Skip to main content Accessibility help
×
Hostname: page-component-848d4c4894-pjpqr Total loading time: 0 Render date: 2024-06-19T15:01:45.541Z Has data issue: false hasContentIssue false

Part II - Drugs with Primarily Depressant Effects

Published online by Cambridge University Press:  06 October 2022

Dima Abdulrahim
Affiliation:
Programme Manager and Principal Researcher for the NEPTUNE Project, Central and North West London NHS Foundation Trust
Owen Bowden-Jones
Affiliation:
Consultant Addiction Psychiatrist, Central and North West London NHS Foundation Trust
Get access

Summary

Image of the first page of this content. For PDF version, please use the ‘Save PDF’ preceeding this image.'
Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

Busardò, FP, Gottardi, M, Tini, A, et al. Replacing GHB with GBL in recreational settings: a new trend in chemsex. Curr Drug Metab 2018;19(13):10801085https://doi.org/10.2174/1389200219666180925090834Google Scholar
See for example Castro AL, , Dias AS, Melo P, Tarelho S, , Franco JM, , Teixeira HM., Quantification of GHB and GHB-GLUC in an 1,4-butanediol intoxication: a case report. Forensic Sci Int 2019;297:378382. https://doi.org/10.1016/j.forsciint.2019.01.035Google Scholar
Stefani M, , Roberts DM., 1,4-Butanediol overdose mimicking toxic alcohol exposure. Clin Toxicol 2020;58(3):204207https://doi.org/10.1080/15563650.2019.1617419CrossRefGoogle ScholarPubMed
Office for National Statistics. Deaths Related to Drug Poisoning in England and Wales, 2013 (Statistical Bulletin). Home Office, September 2014.Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). GBL and 1,4-BD: Assessment of Risk to the Individual and Communities in the UK. Published 2008.Google Scholar
Palatini, P, Tedeschi, L, Frison, G, Padrini, R, Zordan, R, Orlando, R, et al. Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers. Eur J Clin Pharmacol 1993;45:353356.Google Scholar
Borgen, LA, Okerholm, R, Morrison, D, Lai, A. The influence of gender and food on the pharmacokinetics of sodium oxybate oral solution in healthy subjects. J Clin Pharmacol 2003;43:5965.CrossRefGoogle ScholarPubMed
Brenneisen, R, Elsohly, MA, Murphy, TP, Passarelli, J, Russmann, S, Salamone, SJ, et al. Pharmacokinetics and excretion of gamma-hydroxybutyrate (GHB) in healthy subjects. J Anal Toxicol 2004;28:625630.Google Scholar
Helrich, M, Mcaslan, TC, Skolnik, S, Bessman, SP. Correlation of blood levels of 4-hydroxybutyrate with state of consciousness. Anesthesiology 1964;25:771775.Google Scholar
Abanades, S, Farre, M, Segura, M, Pichini, S, Barral, D, Pacifici, R, et al. Gamma-hydroxybutyrate (GHB) in humans: pharmacodynamics and pharmacokinetics. Ann NY Acad Sci 2006;1074:559576.Google Scholar
Brailsford, AD, Cowan, DA, Kicman, AT. Pharmacokinetic properties of g-hydroxybutyrate (GHB) in whole blood, serum, and urine. J Anal Toxicol 2012;36(2):8895. https://doi.org/10.1093/jat/bkr023Google Scholar
Schep, LJ, Knudsen, K, Slaughter, RJ, Vale, JA, Mégarbane, B. The clinical toxicology of γ-hydroxybutyrate, γ-butyrolactone and 1,4-butanediol. Clin Toxicol 2012;50(6):458470. https://doi.org/10.3109/15563650.2012.702218Google Scholar
González, A, Nutt, D. Gamma hydroxy butyrate abuse and dependency. J Psychopharmacol. 200;519(2):195–204.CrossRefGoogle Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Report on the Risk Assessment of GHB in the Framework of the Joint Action on New Synthetic Drugs. Published 2002.Google Scholar
Carter LP, , Chen W, Wu H, et al. Comparison of the behavioral effects of gamma-hydroxybutyric acid (GHB) and its 4-methyl-substituted analog, gamma-hydroxyvaleric acid (GHV). Drug Alcohol Depend 2005;78(1):9199.Google Scholar
Bessman, SP, Fishbein, WN. Gamma-hydroxybutyrate, a normal brain metabolite. Nature 1963;200:12071208.Google Scholar
Poldrugo, F, Snead, OC. 1,4-butanediol and ethanol compete for degradation in rat brain and liver in vitro. Alcohol 1986;3(6):367370.Google Scholar
Poldrugo, F, Snead, OC. 1,4-butanediol, gamma-hydroxybutyric acid and ethanol: relationships and interactions. Neuropharmacology 1984;23(1):109113.Google Scholar
Quang, LS, Desai, MC, Shannon, MW, Woolf, AD, Maher, TJ. 4-methylpyrazole decreases 1,4-butanediol toxicity by blocking its in vivo biotransformation to gamma-hydroxybutyric acid. Ann NY Acad Sci 2004;1025:528537.Google Scholar
Carter LP, , Chen W, Wu H, et al.Comparison of the behavioral effects of gamma-hydroxybutyric acid (GHB) and its 4-methyl-substituted analog, gamma-hydroxyvaleric acid (GHV). Drug Alcohol Depend 2005;78(1):9199.CrossRefGoogle ScholarPubMed
Dijkstra BAG, Kamal R, van Noorden MS, , de Haan H, , Loonen AJM, De Jong CAJ., Detoxification with titration and tapering in gamma-hydroxybutyrate (GHB) dependent patients: The Dutch GHB monitor project. Drug Alcohol Depend (online) 2017:170164170173. https://doi.org/10.1016/j.drugalcdep.2016.11.014CrossRefGoogle Scholar
