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Phenibut (4-Amino-3-Phenyl-Butyric Acid): Availability, Prevalence of Use, Desired Effects and Acute Toxicity

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Phenibut (4-Amino-3-Phenyl-Butyric Acid): Availability, Prevalence of Use, Desired Effects and Acute Toxicity bs_bs_banner REVIEW Drug and Alcohol Review (2015) DOI: 10.1111/dar.12356 Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects and acute toxicity DAVID R. OWEN1,DAVIDM.WOOD2,3,JOHNR.H.ARCHER2 & PAUL I. DARGAN2,3 1Division of Brain Sciences, Imperial College London, London, UK, 2Clinical Toxicology, Guy’s and St Thomas’ NHS Foundation Trust and King’s Health Partners, London, UK, and 3Faculty of Life Sciences and Medicine, King’sCollege London, London, UK Abstract Introduction and Aims. There has been a global increase in the availability and use of novel psychoactive substances (NPS) over the last decade. Phenibut (β-phenyl-γ-aminobutyric acid) is a GABAB agonist that is used as an NPS. Here, we bring together published scientific and grey information sources to further understand the prevalence of use, desired effects and acute toxicity of phenibut. Design and Methods. Using European Monitoring Centre for Drugs and Drug Addiction Internet snapshot method- ology, we undertook an English language Internet snapshot survey in May 2015 to gather information on the availability and price of phenibut from Internet NPS retailers. To gather information on prevalence of use, desired effects and/or adverse effects, we searched grey literature (online drug discussion forums) and medical literature (PubMed and abstracts from selected International Toxicology conferences). Results. We found 48 unrelated Internet suppliers selling phenibut in amounts ranging from 5 g (US$1.60, £1.01/g) to 1000 kg (US$0.23, £0.14/g). Capsules containing 200–500 mg of phenibut were available in packs of between 6 (US$4.45, £2.80/g) and 360 (US$0.43, £0.27/g). According to the grey literature, phenibut is taken for its anxiolytic and euphoric properties, with tolerance and withdrawal syndromes commonly reported adverse effects. Phenibut is taken orally at an average dose of 2.4 g. Case reports in the medical literature feature users who present to emergency departments heavily sedated or experiencing with- drawal.Therehavebeennoreporteddeathsrelating tophenibutuse. DiscussionandConclusions. Phenibut is readily available in the UK from Internet sites selling NPS. Its desired and adverse effects appear similar to other gamma-aminobutyric acid receptor agonists. [Owen DR, Wood DM, Archer JRH, Dargan PI. Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects and acute toxicity. Drug Alcohol Rev 2015;00:000–000] Key words: phenibut, GABA, GABAB, availability, recreational drug, NPS, acute toxicity, prevalence of use. Introduction Sweden, notified to the EMCDDA Early Warning System in 2012 [14]. There has been a global increase in the availability and Phenibut is available in its racemic form, but the use of novel psychoactive substances (NPS) over the last GABAB activity is conferred by the R-enantiomer. decade [1–7]. In Europe, there were 101 new NPS re- R-phenibut has a 10- to 15-fold lower affinity for the ported to the European Monitoring Centre for Drugs GABAB receptor than the structurally similar baclofen and Drug Addiction (EMCDDA) through its Early (Kd 25–90 vs 2.5–6 μM). Although its desired effects Warning System in 2014 [8]. (euphoria and anxiolysis) are thought to be mediated Phenibut (4-amino-3-phenyl-butyric acid) is an ana- primarily via GABAB receptors, phenibut also has ac- logue of gamma-aminobutyric acid (GABA) and a tivity at GABAA and dopamine receptors [10]. GABAB agonist [10], licenced in Russia for treatment There is limited information on the prevalence of use, of anxiety, alcohol withdrawal, stammering and insom- desired effects and acute toxicity of phenibut. Previous nia [10]. It is also used in preclinical experiments to in- studies have demonstrated that it is possible to obtain this fi ‘ ’ vestigate the effect of GABAB engagement in animal information from a range of both scienti cand grey lit- models [11–13]. Phenibut is not licenced within the erature, in a process known as data triangulation European Union, Australia or the USA. The first detection [2–4,15]. The aim of this paper was to use this data of phenibut as an NPS in Europe was in a 2011 seizure in triangulation methodology for phenibut. David R. Owen MD, PhD, David M. Wood BSc (Hons), MB ChB (Hons), MD, FRCP, FEAPCCT, FBPhS, FACMT, Consultant Physician and Clinical Toxicologist and Service (Clinical) Lead for Medicine, Honorary Senior Lecturer, John R.H. Archer Consultant Physician & Clinical Toxicologist, Paul I. Dargan MBBS FRCPE FACMT FRCP ERT FAACT FBPhS FEAPCCT. Correspondence to Dr Paul Dargan, Clinical Toxicology, Third Floor, Block C, South Wing, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UK. Tel: +442071885848; E-mail: [email protected] Received 21 June 2015; accepted for publication 22 September 2015. © 