View source for Phenibut

{{Short description|CNS depressant medication}}
{{Use dmy dates|date=October 2020}}
{{Infobox drug
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 464373947
| IUPAC_name = 4-Amino-3-phenylbutanoic acid
| image = Phenibut skeletal formula.svg
| image_class = skin-invert-image
| width = 200px
| image2 = Phenibut ball-and-stick model.png
| width2 = 200px

<!--Clinical data-->| tradename = Anvifen, Fenibut, Noofen, others<ref name="DrobizhevFedotova2016">{{cite journal | vauthors = Drobizhev MY, Fedotova AV, Kikta SV, Antohin EY | year = 2016 | title = Феномен аминофенилмасляной кислоты | trans-title = Phenomenon of aminophenylbutyric acid | url = https://www.rmj.ru/articles/nevrologiya/Fenomen_aminofenilmaslyanoy_kisloty/ | language = Russian | journal = Russian Medical Journal | volume = 2017 | issue = 24 | pages = 1657–1663 | issn = 1382-4368 | access-date = 16 September 2017 | archive-date = 16 September 2017 | archive-url = https://web.archive.org/web/20170916053610/https://www.rmj.ru/articles/nevrologiya/Fenomen_aminofenilmaslyanoy_kisloty/ | url-status = live }}</ref>
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| dependency_liability = 
| addiction_liability = 
| legal_AU = S4
| legal_CA = Unscheduled <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_DE = NPSG
| legal_US = Unapproved drug; use in [[dietary supplement]]s, [[food]], or [[medicine]] is unlawful.<ref>{{Cite journal |last=Nutrition |first=Center for Food Safety and Applied |date=2023-03-06 |title=Phenibut in Dietary Supplements |url=https://www.fda.gov/food/dietary-supplement-ingredient-directory/phenibut-dietary-supplements |journal=FDA |language=en |access-date=23 May 2023 |archive-date=23 May 2023 |archive-url=https://web.archive.org/web/20230523031247/https://www.fda.gov/food/dietary-supplement-ingredient-directory/phenibut-dietary-supplements |url-status=dead }}</ref>
| legal_UN = Unscheduled
| legal_status = <small>[[Russia|RU]]</small>:  Rx-only
| routes_of_administration = ''Common'': [[Oral administration|Oral]]<ref name="pmid26693960" /><br />''Uncommon'': [[Rectal administration|Rectal]]<ref name="pmid26693960" />
| class = [[GABA receptor agonist|GABA<sub>B</sub> receptor agonist]]; [[Gabapentinoid]]

<!--Pharmacokinetic data-->| bioavailability = ≥63% (250 mg)<ref name="pmid11830761" />
| protein_bound = 
| metabolism = [[Liver]] (minimal)<ref name="Phenibut-Label">{{citation | author = Ozon Pharm | title = Fenibut | access-date = 15 September 2017 | url = http://www.ozonpharm.ru/upload/iblock/608/nmntxzabdzjhlu%20-%20fbdoqpbtdj.ofzsxp%20tkbgeygfzj.pdf | archive-url = https://web.archive.org/web/20170916094855/http://www.ozonpharm.ru/upload/iblock/608/nmntxzabdzjhlu%20-%20fbdoqpbtdj.ofzsxp%20tkbgeygfzj.pdf | archive-date = 16 September 2017 | url-status = dead }}</ref><ref name="pmid11830761" />
| metabolites = Inactive<ref name="Phenibut-Label" />
| elimination_half-life = 5.3 hours (250 mg)<ref name="pmid11830761" />
| onset = [[Oral administration|Oral]]: 2–4 hours<ref name="pmid26693960" /><br />[[Rectal administration|Rectal]]: 20–30 minutes<ref name="pmid26693960" />
| duration_of_action = 15–24 hours (1–3 g)<ref name="pmid26693960" />
| excretion = [[Urine]]: 63% (unchanged)<ref name="pmid11830761" />

<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 1078-21-3
| CAS_supplemental = <br />3060-41-1 ([[hydrochloride]])
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = T2M58D6LA8
| ATC_prefix = N06
| ATC_suffix = BX22
| PubChem = 14113
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 13491
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 315818
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D10509
| synonyms = Aminophenylbutyric acid; Fenibut; Fenigam; Phenigam; Phenybut; Phenygam; Phenylgamma; Phenigama; PHG; PhGABA; β-Phenyl-γ-aminobutyric acid; β-Phenyl-GABA<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA69|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=69–}}</ref>

<!--Chemical data-->| C = 10
| H = 13
| N = 1
| O = 2
| SMILES = O=C(O)CC(c1ccccc1)CN
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H13NO2/c11-7-9(6-10(12)13)8-4-2-1-3-5-8/h1-5,9H,6-7,11H2,(H,12,13)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = DAFOCGYVTAOKAJ-UHFFFAOYSA-N