Xu X-M, , Wei Y-D, , Liu Y, , Li Z-X., Gamma-hydroxybutyrate (GHB) for narcolepsy in adults: an updated systematic review and meta-analysis. Sleep Med 2019;64: 6270. https://doi.org/10.1016/j.sleep.2019.06.017Google Scholar
Craig, K, Gomez HF, McManus JL, Bania TC. Severe gamma-hydroxybutyrate withdrawal: a case report and literature review. J Emerg Med 2000;18:6570.Google Scholar
Nicholson, KL, Balster, RL. GHB: a new and novel drug of abuse. Drug Alcohol Depend 2001;63:122.Google Scholar
Grela A, , Gautam L, , Cole MD., A multifactorial critical appraisal of substances found in drug-facilitated sexual assault cases. Forensic Sci Int 2018;292:5060. https://doi.org/10.1016/j.forsciint.2018.08.034Google Scholar
Bertol E, , Di Milia MG, , Fioravanti A, et al. Proactive drugs in DFSA cases: toxicological findings in an eight-years study. Forensic Sci Int 2018;291:207215.Google Scholar
Busardò FP, , Varì MR, , Di Trana A, , Malaca S, , Carlier J, , Di Luca NM., Drug-facilitated sexual assaults (DFSA): a serious underestimated issue. Eur Rev Med Pharmacol Sci 2019;23:1057710587.Google Scholar
Pettigrew, M. Somnophilia and sexual abuse through the administration of GHB and GBL. J Forensic Sci 2019;64(1):302303. https://doi.org/10.1111/1556-4029.13812Google Scholar
Paul, A, Mahesan, A. Date rape drugs in Las Vegas: detection after the fact. Obstet Gynecol 2019;133:98S. https://doi.org/10.1097/01.AOG.0000558790.02961.d9CrossRefGoogle Scholar
Varela M, , Nogue S, , Oro M., Gamma hydroxybutyrate use for sexual assault. Miro Emerg Med J 2004;21:255256. https://doi.org/10.1136/emj.2002.002402Google Scholar
Kapitány-Fövény M, , Zacher G, , Posta J, , Demetrovics Z., GH B-involved crimes among intoxicated patients. Forensic Sci Int 2017;275:2329. https://doi.org/10.1016/j.forsciint.2017.02.028Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). GHB and Its Precursor GBL: An Emerging Trend Case Study (Thematic Paper). Published 2008. Available at: www.emcdda.europa.eu/system/files/publications/505/TP_GHB_and_GBL_107300.pdf [last accessed 19 February 2022].Google Scholar
van Noorden, MS, Mol, T, Wisselink, J, Kuipers, W, Dijkstra, BAG. Treatment consumption and treatment re-enrollment in GHB-dependent patients in the Netherlands. Drug Alcohol Depend 2017;176:96101.Google Scholar
Kamal, RM, van Noorden, MS, Wannet, W, Beurmanjer, H, Dijkstra, BA, Schellekens, A. Pharmacological treatment in γ-hydroxybutyrate (GHB) and γ-butyrolactone (GBL) dependence: detoxification and relapse prevention. CNS Drugs 2017;31(1):5164.Google Scholar
Heliodore, C, Malissin, I, Megarbane, B, Gourlain, H, Labat, L. Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) poisonings admitted to the ICU: features and usefulness of plasma GHB concentration measurement. Clin Toxicol 2019;57(6);472. https://doi.org/10.1080/15563650.2019.1598646.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2019: Trends and Developments. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2019: Trends and Developments. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
Miró, Ò, Galicia, M, Dargan, P, et al. Intoxication by gamma hydroxybutyrate and related analogues: clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse. Toxicol Lett 2017;277:8491. https://doi.org/10.1016/j.toxlet.2017.05.030Google Scholar
Sumnall, H, Woolfalla, K, Edward, S, Cole, J, Beynon, C. Use, function, and subjective experiences of gammahydroxybutyrate (GHB). Drug Alcohol Depend 2008;92(1–3):286290.Google Scholar
Degenhardt, L, Darke, S, Dillon, P. GHB use among Australians: characteristics, use patterns and associated harm. Drug Alcohol Depend 2002;67(1):8994.Google Scholar
Guasp A. Gay and Bisexual Men’s Health Survey. Stonewall 2012.Google Scholar
Wood, DM, Measham, F, Dargan, PI. ‘Our favourite drug’: prevalence of use and preference for mephedrone in the London night-time economy 1 year after control. J Substance Use 2012;17(2):9197. https://doi.org/10.3109/14659891.2012.661025Google Scholar
Measham, F, Wood, DM, Dargan, PI, Moore, KA. The rise of legal highs: prevalence and patterns in the use of illegal drugs and first- and second-generation ‘legal highs’ in south London gay dance clubs. J Substance Use 2011;16(40):263272.CrossRefGoogle Scholar
Halkitis, PN, Palamar, JJ. GHB use among gay and bisexual men. Addict Behav 2006;31:21352139.Google Scholar
Giorgetti R, , Tagliabracci A, , Schifano F, , Zaami S, , Marinelli E, , Busardò FP., When ‘chems’ meet sex: a rising phenomenon called ‘chemsex’. Curr Neuropharmacol 2017;15(5): 762770.Google Scholar
Hibbert, MP, Brett, CE, Porcellato, LA, Hope, VD. Psychosocial and sexual characteristics associated with sexualised drug use and chemsex among men who have sex with men (MSM) in the UK. Sex Transm Infect 2019;95(5):13684973.Google Scholar
