
^Allan RD, Bates MC, Drew CA, Duke RK, Hambley TW, Johnston GA, et al. (1990). "A new synthesis resolution and in vitro activities of (R)- and (S)-β-Phenyl-Gaba".Tetrahedron.46 (7):2511–2524.doi:10.1016/S0040-4020(01)82032-9.ISSN0040-4020.
^abcdeZvejniece L, Vavers E, Svalbe B, Veinberg G, Rizhanova K, Liepins V, et al. (October 2015). "R-phenibut binds to the α2-δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects".Pharmacology, Biochemistry, and Behavior.137:23–9.doi:10.1016/j.pbb.2015.07.014.PMID26234470.S2CID42606053.
^Vavers E, Zvejniece L, Svalbe B, Volska K, Makarova E, Liepinsh E, et al. (November 2016). "The neuroprotective effects of R-phenibut after focal cerebral ischemia".Pharmacological Research.113 (Pt B):796–801.doi:10.1016/j.phrs.2015.11.013.PMID26621244.
^Perfilova VN, Popova TA, Prokofiev II, Mokrousov IS, Ostrovskii OV, Tyurenkov IN (June 2017). "Effect of Phenibut and Glufimet, a Novel Glutamic Acid Derivative, on Respiration of Heart and Brain Mitochondria from Animals Exposed to Stress against the Background of Inducible NO-Synthase Blockade".Bulletin of Experimental Biology and Medicine.163 (2):226–229.doi:10.1007/s10517-017-3772-4.PMID28726197.S2CID4907409.
^"3.3 Phenibut".Administration Therapeutic Goods Administration. Australian Government Department of Health. 31 October 2017.Archived from the original on 27 March 2020. Retrieved6 November 2017.
^Penzak SR, Bulloch M (June 2024). "Phenibut: Review and Pharmacologic Approaches to Treating Withdrawal".J Clin Pharmacol (Review).64 (6):652–671.doi:10.1002/jcph.2414.PMID38339875.
^Jouney EA (March 2019). "Phenibut (β-Phenyl-γ-Aminobutyric Acid): an Easily Obtainable "Dietary Supplement" With Propensities for Physical Dependence and Addiction".Curr Psychiatry Rep.21 (4): 23.doi:10.1007/s11920-019-1009-0.PMID30852710.