<!--Physical data-->| melting_point = 253
}}

<!-- Definition and medical uses -->
'''Phenibut''', sold under the brand name '''Anvifen''' among others,<ref name="DrobizhevFedotova2016" /> is a [[central nervous system]] (CNS) [[depressant]] with [[anxiolytic]] effects, and is used to treat [[anxiety]], [[insomnia]], and for a variety of other indications.<ref name="pmid11830761">{{cite journal | vauthors = Lapin I | title = Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug | journal = CNS Drug Reviews | volume = 7 | issue = 4 | pages = 471–81 | year = 2001 | pmid = 11830761 | pmc = 6494145 | doi = 10.1111/j.1527-3458.2001.tb00211.x }}</ref> It is usually taken [[oral administration|orally]] (swallowed by mouth), but may be given [[intravenously]].<ref name="Phenibut-Label" /><ref name="pmid11830761" />

<!-- Side effects and mechanism -->
Side effects of phenibut can include [[sedation]], [[sleepiness]], [[nausea]], [[irritability]], [[psychomotor agitation|agitation]], [[dizziness]], [[euphoria]], and sometimes [[headache]], among others.<ref name="Phenibut-Label" /><ref name="RLS-Phenibut" /> [[Overdose]] of phenibut can produce marked central nervous system depression including [[unconsciousness]].<ref name="Phenibut-Label" /><ref name="RLS-Phenibut" /> The medication is structurally related to the [[neurotransmitter]] [[γ-aminobutyric acid]] (GABA), and hence is a [[GABA analogue]].<ref name="pmid11830761" /> Phenibut is thought to act as a [[GABAB receptor|GABA<sub>B</sub> receptor]] [[agonist]], similarly to [[baclofen]] and [[γ-hydroxybutyrate]] (GHB).<ref name="pmid11830761" /> However, at low concentrations, phenibut mildly increases the concentration of [[dopamine]] in the brain, providing [[Stimulant|stimulatory]] effects in addition to the [[Anxiolytic|anxiolysis]].<ref>{{cite journal | vauthors = Lapin I | title = Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug | journal = CNS Drug Reviews | volume = 7 | issue = 4 | pages = 471–81 | date = 2006-06-07 | pmid = 11830761 | pmc = 6494145 | doi = 10.1111/j.1527-3458.2001.tb00211.x }}</ref>

<!-- History, society, and culture -->
Phenibut was developed in the [[Soviet Union]] and was introduced for medical use in the 1960s.<ref name="pmid11830761" /> Today, it is marketed for medical use in Russia, Ukraine, Belarus, Kazakhstan, and Latvia.<ref name="pmid11830761" /> The medication is not approved for clinical use in the United States and most of Europe, but it is sold on the Internet as a [[dietary supplement|supplement]] and purported [[nootropic]].<ref name="pmid26693960" /><ref name="ClinicalTox">{{cite journal | vauthors = Cohen PA, Ellison RR, Travis JC, Gaufberg SV, Gerona R | title = Quantity of phenibut in dietary supplements before and after FDA warnings | journal = Clinical Toxicology | volume = 60 | issue = 4 | pages = 486–488 | date = April 2022 | pmid = 34550038 | doi = 10.1080/15563650.2021.1973020 | s2cid = 237594860 }}</ref> Phenibut has been used [[recreational drug|recreationally]] and can produce [[euphoria]] as well as [[drug addiction|addiction]], [[drug dependence|dependence]], and [[drug withdrawal|withdrawal]].<ref name="pmid26693960" /> It is a [[controlled substance]] in Australia, and it has been suggested that its legal status should be reconsidered in Europe as well.<ref name="pmid26693960" /> In Germany, phenibut is not approved as a drug and, as a food supplement, is controlled under the German New Psychoactive Substances Act.<ref name="Anlage NpSG - Einzelnorm">{{Cite web |title=Anlage NpSG - Einzelnorm |url=https://www.gesetze-im-internet.de/npsg/anlage.html |access-date=2024-06-07 |website=www.gesetze-im-internet.de}}</ref>

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.<ref name="fda-23">{{cite web |title=Phenibut in Dietary Supplements |url=https://www.fda.gov/food/information-select-dietary-supplement-ingredients-and-other-substances/phenibut-dietary-supplements |publisher=US Food and Drug Administration |access-date=14 September 2024 |date=12 July 2023}}</ref> [[FDA warning letter]]s had been issued to supplement manufacturers marketing phenibut products as [[Adulterant|adulterated]].<ref name="fda-19">{{cite web |title=FDA Acts on Dietary Supplements Containing DMHA and Phenibut |url=https://www.fda.gov/food/cfsan-constituent-updates/fda-acts-dietary-supplements-containing-dmha-and-phenibut |publisher=US Food and Drug Administration |access-date=14 September 2024 |date=29 April 2019 |archive-date=14 June 2022 |archive-url=https://web.archive.org/web/20220614224615/https://www.fda.gov/food/cfsan-constituent-updates/fda-acts-dietary-supplements-containing-dmha-and-phenibut |url-status=dead }}</ref>