Trombley TA, , Capstick RA, , Lindsle CW., DARK classics in chemical neuroscience: gamma-hydroxybutyrate (GHB). ACS Chem Neurosci 2019 (online). https://doi.org/10.1021/acschemneuro.9b00336Google Scholar
Hammoud, MA, Bourne, A, Maher, L, et al. Intensive sex partying with gamma-hydroxybutyrate: factors associated with using gamma-hydroxybutyrate for chemsex among Australian gay and bisexual men – results from the Flux Study. Sex Health 2018;15(2):123134. https://doi.org/10.1071/SH17146CrossRefGoogle ScholarPubMed
Joyce N, , MacNeela P, , Sarma K, , Ryall G, , Keenan E., The experience and meaning of problematic ‘G’ (GHB/GBL) use in an Irish context: an interpretative phenomenological analysis. Int J Ment Health Addict 2018;16:10331054. https://doi.org/10.1007/s11469-017-9851-yGoogle Scholar
Giorgetti, R, Tagliabracci, A, Schifano, F, Zaami, S, Marinelli, E, Busardò, FP. When chems meet sex: a rising phenomenon called ChemSex. Curr Neuropharmacol 2017;15(5):762770.Google Scholar
Bell, J, Gamma-butyrolactone, Collins R. (GBL) dependence and withdrawal. Addiction 2011;106(2):442447. https://doi.org/10.1111/j.1360-0443.2010.03145.xGoogle Scholar
Grund J-P, , de Bruin D, , Van Gallen S., Going knock: recurrent comatose GHB intoxication in the Netherlands. Int J Drug Policy 2018;58:137148.Google Scholar
Evans, R, Sayal, K. Gammabutyrolactone: withdrawal syndrome resembling delirium tremens. J Substance Use 2012;17(4):384387.Google Scholar
Miotto, K, Darakjian, J, Basch, J, Murray, S, Zogg, J, Rawson, R. Gamma-hydroxybutyric acid: patterns of use, effects and withdrawal. Am J Addict 2001;10(3):232241.Google Scholar
de Jong, CA, Kamal, R, Dijkstra, BA, de Haan, HA. Gamma-hydroxybutyrate detoxification by titration and tapering. Eur Addict Res 2012;18(1):4045. https://doi.org/10.1159/000333022Google Scholar
Herold, AH, Sneed, KB. Treatment of a young adult taking gamma-butyrolactone (GBL) in a primary care clinic. J Am Board Fam Pract 2002;15(2):161163.Google Scholar
Drug Enforcement Agency.Google Scholar
Couper, FJ, Marinetti, LJ. Gamma-hydroxybutyrate (GHB) – effects on human performance and behavior. Forensic Sci Rev 2002;14(1):101121.Google Scholar
McDonough, M, Kennedy, N, Glasper, A, Bearn, J. Clinical features and management of gamma- hydroxybutyrate (GHB) withdrawal: a review. Drug Alcohol Depend 2004; 75:39.Google Scholar
Chew, G, Fernando, A. Epileptic seizure in GHB withdrawal. Australas Psychiatry 2004;12:410411.Google Scholar
Sivilotti, MLA, Burns, MJ, Aaron, CK, Greenberg, MJ. Pentobarbital for severe gamma-butyrolactone withdrawal. Ann Emerg Med 2001;38:660665.Google Scholar
Kam, P, Yoong, F. Gamma-hydroxybutyric acid: an emerging recreational drug. Anaesthesia 1998;53:11951198.Google Scholar
Abanades, S, Farré, M, Barral, D, Torrens, M, Closas, N, Langohr, K, et al. Relative abuse liability of [gamma]-hydroxybutyric acid, flunitrazepam, and ethanol in club drug users. J Clin Psychopharmacol 2007;27(6):625638.Google Scholar
Galicia, M, Nogue, S, Miro, O. Liquid ecstasy intoxication: clinical features of 505 consecutive emergency department patients. Emerg Med J 2011;28(6):462466. https://doi.org/10.1136/emj.2008.068403Google Scholar
Luby, S, Jones, J, Zalewski, A. GHB use in South Carolina. Am J Public Health 1992;82(1):128.Google Scholar
Henderson, DL, Ginsberg, JP. Withdrawal, recovery, and long-term sequelae of gamma- butyrolactone dependence: a case report. Am J Addict 2008;17(5):456457. https://doi.org/10.1080/10550490802266193Google Scholar
Zvosec, DL, Smith, SW. Agitation is common in gamma-hydroxybutyrate toxicity. Am J Emerg Med 2005;23(3):316320.Google Scholar
Oliveto, A, Gentry, WB, Pruzinsky, R, et al. Behavioral effects of gamma-hydroxybutyrate in humans. Behav Pharmacol 2010;21(4):332342. https://doi.org/10.1097/FBP.0b013e32833b3397Google Scholar
Stein, LA, Lebeau, R, Clair, M, et al. A web-based study of gamma hydroxybutyrate (GHB): patterns, experiences, and functions of use. Am J Addict 2011;20(1):3039. https://doi.org/10.1111/j.1521-0391.2010.00099.xGoogle Scholar
Kapitány-Fövény M, , Mervó B, , Corazza O, et al. Enhancing sexual desire and experience: an investigation of the sexual correlates of gamma-hydroxybutyrate (GHB). Hum Psychopharmacol Clin Exp 2015;30:276284. https://doi.org/10.1002/hup.2491Google Scholar
Bourne, A, Reid, D, Hickson, F, Torres-Rueda, S, Weatherburn, P. Illicit drug use in sexual settings (‘chemsex’) and HIV/STI transmission risk behaviour among gay men in South London: findings from a qualitative study. Sex Transm Infect (online). https://doi.org/10.1136/sextrans-2015-052052Google Scholar
Daskalopoulou, M, Rodger, A, Thornton, A, et al. Sexual behaviour, recreational drug use and hepatitis C co-infection in HIV-diagnosed men who have sex with men in the United Kingdom: results from the ASTRA study. J Int AIDS Soc 2014b;17(4 Suppl. 3). https://doi.org/10.7448/IAS.17.4.19630Google Scholar