2015 Australasian Professional Society on Alcohol and other Drugs D. R. Owen et al. Methods containing 200–500 mg in packs of between 6 and 360. The mean price of phenibut powder was US$0.41 (£0.27) Phenibut availability survey per gram from suppliers in the USA and £0.39 (US$0.59) Using the EMCDDA Internet snapshot methodology per gram from suppliers in the UK. The capsules were [16], we undertook an Internet snapshot survey in English more than double the price, at US$0.99 (£0.65) per gram using the searchengines‘google.co.uk’, ‘yahoo.co.uk’ and from suppliers in the USA and £0.87 (US$1.32) per gram ‘metacrawler.com’ in May 2015, using search terms ‘buy from suppliers in the UK. The cost per gram of the powder phenibut’ and ‘buy fenibut’ and ‘buy 4-amino-3-phenyl- was cheaper when it was sold in larger amounts. From UK butyric acid’.Thefirst 100 sites identified were reviewed suppliers, the cost of phenibut was £1.16/g for 10 g, before continuing the searches to exhaustion. Data were £0.46/g for 25 g, £0.30/g for 100 g, £0.23/g for 1 kg and extracted from each individual site only once, irrespective £0.15/g for 1000 kg. From US suppliers, the cost was US of search term. Sites that appeared unable to ship products $1.05/g (£0.68/g) for 10 g, US$0.58/g (£0.38/g) for 25 g, toEuropewereexcluded,asperEMCDDAmethodology. US$0.31/g (£0.20/g) for 100 g and US$0.18/g (£0.12/g) Data were extracted from these Internet sites on the for1kg.Thepricepergramwasalsolowerwhencapsules amount (mass quantity of powder and number and size were purchased in increasing amounts: 60 capsules were of capsules) of phenibut available and cost and converted US$1.92/g (£1.24/g), 180 capsules were US$0.44/g into cost per gram. Additionally, we extracted the appar- (£0.28/g) and 360 capsules were US$0.41/g (£0.27/g). ent country of origin of the Internet site. User reports Grey information sources From the six Internet forums that were searched, six Using the keywords ‘phenibut’, ‘fenibut’ and ‘4-amino-3- contained reports that met the inclusion criteria. In total, phenyl-butyric acid’, the Internet search engine Google. 105 reports were found, 45 from www.bluelight.org/vb/ co.ukandonlinedrugdiscussionforumsErowid,Drugs content [17], 21 from www.erowid.org [18], 20 from Forum, Bluelight, UK Chemical Research, Grind Fac- www.ukchemicalresearch.org [19], 15 from www.drugs- tor and Personal Power Meditation were searched in forum.com [20], 3 from www.grindfactor.com [21] and May 2015. Relevant information relating to the preva- 1 from www.personalpowermeditation.com [22]. lence of use, desired effects and/or adverse effects was extracted from entries where both a dose and a route of phenibut administration were stated. This information Administration fi was then collated to extract relevant themes identi ed Of the 105 user reports, all but four reported oral admin- through qualitative review. istration of phenibut by direct swallowing. Of the remain- ing four, one user reported nasal insufflation of phenibut powder, and three reported rectal administration of Published scientific literature phenibut powder. Nasal insufflation was described as PubMed was searched in English using the keywords very painful, causing the nostrils to swell [23]. ‘phenibut’, ‘fenibut’ and ‘4-amino-3-phenyl-butyric acid’ Therewaswidevariationinthesingleoraldosesthatwere for articles that reported on availability, prevalence of use reported. The mean ± standard deviation dose reported or desired and adverse effects associated with recreational was 2.43 ± 1.62 g. The lowest dose reported was 500 mg phenibut use. Abstracts from selected international toxi- (in 3/105 cases), and at this dose, desired effects were still cology conferences (European Association of Poisons apparent. The highest dose reported was 9 g (2/105 cases). Centres and Clinical Toxicologists and North American The onset of desired effects was reported to occur Congress of Clinical Toxicology) from 2002 to 2015 2–4 h following oral ingestion and 20–30 min after rectal were searched using the same keywords. administration, peaking within 4–6h andwithanoverall duration of 15–24 h. Because of this long latency, first- time users often reported taking a repeat dose believing Results that the initial dose had not worked [24]. Phenibut availability Desired effects Forty-eight unrelated Internet suppliers selling phenibut were identified, either direct from the UK (17) or to be The two most commonly reported desired effects were shipped to the UK from USA (25), China (3), Australia disappearance of social anxiety (36/105) and a sense of (2) or Canada (1). Phenibut was available as a powder euphoria (34/105). Users reported the former as mak- in amounts ranging from 5 g to 1000 kg and as capsules ing them more talkative and socially confident [24]. © 2015 Australasian Professional Society on Alcohol and other Drugs Phenibut and acute toxicity Indeed, self-medication for social anxiety, distinct from 7 weeks, which was then weaned over 24 weeks [29].
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