==Medical uses==
Phenibut is used in Russia, Ukraine, Belarus and Latvia as a [[pharmaceutical drug]] to treat [[anxiety]] and to improve [[sleep]] (e.g., in the treatment of [[insomnia]]).<ref name="pmid11830761" /><ref name="Phenibut-Label" /> It is also used for various other indications, including the treatment of [[asthenia]], [[depression (mood)|depression]], [[alcoholism]], [[alcohol withdrawal syndrome]], [[post-traumatic stress disorder]], [[stuttering]], [[tic]]s, [[vestibular disorder]]s, [[Ménière's disease]], [[dizziness]], for the prevention of [[motion sickness]], and for the prevention of anxiety before or after [[surgical procedure]]s or painful [[diagnostic test]]s.<ref name="Phenibut-Label" /><ref name="pmid11830761" />

===Available forms===
Phenibut is available as a medication in the form of 250&nbsp;mg or 500&nbsp;mg [[tablet (pharmacy)|tablet]]s for [[oral administration]] and as a [[Solution (chemistry)|solution]] at a [[concentration]] of 10&nbsp;mg/mL for [[infusion therapy|infusion]].<ref name="Phenibut-Label" /><ref name="RLS-Phenibut">{{cite web | author = Регистр лекарственных средств России ([Russian Medicines Register]) | title = Фенибут (Phenybutum) | trans-title = Fenibut (Phenybutum) | language = Russian | access-date = 15 September 2017 | url = https://www.rlsnet.ru/tn_index_id_5320.htm | archive-date = 3 March 2009 | archive-url = https://web.archive.org/web/20090303232933/https://www.rlsnet.ru/tn_index_id_5320.htm | url-status = live }}</ref><ref name="SivchikGrygoryan" /> In the US, dietary supplements labeled as containing phenibut have been found to contain zero to greater than 1,100&nbsp;mg of phenibut per serving.<ref name="ClinicalTox" />

==Contraindications==
[[Contraindication]]s of phenibut include:<ref name="Phenibut-Label" /><ref name="RLS-Phenibut" />
* [[Drug intolerance|Intolerance]] to phenibut
* [[Pregnancy]] and [[breastfeeding]]
* Children who are younger than two years of age
* [[Liver insufficiency]] or [[liver failure|failure]]
* [[Ulcerative]] [[lesion]]s of the [[gastrointestinal tract]]

Phenibut should not be combined with [[alcohol (drug)|alcohol]].<ref name="RLS-Phenibut" />

==Side effects==
Phenibut is generally well-[[tolerability|tolerated]].<ref name="pmid11830761" /><ref name="RLS-Phenibut" /> Possible [[side effect]]s may include [[sedation]], [[somnolence]], [[nausea]], [[irritability]], [[psychomotor agitation|agitation]], [[anxiety]], [[dizziness]], [[headache]], and [[allergic reaction]]s such as [[skin rash]] and [[itching]].<ref name="Phenibut-Label" /><ref name="RLS-Phenibut" /> At high doses, [[motor incoordination]], [[loss of balance]], and [[hangover]]s may occur.<ref name="pmid26693960" /> Due to its CNS depressant effects, people taking phenibut should refrain from potentially dangerous activities such as operating heavy machinery.<ref name="Phenibut-Label" /><ref name="RLS-Phenibut" /> With prolonged use of phenibut, particularly at high doses, the [[liver]] and [[blood]] should be [[medical monitoring|monitored]], due to risk of [[fatty liver disease]] and [[eosinophilia]].<ref name="Phenibut-Label" /><ref name="RLS-Phenibut" />

=== Dependence and withdrawal ===
[[Drug tolerance|Tolerance]] to phenibut easily develops with repeated use, leading to [[Substance dependence|dependence]].<ref name="pmid11830761" />{{Update inline|date=August 2023}} [[Drug withdrawal|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 hallucination|visual]] and [[auditory hallucination]]s, and acute [[psychosis]].<ref name="pmid26693960" /> Baclofen has successfully been used for treatment of phenibut dependence.<ref>{{cite journal |vauthors=Samokhvalov AV, Paton-Gay CL, Balchand K, Rehm J |date=February 2013 |title=Phenibut dependence |journal=BMJ Case Reports |volume=2013 |pages=bcr2012008381 |doi=10.1136/bcr-2012-008381 |pmc=3604470 |pmid=23391959}}</ref>