Colfax, GN, Mansergh, G, Guzman, R, et al. Drug use and sexual risk behaviour among gay and bisexual men who attend circuit parties: a venue-based comparison. J Acquir Immune Defic Syndr 2001;28(4):373379.Google Scholar
Mattison, AM, Ross, MW, Wolfson, T, Franklin, D, San Diego HIV Neurobehavioral Research Center Group. Circuit party attendance, club drug use and unsafe sex in gay men. J Subst Abuse 2001;13(1–2):119126.Google Scholar
Keogh, P, Reid, D, Bourne, A, et al. Wasted Opportunities: Problematic Alcohol and Drug Use Among Gay Men and Bisexual Men. Sigma Research, 2009. Available at: http://sigmaresearch.org.uk/files/report2009c.pdf [last accessed 19 February 2022].Google Scholar
Hammoud, MA, Bourne, A, Maher, L, et al. Intensive sex partying with gamma-hydroxybutyrate: factors associated with using gamma-hydroxybutyrate for chemsex among Australian gay and bisexual men – results from the Flux Study. Sex Health 2018;15(2):123134. https://doi.org/10.1071/SH17146Google Scholar
Bourne A, , Ong, J, Pakianathan, M. Sharing solutions for a reasoned and evidence-based response: chemsex/party and play among gay and bisexual men. Sex Health 2018;15:99101. https://doi.org/10.1071/SH18023Google Scholar
O’Reilly M., Chemsex case study: is it time to recommend routine screening of sexualised drug use in men who have sex with men? Sex Health 2018;15(2):167169. https://doi.org/10.1071/SH17156Google Scholar
Bourne A, Reid D, Hickson F, Torres-Rueda S, Weatherburn P. Illicit drug use in sexual settings (‘chemsex’) and HIV/STI transmission risk behaviour among gay men in South London: findings from a qualitative study. Sex Transm Infect 2015;91(8):564–568.Google Scholar
Advisory Council on the Misuse of Drugs: An assessment of the harms of gamma-hydroxybutyric acid (GHB), gamma-butyrolactone (GBL), and closely related compounds. Published 2020.Google Scholar
Schep, LJ, Knudsen, K, Slaughter, RJ, Vale, JA, Mégarbane, B. The clinical toxicology of γ-hydroxybutyrate, γ-butyrolactone and 1,4-butanediol. Clin Toxicol 2012;50(6):458470. https://doi.org/10.3109/15563650.2012.702218Google Scholar
Caldicott, DG, Chow, FY, Burns, BJ, Felgate, PD, Byard, RW. Fatalities associated with the use of gamma-hydroxybutyrate and its analogues in Australasia. Med J Aust 2004;181:310313.Google Scholar
Couper, FJ, Thatcher, JE, Logan, BK. Suspected GHB overdoses in the emergency department. J Anal Toxicol 2004;28:481484.Google Scholar
Corkery, JM, Loi, B, Claridge, H, et al. Gamma hydroxybutyrate (GHB), gamma butyrolactone (GBL) and 1,4 butanediol (1,4-BD; BDO): a literature review with a focus on UK fatalities related to non-medical use. Neurosci Biobehav Rev 2015 (online). http://dx.doi.org/10.1016/j.neubiorev.2015.03.012Google Scholar
Küting, T, Krämer, M, Bicker, W, Madea, B, Hess, C. Case report: another death associated to γ-hydroxybutyric acid intoxication. Forensic Sci Int 2019;299:3440.Google Scholar
Corkery, JM, Loi, B, Claridge, H, et al. Gamma hydroxybutyrate (GHB), gamma butyrolactone (GBL) and 1,4 butanediol (1,4-BD; BDO): a literature review with a focus on UK fatalities related to non-medical use. Neurosci Biobehav Rev (online) 2015. https://doi.org/10.1016/j.neubiorev.2015.03.012Google Scholar
National Programme on Substance Abuse Deaths (NPSAD). Drug-Related Deaths Reported by Coroners in England, Wales, Northern Ireland, Guernsey, Jersey and the Isle of Man; Police Forces in Scotland; and the Northern Ireland Statistics and Research Agency Annual Report 2013 on Deaths Between January–December 2012.Google Scholar
Darke S, , Peacock A, , Duflou J, , Farrell M, , Lappin J., Characteristics and circumstances of death related to gamma hydroxybutyrate (GHB). Clin Toxicol 2020 (online). https://doi.org/10.1080/15563650.2020.1726378Google Scholar
Hockenhulla J, , Murphy KG, , Paterson S. An observed rise in g-hydroxybutyrate-associated deaths in London: evidence to suggest a possible link with concomitant rise in chemsex. Forensic Sci Int 2017;270:9397.Google Scholar
Corkery, JM, Loi, B, Claridge, H, Goodair, C, Schifano, F. Deaths in the lesbian, gay, bisexual and transgender United Kingdom communities associated with GHB and precursors. Curr Drug Metab 2017 (online). https://doi.org/10.2174/1389200218666171108163817Google Scholar
Chin, RL, Sporer, KA, Cullison, B, Dyer, JE, Wu, TD. Clinical course of gamma-hydroxybutyrate overdose. Ann Emerg Med 1998;31(6):716722.Google Scholar
Miróa O, , Galiciaa M, , Darganb P, et al. Euro-DEN Research Group: Intoxication by gamma hydroxybutyrate and related analogues: clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse. Toxicol Lett 2017;277(5):8491. https://doi.org/10.1016/j.toxlet.2017.05.030Google Scholar
Morse BL, , Chadha GS, , Felmlee MA, , Follman KE, , Morris ME., Effect of chronic γ-hydroxybutyrate (GHB) administration on GHB toxicokinetics and GHB-induced respiratory depression. Am J Drug Alcohol Abuse 2017;43(6):686693. https://doi.org/10.1080/00952990.2017.1339055Google Scholar
Gable, RS. Acute toxic effects of club drugs. J Psychoactive Drugs 2004;36(3):303313.Google Scholar
Snead, OC, Gibson, KM. Gamma-hydroxybutyric acid. N Engl J Med 2005;352(26):27212732.Google Scholar
Li, J, Stokes, SA, Woeckener, A. A tale of novel intoxication: a review of the effects of gamma-hydroxybutyric acid with recommendations for management. Ann Emerg Med 1998;31:729736.Google Scholar
Centers for Disease Control (CDC). Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. Morb Mortal Wkly Rep 1990;39:861863.Google Scholar
Vickers, MD. Gamma-hydroxybutyric acid. Int Anesthesiol Clin 1969;7:7589.CrossRefGoogle Scholar
Galloway, GP, Frederick, SL, Staggers, FE, et al. Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence. Addiction 1997;92:8996.Google Scholar
Grund JP, , de Bruin D, , van Gaalen S., Going knock: recurrent comatose GHB intoxication in the Netherlands. Int J Drug Policy 2018;58:137148. https://doi.org/10.1016/j.drugpo.2018.06.010Google Scholar
Madah-Amiri D, , Myrmel L, , Brattebø G., Intoxication with GHB/GBL: characteristics and trends from ambulance-attended overdoses. Scand J Trauma Resusc Emerg Med 2017;25:98. https://doi.org/10.1186/s13049-017-0441-6Google Scholar
Schep, LJ, Knudsen K, Slaughter RJ, Vale JA, Mégarbane B. The clinical toxicology of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4-butanediol. Clin Toxicol (Phila) 2012;50:458470.Google Scholar
Korf, DJ, Nabben, T, Benschop, A, Ribbink, K, Van Amsterdam, JGC. Risk factors of γ-hydroxybutyrate overdosing. Eur Addict Res 2014;20:6674.Google Scholar
Liechti, ME, Kunz, I, Greminger, P, Speich, R, Kupferschmidt, H. Clinical features of gamma-hydroxybutyrate and gamma-butyrolactone toxicity and concomitant drug and alcohol use. Drug Alcohol Depend 2006;81:323326.Google Scholar
Miró, Ò, Galicia, M, Dargan, P, et al. Intoxication by gamma hydroxybutyrate and related analogues: clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse. Toxicol Lett 2017;277:8491.Google Scholar
Van Amsterdam, JGC, Brunt, TM, McMaster, MTB, Niesink, RJM. Possible long-term effects of γ-hydroxybutyric acid (GHB) due to neurotoxicity and overdose. Neurosci Biobehav Rev 2012;36:12171227.Google Scholar
Kapitány-Fövény M, , Mervó B, , Corazza O, et al. Enhancing sexual desire and experience: an investigation of the sexual correlates of gamma-hydroxybutyrate (GHB) use. Hum Psychopharmacol Clin Exp 2015;30:276284. https://doi.org/10.1002/hup.2491Google Scholar
Nunez OF, Lopez, Rymer JA, , Tamama K, , Case of sudden acute coma followed by spontaneous recovery. J Appl Lab Med 2018;3(3):507510https://doi.org/10.1373/jalm.2017.025718Google Scholar
Korf, DJ, Nabben, T, Benschop, A, Ribbink, K, Van Amsterdam, JGC. Risk factors of γ-hydroxybutyrate overdosing. Eur Addict Res 2014;20:6674.Google Scholar
Liechti, ME, Kunz, I, Greminger, P, Speich, R, Kupferschmidt, H. Clinical features of gamma-hydroxybutyrate and gamma-butyrolactone toxicity and concomitant drug and alcohol use. Drug Alcohol Depend 2006;81:323326.Google Scholar
Miró, Ò, Galicia, M, Dargan, P, et al. Intoxication by gamma-hydroxybutyrate and related analogues: clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse. Toxicol Lett 2017;277:8491.Google Scholar
Miró, O, Nogué, S, Espinosa, G, To-Figueras, J, Sánchez, M. Trends in illicit drug emergencies: the emerging role of gamma-hydroxybutyrate. J Toxicol Clin Toxicol 2002;40(2):129135.Google Scholar
Louagie, HK, Verstraete, AG, DeSoete, CJ, Baetens, DG, Calle, PA. A sudden awakening from a near coma after combined intake of gamma-hydroxybutyric acid (GHB) and ethanol. J Toxicol Clin Toxicol 1997;35:591594.Google Scholar
Ingels, M, Rangan, C, Bellezzo, J, Clark, RF. Coma and respiratory depression following the ingestion of GHB and its precursors: three cases. J Emerg Med 2000;9(1):4750.Google Scholar
Munir, VL, Hutton, JE, Harney, JP, Buykx, P, Weiland, TJ, Dent, AW. Gamma-hydroxybutyrate: a 30-month emergency department review. Emerg Med Australas 2008;20(6):521530. https://doi.org/10.1111/j.1742- 6723.2008.01140.x.Google Scholar
Van Sassenbroeck, DK, De Neve, N, De Paepe, P, Belpaire, FM, Verstraete, AG, Calle, PA, et al. Abrupt awakening phenomenon associated with gamma-hydroxybutyrate use: a case series. Clin Toxicol 2007;45:533538.Google Scholar
Liakoni E, , Walther F, , Nickel CH, , Liechti ME, . Presentations to an urban emergency department in Switzerland due to acute γ-hydroxybutyrate toxicity. Scand J Trauma Resusc Emerg Med 2016;24:107. https://doi.org/10.1186/s13049-016-0299-zGoogle Scholar