==Overdose==
In [[overdose]], phenibut can cause severe [[drowsiness]], [[nausea]], [[vomiting]], [[eosinophilia]], [[hypotension|lowered blood pressure]], [[renal impairment]], and, above 7&nbsp;grams, [[fatty liver disease|fatty liver degeneration]].<ref name="Phenibut-Label" /><ref name="RLS-Phenibut" /> There are no specific [[antidote]]s for phenibut overdose.<ref name="RLS-Phenibut" /> [[Lethargy]], [[somnolence]], [[psychomotor agitation|agitation]], [[delirium]], [[tonic–clonic seizure]]s, [[unconsciousness|reduced consciousness or unconsciousness]], and [[unresponsiveness]] have been reported in recreational users who have overdosed.<ref name="pmid26693960" /> Management of phenibut overdose includes [[activated charcoal (medication)|activated charcoal]], [[gastric lavage]], induction of vomiting, and symptom-based treatment.<ref name="Phenibut-Label" /><ref name="RLS-Phenibut" /> There have been three associated deaths which found Phenibut in the users system but only one of these cases solely included Phenibut.<ref>{{cite journal | vauthors = Graves JM, Dilley J, Kubsad S, Liebelt E | title = Notes from the Field: Phenibut Exposures Reported to Poison Centers - United States, 2009–2019 | language = en-us | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 69 | issue = 35 | pages = 1227–1228 | date = September 2020 | pmid = 32881852 | pmc = 7470459 | doi = 10.15585/mmwr.mm6935a5 | doi-access = free }}</ref>

== Interactions ==

Phenibut may mutually potentiate and extend the duration of the effects of other CNS depressants, including [[anxiolytic]]s, [[antipsychotic]]s, [[sedative]]s, [[opioid]]s, [[anticonvulsant]]s, and [[alcohol (drug)|alcohol]].<ref name="Phenibut-Label" /><ref name="RLS-Phenibut" />

==Pharmacology==
{{See also|Gabapentinoid#Pharmacology}}

===Pharmacodynamics===
{| class="wikitable floatright"
|-
|+ GABA and analogues<br />at biological targets<ref name="pmid6297646">{{cite journal | vauthors = Bowery NG, Hill DR, Hudson AL | title = Characteristics of GABAB receptor binding sites on rat whole brain synaptic membranes | journal = British Journal of Pharmacology | volume = 78 | issue = 1 | pages = 191–206 | date = January 1983 | pmid = 6297646 | pmc = 2044790 | doi = 10.1111/j.1476-5381.1983.tb09380.x }}</ref>
|-
! Compound !! [[GABAB receptor|GABA<sub>B</sub>]] !! [[GABAA receptor|GABA<sub>A</sub>]]
|-
| {{abbrlink|GABA|γ-Aminobutyric acid}} || 0.08 || 0.12
|-
| {{abbrlink|GHB|γ-Hydroxybutyric acid}} || >100 || >100
|-
| {{abbrlink|GABOB|γ-Amino-β-hydroxybutyric acid}} || 1.10 || 1.38
|-
| Phenibut || 9.6 || >100
|-
| [[4-Fluorophenibut|4-F-phenibut]] || 1.70 || >100
|-
| [[Baclofen]] || 0.13 || >100
|-
| &nbsp;&nbsp;[[Baclofen|(''R'')-Baclofen]] || 0.13 || >100
|-
| &nbsp;&nbsp;[[Baclofen|(''S'')-Baclofen]] || 74.0 || >100
|- class="sortbottom"
| colspan="3" | Values are [[IC50|IC<sub>50</sub>]] (μM) in rat brain.
|}

Phenibut acts as a [[full agonist]] of the [[GABAB receptor|GABA<sub>B</sub> receptor]], similarly to [[baclofen]].<ref name="AcademicPress2010">{{cite book|title=GABAb Receptor Pharmacology: A Tribute to Norman Bowery: A Tribute to Norman Bowery|url=https://books.google.com/books?id=_iMDQOA2UIsC&pg=PA25|date=21 September 2010|publisher=Academic Press|isbn=978-0-12-378648-7|pages=25–}}</ref><ref name="pmid18275958">{{cite journal | vauthors = Dambrova M, Zvejniece L, Liepinsh E, Cirule H, Zharkova O, Veinberg G, Kalvinsh I | title = Comparative pharmacological activity of optical isomers of phenibut | journal = European Journal of Pharmacology | volume = 583 | issue = 1 | pages = 128–134 | date = March 2008 | pmid = 18275958 | doi = 10.1016/j.ejphar.2008.01.015 }}</ref> It has between 30- and 68-fold lower [[affinity (pharmacology)|affinity]] for the GABA<sub>B</sub> receptor than baclofen, and, in accordance, is used at far higher doses in comparison.<ref name="AcademicPress2010" /> (''R'')-Phenibut has more than 100-fold higher affinity for the GABA<sub>B</sub> receptor than does (''S'')-phenibut; hence, (''R'')-phenibut is the active enantiomer at the GABA<sub>B</sub> receptor.<ref name="AllanBates1990">{{cite journal | vauthors = Allan RD, Bates MC, Drew CA, Duke RK, Hambley TW, Johnston GA, Mewett KN, Spence I | display-authors= 6 |title=A new synthesis resolution and in vitro activities of (R)- and (S)-β-Phenyl-Gaba|journal=Tetrahedron|volume=46|issue=7|year=1990|pages=2511–2524|issn=0040-4020|doi=10.1016/S0040-4020(01)82032-9}}</ref>

{| class="wikitable floatright"
|-
|+ <br />Phenibut and analogues<br />at biological targets<ref name="pmid26234470">{{cite journal | vauthors = Zvejniece L, Vavers E, Svalbe B, Veinberg G, Rizhanova K, Liepins V, Kalvinsh I, Dambrova M | display-authors = 6 | title = R-phenibut binds to the α2-δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects | journal = Pharmacology, Biochemistry, and Behavior | volume = 137 | pages = 23–9 | date = October 2015 | pmid = 26234470 | doi = 10.1016/j.pbb.2015.07.014 | s2cid = 42606053 }}</ref>
|-
! Compound !! [[Voltage-dependent calcium channel#.CE.B12.CE.B4 Subunit|{{abbr|α<sub>2</sub>δ|α2δ subunit-containing voltage-dependent calcium channels}}]] !! [[GABAB receptor|GABA<sub>B</sub>]]
|-
| Phenibut || {{abbr|ND|No data}} || 177
|-
| &nbsp;&nbsp;(''R'')-Phenibut || 23 || 92
|-
| &nbsp;&nbsp;(''S'')-Phenibut || 39 || >1,000
|-
| [[Baclofen]] || 156 || 6
|-
| [[Gabapentin]] || 0.05 || >1,000
|- class="sortbottom"
| colspan="3" | Values are K<sub>i</sub> (μM) in rat brain.
|}

Phenibut also binds to and blocks [[Voltage-dependent calcium channel#α2δ Subunit|α<sub>2</sub>δ subunit]]-containing VDCCs, similarly to [[gabapentin]] and [[pregabalin]], and hence is a [[gabapentinoid]].<ref name="pmid26234470" /><ref name="pmid26621244">{{cite journal | vauthors = Vavers E, Zvejniece L, Svalbe B, Volska K, Makarova E, Liepinsh E, Rizhanova K, Liepins V, Dambrova M | display-authors = 6 | title = The neuroprotective effects of R-phenibut after focal cerebral ischemia | journal = Pharmacological Research | volume = 113 | issue = Pt B | pages = 796–801 | date = November 2016 | pmid = 26621244 | doi = 10.1016/j.phrs.2015.11.013 }}</ref> Both (''R'')-phenibut and (''S'')-phenibut display this action with similar [[affinity (pharmacology)|affinity]] (K<sub>i</sub> = 23 and 39&nbsp;μM, respectively).<ref name="pmid26234470" />

It is often claimed on websites about [[nootropic]]s 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.<ref name="dopaminw">{{cite journal |last1=Lapin |first1=Izyaslav |title=Phenibut (β-Phenyl-GABA): A Tranquilizer and Nootropic Drug |journal=CNS Drug Reviews |date=December 2001 |volume=7 |issue=4 |pages=471–481 |doi=10.1111/j.1527-3458.2001.tb00211.x|pmid=11830761 |pmc=6494145 }}</ref> The mechanism underlying this putative effect is unclear.<ref name="dopaminw"/> Structurally, phenibut can also be considered a derivative of [[phenethylamine]], and some research suggests that phenibut antagonizes the action of phenethylamine.<ref name="dopaminw"/>

===Pharmacokinetics===
Little information thus far has been published on the clinical [[pharmacokinetics]] of phenibut.<ref name="pmid11830761" /> The drug is reported to be well-[[absorption (pharmacokinetics)|absorbed]].<ref name="Phenibut-Label" /> It [[distribution (pharmacology)|distribute]]s widely throughout the body and across the [[blood–brain barrier]].<ref name="Phenibut-Label" /> Approximately 0.1% of an administered dose of phenibut reportedly penetrates into the [[brain]], with this said to occur to a much greater extent in young people and the elderly.<ref name="Phenibut-Label" /> Following a single 250&nbsp;mg dose in healthy volunteers, its [[elimination half-life]] was approximately 5.3&nbsp;hours and the drug was largely (63%) [[excretion|excreted]] in the [[urine]] unchanged.<ref name="pmid11830761" />

Some limited information has been described on the pharmacokinetics of phenibut in recreational users taking much higher doses (e.g., 1–3&nbsp;grams) than typical clinical doses.<ref name="pmid26693960">{{cite journal | vauthors = Owen DR, Wood DM, Archer JR, Dargan PI | title = Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects and acute toxicity | journal = Drug and Alcohol Review | volume = 35 | issue = 5 | pages = 591–6 | date = September 2016 | pmid = 26693960 | doi = 10.1111/dar.12356 | hdl-access = free | hdl = 10044/1/30073 }}</ref><ref name="pmid25655145">{{cite journal | vauthors = Schifano F, Orsolini L, Duccio Papanti G, Corkery JM | title = Novel psychoactive substances of interest for psychiatry | journal = World Psychiatry | volume = 14 | issue = 1 | pages = 15–26 | date = February 2015 | pmid = 25655145 | pmc = 4329884 | doi = 10.1002/wps.20174 }}</ref> In these individuals, the [[onset of action]] of phenibut has been reported to be 2 to 4&nbsp;hours orally and 20 to 30&nbsp;minutes [[rectal administration|rectal]]ly, the [[Cmax (pharmacology)|peak effects]] are described as occurring 4 to 6&nbsp;hours following oral ingestion, and the total [[duration of action|duration]] for the oral route has been reported to be 15 to 24&nbsp;hours (or about 3 to 5 terminal half-lives).<ref name="pmid26693960" />