Madah-Amiri, D, Myrmel L, Brattebø G. Intoxication with GHB/GBL: characteristics and trends from ambulance-attended overdoses. Scand J Trauma Resusc Emerg Med 2017;25:98. https://doi.org/10.1186/s13049-017-0441-6Google Scholar
Madah‐Amiri D, Clausen T, Myrmel L, Brattebø G, Lobmaier P. Circumstances surrounding non-fatal opioid overdoses attended by ambulance services. Drug Alcohol Rev 2017;36:288294.Google Scholar
CarlierL, Van Belleghem, V, Croes, K, Hooft, F. Gamma-hydroxybutyrate (GHB), an unusual cause of high anion gap metabolic acidosis. Can J Emerg Med 2018;20(S2):S2S5.Google Scholar
Stefani M, , Roberts DM., 1,4-Butanediol overdose mimicking toxic alcohol exposure. Clin Toxicol 2020;58(3):204207https://doi.org/10.1080/15563650.2019.1617419Google Scholar
Wood, DM, Warren-Gash, C, Ashraf, T, et al. Medical and legal confusion surrounding gamma-hydroxybutyrate (GHB) and its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD). QJM 2008;101:2329.Google Scholar
Rambourg-Schepens, MO, Buffet, M, Durak, C, Mathieu-Nolf, M. Gamma-butyrolactone poisoning and its similarities to gamma-hydroxybutyric acid: two case reports. Vet Hum Toxicol 1997;39(4):234235.Google Scholar
Knudsen, K, Greter, J, Verdicchio, M. High mortality rates among GHB abusers in Western Sweden. Clin Toxicol 2008;46:187192.Google Scholar
Liechti, ME, Kunz, I, Greminger, P, Speich, R, Kupferschmidt, H. Clinical features of gamma-hydroxy-butyrate and gamma-butyrolactone toxicity and concomitant drug and alcohol use. Drug Alcohol Depend 2006;81:323326.Google Scholar
Dietze, PM, Cvetkovski, S, Barratt, MJ, Clemens, S. Patterns and incidence of gamma-hydroxybutyrate (GHB)-related ambulance attendances in Melbourne, Victoria. Med J Aust 2008;188:709711.Google Scholar
Theron, L, Jansen, K, New Zealand’s, Skinner A. first fatality linked to use of 1,4-butanediol (1,4-B, Fantasy): no evidence of coingestion or comorbidity. N Z Med J 2003;116:U650.Google Scholar
Couper, FJ, Thatcher, JE, Logan, BK. Suspected GHB overdoses in the emergency department. J Anal Toxicol 2004;28:481484.Google Scholar
Roberts, DM, Smith, MW, Gopalakrishnan, M, Whittaker, G, Day, RO. Extreme gamma-butyrolactone overdose with severe metabolic acidosis requiring hemodialysis. Ann Emerg Med 2011;58:8385.Google Scholar
Anderson, IB, Kim, SY, Dyer, JE, et al. Trends in gamma-hydroxybutyrate (GHB) and related drug intoxication: 1999 to 2003. Ann Emerg Med 2006;47:177183.Google Scholar
Ryan, JM, Stell, I. Gamma hydroxybutyrate: a coma inducing recreational drug. J Accid Emerg Med 1997;14:259291.Google Scholar
Centers for Disease Control and Prevention (CDC). Gamma hydroxy butyrate use – New York and Texas, 1995–1996. Morb Mortal Wkly Rep 1997;46:281283.Google Scholar
Schneidereit, T, Burkhart, K, Donovan, JW. Butanediol toxicity delayed by preingestion of ethanol. Int J Med Toxicol 2000;3:1.Google Scholar
Zvosec, DL, Smith, SW, McCutcheon, JR, Spillane, J, Hall, BJ, Peacock, EA. Adverse events, including death, associated with the use of 1,4-butanediol. N Engl J Med 2001;344:8794.Google Scholar
Centers for Disease Control and Prevention (CDC). Adverse events associated with ingestion of gamma-butyrolactone – Minnesota, New Mexico, and Texas, 1998–1999. Morb Mortal Wkly Rep 1999;48:137140.Google Scholar
Stephens, BG, Baselt, RC. Driving under the influence of GHB? J Anal Toxicol 1994;18:357358.Google Scholar
Al-Samarraie, MS, Karinen, R, Morland, J, Opdal, MS. Blood GHB concentrations and results of medical examinations in 25 car drivers in Norway. Eur J Clin Pharmacol 2010;66:987998.Google Scholar
Ross, TM. Gamma hydroxybutyrate overdose: two cases illustrate the unique aspects of this dangerous recreational drug. J Emerg Nurs 1995;21:374376.Google Scholar
Ortmann, LA, Jaeger, MW, James, LP, Schexnayder, SM. Coma in a 20-month-old child from an ingestion of a toy containing 1,4-butanediol, a precursor of gamma-hydroxybutyrate. Pediatr Emerg Care 2009;25:758760.Google Scholar
Price, PA, Schachter, M, Smith, S, Baxter, RC, Parkes, JD. Gamma-hydroxybutyrate in narcolepsy. Ann Neurol 1981;9:198.Google Scholar
Couper, FJ, Logan, BK. Determination of gamma-hydroxybutyrate (GHB) in biological specimens by gas chromatography–mass spectrometry. J Anal Toxicol 2000;24:17.Google Scholar
Eckstein, M, Henderson, SO, DelaCruz, P, Newton, E. Gamma hydroxybutyrate (GHB): report of a mass intoxication and review of the literature. Prehosp Emerg Care 1999;3:357361.Google Scholar
Bosman, IJ, Lusthof, KJ. Forensic cases involving the use of GHB in the Netherlands. Forensic Sci Int 2003;133:1721.Google Scholar
Mégarbane, B, Fompeydie, D, Garnier, R, Baud, FJ. Treatment of a 4-butanediol poisoning with fomepizole. J Toxicol Clin Toxicol 2002;40:7780.Google Scholar
Piastra, M, Tempera, A, Caresta, E, et al. Lung injury from ‘liquid ecstasy’: a role for coagulation activation? Pediatr Emerg Care 2006;22:358360.Google Scholar