==Chemistry==
Phenibut is a [[synthetic compound|synthetic]] [[aromatic amino acid]]. It is a [[chirality (chemistry)|chiral molecule]] and thus has two potential [[absolute configuration|configuration]]s, as (''R'')- and (''S'')-[[enantiomer]]s.<ref name="pmid18275958" />

===Structure and analogues===
[[File:Phenibut and analogues.png|class=skin-invert-image|thumb|right|350px|Chemical structures of phenibut and analogues.]]

Phenibut is a [[chemical derivative|derivative]] of the [[inhibitory postsynaptic potential|inhibitory]] neurotransmitter [[GABA]].<ref name="pmid11830761" /> Hence, it is a [[GABA analogue]].<ref name="pmid11830761" /> Phenibut is specifically the [[structural analog|analogue]] of GABA with a [[phenyl ring]] substituted in at the β-position.<ref name="pmid11830761" /> As such, its chemical name is β-phenyl-γ-aminobutyric acid, which can be abbreviated as β-phenyl-GABA.<ref name="pmid11830761" /> The presence of the phenyl ring allows phenibut to cross the [[blood–brain barrier]] significantly, unlike GABA.<ref name="pmid11830761" /> Phenibut also contains the [[trace amine]] [[β-phenethylamine]] in its [[chemical structure|structure]].<ref name="pmid11830761" />

Phenibut is closely related to a variety of other GABA analogues including [[baclofen]] (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), and [[GABOB]] (β-hydroxy-GABA).<ref name="pmid11830761" /><ref name="pmid26234470" /> It has almost the same chemical structure as baclofen, differing from it only in having a [[hydrogen]] atom instead of a [[chlorine]] atom at the ''para'' position of the phenyl ring.<ref name="pmid11830761" /> Phenibut is also close in structure to pregabalin, which has an [[isobutane|isobutyl]] group at the β position instead of phenibut's phenyl ring.<ref name="pmid26234470" />

A [[glutamate]]-derivative analogue of phenibut is [[glufimet]] (dimethyl 3-phenylglutamate hydrochloride).<ref name="pmid28726197">{{cite journal | vauthors = Perfilova VN, Popova TA, Prokofiev II, Mokrousov IS, Ostrovskii OV, Tyurenkov IN | title = 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 | journal = Bulletin of Experimental Biology and Medicine | volume = 163 | issue = 2 | pages = 226–229 | date = June 2017 | pmid = 28726197 | doi = 10.1007/s10517-017-3772-4 | s2cid = 4907409 }}</ref>

===Synthesis===
A [[chemical synthesis]] of phenibut has been published.<ref name="SivchikGrygoryan">{{citation | vauthors = Sivchik VV, Grygoryan HO, Survilo VL, Trukhachova TV | title = Синтез γ-амино-β-фенилмасляной кислоты (фенибута) | trans-title = Synthesis of β-phenyl-γ-aminobutyric acid (phenibut) | language = Russian | year = 2012 | url = http://elib.bsu.by/bitstream/123456789/15950/1/C%D0%91%D0%9E%D0%A0%D0%9D%D0%98%D0%9A%202012.pdf#page=448 | access-date = 16 September 2017 | archive-date = 16 September 2017 | archive-url = https://web.archive.org/web/20170916095410/http://elib.bsu.by/bitstream/123456789/15950/1/C%D0%91%D0%9E%D0%A0%D0%9D%D0%98%D0%9A%202012.pdf#page=448 | url-status = live }}</ref>

==History==
Phenibut was synthesized at the [[Herzen University|A. I. Herzen Leningrad Pedagogical Institute]] ([[USSR]]) by Professor [[Vsevolod Perekalin]]'s team and tested at the Institute of Experimental Medicine, USSR Academy of Medical Sciences.<ref name="pmid11830761" /> It was introduced into clinical use in Russia in the 1960s.<ref name="pmid11830761" />

==Society and culture==
[[File:Phenibut from Russia.png|thumb|right|225px|[[Olainfarm]]'s pharmaceutical phenibut sold in Russia.]]