Gunja, N, Doyle, E, Carpenter, K, et al. Gamma-hydroxybutyrate poisoning from toy beads. Med J Aust 2008;188:5455.Google Scholar
Hefele, B, Naumann, N, Trollmann, R, Dittrich, K, Rascher, W. Fast-in, fast-out. Lancet 2009;373:1398.Google Scholar
Ragg, M. Gamma hydroxy butyrate overdose. Emerg Med 1997;9:2931.Google Scholar
Williams, H, Taylor, R, Roberts, M. Gamma-hydroxybutyrate (GHB): a new drug of misuse. Ir Med J 1998;91:5657.Google Scholar
Dyer, JE. Gamma-hydroxybutyrate: a health-food product producing coma and seizure-like activity. Am J Emerg Med 1991;9:321324.Google Scholar
Chin, MY, Kreutzer, RA, Dyer, JE. Acute poisoning from gamma-hydroxybutyrate in California. West J Med 1992;156:380384.Google Scholar
Viswanathan, S, Chen, C, Kolecki, P. Revivarant (gamma-butyrolactone) poisoning. Am J Emerg Med 2000;18:358359.Google Scholar
Osterhoudt, KC, Henretig, FM. Comatose teenagers at a party: what a tangled ‘Web’ we weave. Pediatr Case Rev 2003;3:171173.Google Scholar
Shannon, M, Quang, LS. Gamma-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol: a case report and review of the literature. Pediatr Emerg Care 2000;16:435440.Google Scholar
Caldicott, DG, Kuhn, M. Gamma-hydroxybutyrate overdose and physostigmine: teaching new tricks to an old drug? Ann Emerg Med 2001;37:99102.Google Scholar
Runnacles, JL, Stroobant, J. Gamma-hydroxybutyrate poisoning: poisoning from toy beads. BMJ 2008;336:110.Google Scholar
Yates, SW, Viera, AJ. Physostigmine in the treatment of gamma-hydroxybutyric acid overdose. Mayo Clin Proc 2000;75:401402.Google Scholar
Libetta, C. Gamma hydroxybutyrate poisoning. J Accid Emerg Med 1997;14:411.Google Scholar
Savage, T, Khan, A, Loftus, BG. Acetone-free nail polish remover pads: toxicity in a 9-month-old. Arch Dis Child 2007;92:371.Google Scholar
Robert, R, Eugène, M, Frat, JP, Rouffineau, J. Diagnosis of unsuspected gamma hydroxy-butyrate poisoning by proton NMR. J Toxicol Clin Toxicol 2001;39:653654.Google Scholar
Winickoff, JP, Houck, CS, Rothman, EL, Bauchner, H. Verve and jolt: deadly new Internet drugs. Pediatrics 2000;106:829831.Google Scholar
Lenz, D, Rothschild, MA, Kroner, L. Intoxications due to ingestion of gamma-butyrolactone: organ distribution of gamma-hydroxybutyric acid and gamma-butyrolactone. Ther Drug Monit 2008;30:755761.Google Scholar
Lora-Tamayo, C, Tena, T, Rodriguez, A, Sancho, JR, Molina, E. Intoxication due to 1,4-butanediol. Forensic Sci Int 2003;133:256259.Google Scholar
Higgins, TFJ, Borron, SW. Coma and respiratory arrest after exposure to butyrolactone. J Emerg Med 1996;14:435457.Google Scholar
Yambo, CM, McFee, RB, Caraccio, TR, McGuigan, M. The inkjet cleaner ‘Hurricane’ – another GHB recipe. Vet Hum Toxicol 2004;46:329330.Google Scholar
Suner, S, Szlatenyi, CS, Wang, RY. Pediatric gamma hydroxybutyrate intoxication. Acad Emerg Med 1997;4:10411045.Google Scholar
Krul, J, Girbes, AR. Gamma-hydroxybutyrate: experience of 9 years of gamma-hydroxybutyrate (GHB)-related incidents during rave parties in the Netherlands. Clin Toxicol 2011;49:311315.Google Scholar
Elliott, S. Nonfatal instances of intoxication with gamma-hydroxybutyrate in the United Kingdom. Ther Drug Monit 2004;26:432440.Google Scholar
Tancredi, DN, Shannon, MW. Case records of the Massachusetts General Hospital. Weekly clinico-pathological exercises. Case 30-2003. A 21-year-old man with sudden alteration of mental status. N Engl J Med 2003;349:12671275.Google Scholar
Cisek, J. Seizure associated with butanediol ingestion. Int J Med Toxicol 2001;4:12.Google Scholar
Harraway, T, Stephenson, L. Gamma hydroxybutyrate intoxication: the Gold Coast experience. Emerg Med 1999;11:4548.Google Scholar
Hardy, CJ, Slifman, NR, Klontz, KC, Dyer, JE, Coody, GL, Love, LA. Adverse events reported with the use of gamma butyrolactone products marketed as dietary supplements. Clin Toxicol 1999;37:649650.Google Scholar
Mahon, KD, Tomaszewski, CA, Tayal, VS. Emergency department presentation of serum confirmed GHB ingestions. Acad Emerg Med 1999;6:395396.Google Scholar
Vickers, MD. Gamma hydroxybutyric acid. Proc R Soc Med 1968;61:821824.Google Scholar
Geldenhuys, FG, Sonnendecker, EW, De Kirk, MC. Experience with sodium-gamma-4-hydroxybutyric acid (gamma-OH) in obstetrics. J Obstet Gynaecol Br Commonw 1968;75(4):405413.Google Scholar
Tunstall, ME. Gamma-OH in anesthesia for caesarean section. Proc R Soc Med 1968;61:827830.Google Scholar
Laborit, H. Soduim 4-hydroxybutyrate. Int J Neuropharmacol 1964;3:433445.Google Scholar
Piastra, M, Barbaro, R, Chiaretti, A, Tempera, A, Pulitanò, S, Polidori, G. Pulmonary oedema caused by ‘liquid ecstasy’ ingestion. Arch Dis Child 2002;86:302303.Google Scholar
Jones, C. Suspicious death related to gamma-hydroxybutyrate (GHB) toxicity. J Clin Forensic Med 2001;8:7476.Google Scholar
Doyon, S. The many faces of ecstasy. Curr Opin Pediatr 2001;13(6):170176.Google Scholar