===Other names===
Alternate spellings include ''fenibut'' and ''phenybut''.<ref name="Elks2014" /> It is also sometimes referred to as ''aminophenylbutyric acid''.<ref name="DrobizhevFedotova2016" /> The word ''phenibut'' is a contraction of the chemical name of the drug, ''β-'''pheny'''l-γ-amino'''but'''yric acid''.<ref name="pmid11830761" /> In early publications, phenibut was referred to as ''fenigam'' and ''phenigama''.<ref name="pmid11830761" /><ref name="KhauninaLapin1976">{{cite journal| vauthors = Khaunina RA, Lapin IP |title=Fenibut, a new tranquilizer |journal=Pharmaceutical Chemistry Journal |volume=10 |issue=12 |year=1976 |pages=1703–1705 |issn=0091-150X |doi=10.1007/BF00760021 |s2cid=29071385}}</ref> The drug has not been assigned an {{abbrlink|INN|International Nonproprietary Name}}.<ref name="Elks2014" /><ref name="Phenibut-Label" />

===Brand names===
Phenibut is marketed in [[Russia]], [[Ukraine]], [[Belarus]], and [[Latvia]] under the brand names Anvifen, Fenibut, Bifren, and Noofen ([[Russian language|Russian]]: Анвифен, Фенибут, Бифрен and Ноофен, respectively).<ref name="DrobizhevFedotova2016" />

===Availability===
Phenibut is approved in [[Russia]], [[Ukraine]], [[Belarus]], and [[Latvia]] for medical use.<ref name="pmid26693960" /> It is not approved or available as a [[pharmaceutical drug|medication]] in other countries in the [[European Union]], the [[United States]], or [[Australia]].<ref name="pmid26693960" /> In countries where phenibut is not a licensed pharmaceutical drug, it is sold online [[over-the-counter|without a prescription]] as a "[[nutritional supplement]]".<ref name="pmid26693960" /><ref name="ClinicalTox" /> It is often used as a form of [[self-medication]] for [[social anxiety]].<ref name="pmid26693960" />

===Recreational use===
Phenibut is used [[recreational drug use|recreationally]] due to its ability to produce [[euphoria]], [[anxiolysis]], and increased [[sociability]],<ref name="pmid26693960" /> 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.<ref name="pmid26693960" /> Recreational users usually take the drug [[Oral administration|orally]]; there are a few case reports of rectal administration and one report of [[Insufflation (medicine)|insufflation]], which was described as "very painful" and causing swollen [[nostril]]s.<ref name="pmid26693960" />

===Legal status===
As of 2021, phenibut is a [[controlled substance]] in Australia,<ref name="pmid26693960"/> France,<ref>Par [https://www.legifrance.gouv.fr/codes/article_lc/LEGIARTI000032106035/] {{Webarchive|url=https://web.archive.org/web/20210508163545/https://www.legifrance.gouv.fr/codes/article_lc/LEGIARTI000032106035/|date=8 May 2021}} La liste des substances psychotropes</ref> Hungary,<ref>{{Cite web|url=http://kozlonyok.hu/nkonline/MKPDF/hiteles/MK18170.pdf|title=39/2018. (XI. 8.) EMMI rendelet Az új pszichoaktív anyaggá minősített anyagokról vagy vegyületcsoportokról szóló 55/2014. (XII. 30.) EMMI rendelet módosításáról|access-date=14 November 2018|archive-date=14 November 2018|archive-url=https://web.archive.org/web/20181114141557/http://kozlonyok.hu/nkonline/MKPDF/hiteles/MK18170.pdf|url-status=live}}</ref> Italy,<ref name="Gazzetta Ufficiale 11/08/20">{{cite web | url= https://www.gazzettaufficiale.it/eli/id/2020/08/21/20A04540/SG | title= Gazzetta Ufficiale 11/08/20 | publisher= Lorenzo Arbolino | date= 11 August 2020 | access-date= 27 August 2020 | archive-date= 2 May 2024 | archive-url= https://web.archive.org/web/20240502165522/https://www.gazzettaufficiale.it/eli/id/2020/08/21/20A04540/SG | url-status= live }}</ref> Lithuania,<ref>{{Cite web|url=http://ntakd.lrv.lt/lt/naujienos/rinkos-ribojimo-priemones-fenibutui|title=RINKOS RIBOJIMO PRIEMONĖS FENIBUTUI!|website=ntakd.lrv.lt|language=lt|access-date=2020-01-27|archive-date=6 October 2021|archive-url=https://web.archive.org/web/20211006065759/https://ntakd.lrv.lt/lt/naujienos/rinkos-ribojimo-priemones-fenibutui|url-status=dead}}</ref><ref name=":0">{{Cite web|url=https://e-seimas.lrs.lt/portal/legalAct/lt/TAD/9aff1ef11ce911eaadfcfdb735b57421?jfwid=-bgd9aafbv|title=V-1431 Dėl Lietuvos Respublikos sveikatos apsaugos ministro 2000 m. sausio 6 d. įsakymo Nr. 5 "Dėl Narko...|website=e-seimas.lrs.lt|language=lt|access-date=2020-01-27|archive-date=27 January 2020|archive-url=https://web.archive.org/web/20200127002637/https://e-seimas.lrs.lt/portal/legalAct/lt/TAD/9aff1ef11ce911eaadfcfdb735b57421%3Fjfwid%3D-bgd9aafbv|url-status=live}}</ref> and Germany<ref name="Anlage NpSG - Einzelnorm"/> where, nevertheless, it is readily obtained online.<ref>{{Cite journal |vauthors=Bonnet U, Scherbaum N, Schaper A, Soyka M|title=Phenibut — an Illegal Food Supplement With Psychotropic Effects and Health Risks|date=5 April 2024 |doi= 10.3238/arztebl.m2024.0003|volume=121|pages=222–7|url=https://www.aerzteblatt.de/int/archive/article?id=238384 |journal=Deutsches Ärzteblatt International|issue=7 |pmid=38377332 |language=en|pmc=11539871}}</ref>

In 2015, it was suggested that the legal status of phenibut in Europe should be reconsidered due to its recreational potential.<ref name="pmid26693960" /> In February 2018, the Australian [[Therapeutic Goods Administration]] declared it a prohibited (schedule 9) substance, citing health concerns due to withdrawal and overdose.<ref>{{cite web|publisher=Australian Government Department of Health.|work=Administration Therapeutic Goods Administration|title=3.3 Phenibut|url=https://www.tga.gov.au/book-page/33-phenibut|access-date=6 November 2017|language=en|date=31 October 2017|archive-date=27 March 2020|archive-url=https://web.archive.org/web/20200327065227/https://www.tga.gov.au/book-page/33-phenibut|url-status=live}}</ref><ref>{{cite news | url= http://www.abc.net.au/news/2018-02-22/detectives-probe-if-drug-behind-school-overdose-bought-online/9471958 | title= Mass school overdose investigation focuses on banned Russian drug | newspaper= ABC News | publisher= Australian Broadcasting Corporation | date= 22 February 2018 | access-date= 22 February 2018 | archive-date= 22 February 2018 | archive-url= https://web.archive.org/web/20180222023735/http://www.abc.net.au/news/2018-02-22/detectives-probe-if-drug-behind-school-overdose-bought-online/9471958 | url-status= live }}</ref>

As of 14 November 2018, Hungary added phenibut and 10 other items to its New Psychoactive Substances ban list,<ref>{{cite web | url= https://net.jogtar.hu/jogszabaly?docid=A1400055.EMM | title= EMMI Decree substances or groups of compounds classified as new psychoactive substances | publisher= Wolters Kluwer | date= 1 January 2015 | access-date= 5 August 2020 | archive-date= 8 August 2020 | archive-url= https://web.archive.org/web/20200808213352/https://net.jogtar.hu/jogszabaly?docid=A1400055.EMM | url-status= dead }}</ref> and, as of 26 August 2020, Italy added phenibut to its New Psychoactive Substances ban list.<ref name="Gazzetta Ufficiale 11/08/20"/> As of 18 September 2020, France added phenibut to the controlled psychoactive substances list, prohibiting production, sale, storage, and use.<ref>{{Cite web |url=https://www.legeneraliste.fr/actu-medicale/sante-publique/le-phenibut-interdit-en-france |title=Le phénibut interdit en France {{!}} Le Généraliste |work=Le Généraliste |access-date=28 April 2021 |archive-date=22 January 2021 |archive-url=https://web.archive.org/web/20210122213622/https://www.legeneraliste.fr/actu-medicale/sante-publique/le-phenibut-interdit-en-france |url-status=live }}</ref>

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.<ref>{{cite journal |vauthors=Penzak SR, Bulloch M |title=Phenibut: Review and Pharmacologic Approaches to Treating Withdrawal |journal=J Clin Pharmacol |volume=64 |issue=6 |pages=652–671 |date=June 2024 |pmid=38339875 |doi=10.1002/jcph.2414 |type=Review}}</ref><ref>{{cite journal |vauthors=Jouney EA |title=Phenibut (β-Phenyl-γ-Aminobutyric Acid): an Easily Obtainable "Dietary Supplement" With Propensities for Physical Dependence and Addiction |journal=Curr Psychiatry Rep |volume=21 |issue=4 |pages=23 |date=March 2019 |pmid=30852710 |doi=10.1007/s11920-019-1009-0 |url=}}</ref>

In [[Alabama]], phenibut was made a [[Controlled Substances Act#Schedule II controlled substances|Schedule II substance]] at the state level in November 2021.<ref>{{cite web|url=https://www.alabamapublichealth.gov/blog/assets/controlledsubstanceslist.pdf|title=Controlled Substances List; Schedule II, page 70|date=22 February 2024|publisher=Alabama State Board of Health|accessdate=13 September 2024|archive-date=8 August 2024|archive-url=https://web.archive.org/web/20240808233205/https://www.alabamapublichealth.gov/blog/assets/controlledsubstanceslist.pdf|url-status=live}}</ref>

==See also==
* [[Gabapentin]] 
* [[Pregabalin]]
* [[4-Fluorophenibut]]
* [[List of Russian drugs]]

==References==
{{Reflist|30em}}

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