Bamonte, G, de Hoog, J, Van Den Biesen, PR. A case of central serous chorioretinopathy occurring after γ-hydroxybutyric acid (liquid ecstasy) ingestion. Retin Cases Brief Rep 2013;7(4):313314. https://doi.org/10.1097/ICB.0b013e31828ef073Google Scholar
Garrison, G, Mueller, P. Clinical features and outcomes after unintentional gamma hydroxybutyrate (GHB) overdose. J Toxicol Clin Toxicol 1998;35:503504.Google Scholar
Wood, DM, Brailsford, AD, Dargan, PI. Acute toxicity and withdrawal syndromes related to gamma-hydroxybutyrate (GHB) and its analogues gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD). Drug Test Anal 2011;3(7–8):417425. https://doi.org/10.1002/dta.292Google Scholar
Entholzner, E, Mielke, L, Pichlmeier, R, Weber, F, Schneck, H. EEG changes during sedation with gamma-hydroxybutyric acid. Anaesthesist 1995;44:345350.Google Scholar
Okun, MS, Boothby, LA, Bartfield, RB, Doering, PL. GHB: an important pharmacological and clinical update. J Pharm Pharm Sci 2001;4(2):167175.Google Scholar
Thai, D, Dyer, JE, Benowitz, NL, Haller, CA. Gamma-hydroxybutyrate and ethanol effects and interactions in humans. J Clin Psychopharmacol 2006;26(5):524529.Google Scholar
Department of Health. A Summary of the Health Harms of Drugs. Published August 2011.Google Scholar
Hammoud, MA, Bourne, A, Maher, L, et al. Intensive sex partying with gamma-hydroxybutyrate: factors associated with using gamma-hydroxybutyrate for chemsex among Australian gay and bisexual men – results from the Flux Study. Sex Health 2018;15(2):123134. https://doi.org/10.1071/SH17146Google Scholar
Lettieri, J, Fung, HL. Absorption and first-pass metabolism of 14C-gamma-hydroxybutyric acid. Res Commun Chem Pathol Pharmacol 1976;13:425437.Google Scholar
Harrington, RD, Woodward, JA, Hooton, TM, Horn, JR. Life-threatening interactions between HIV-1 protease inhibitors and the illicit drugs MDMA and gamma-hydroxybutyrate. Arch Intern Med 1999;159(18):22212224.Google Scholar
Harrington, RD, Woodward, JA, Hooton, TM, Horn, JR. Life-threatening interactions between HIV-1 protease inhibitors and the illicit drugs MDMA and gamma-hydroxybutyrate. Arch Intern Med 1999;159(18):22212224.Google Scholar
Romanelli, F, Smith, KM, Pomeroy, C. Use of club drugs by HIV-seropositive and HIV-seronegative gay and bisexual men. Top HIV Med 2003;11(1):2532.Google Scholar
Staltari, O, Leporini, C, Caroleo, B, et al. Drug-drug interactions: antiretroviral drugs and recreational drugs. Recent Pat CNS Drug Discov 2014;9:153163.Google Scholar
Psichogiou M, , Poulakou G, , Basoulis D, , Paraskevis D, , Markogiannakis A, , Daikos GL. Recent advances in antiretroviral agents: potent integrase inhibitors. Curr Pharmaceut Des 2017;23:116.Google Scholar
Drogies T, , Willenberg A, , Ramshorn-Zimmer, A, et al. Detection of gamma hydroxybutyrate in emergency department: nice to have or a valuable diagnostic tool? Hum Exp Toxicol 2015;35(7):18.Google Scholar
Busardò FP, , Jones AW., GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome. Curr Neuropharmacol 2015;13(1):4770.Google Scholar
LeTourneau, JL, Hagg, DS, Smith, SM. Baclofen and gamma-hydroxybutyrate withdrawal. Neurocrit Care 2008;8(3):430433. https://doi.org/10.1007/s12028-008-9062-2Google Scholar
LeTourneau, JL, Hagg, DS, Baclofen, Smith SM and gamma-hydroxybutyrate withdrawal. Neurocrit Care 2008;8(3):430433.Google Scholar
Mason, PE, Kerns, WP. Gamma hydroxybutyric acid (GHB) intoxication. Acad Emerg Med 2002;9(7):730739.Google Scholar
Busardò FP, , Jones AW., GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome. Curr Neuropharmacol 2015;13(1):4770.Google Scholar
Thomas, G, Bonner, S, Gascoigne, A. Coma induced by abuse of gamma-hydroxybutyrate (GHB or liquid ecstasy): a case report. BMJ 1997;314:3536.Google Scholar
Busardò FP, , Jones, AW. GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome. Curr Neuropharmacol 2015;13(1)4770.Google Scholar
Liechti, ME, Kupferschmidt, H. Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL): analysis of overdose cases reported to the Swiss Toxicological Information Centre. Swiss Med Wkly 2004;134:534537.Google Scholar
TOXBASE www.toxbase.org [accessed 3 February 2020].Google Scholar
TOXBASE www.toxbase.org [accessed 3 February 2020].Google Scholar
Busardò FP, , Jones AW., GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome. Curr Neuropharmacol 2015;13(1):4770.Google Scholar
TOXBASE www.toxbase.org [accessed 3 February 2020].Google Scholar
Follman, KE, Morris, M. Treatment of gamma-hydroxybutyric acid and gamma-butyrolactone overdose with two potent monocarboxylate transporter 1 inhibitors, AZD3965 and AR-C155858. J Pharmacol Exp Ther 2019;370(1);8491. https://doi.org/10.1124/jpet.119.256503Google Scholar
Nunez OF, Lopez, Rymer JA, , Tamama K., Case of sudden acute coma followed by spontaneous recovery. J Appl Lab Med 2018;3(3):507510.Google Scholar
Reeves, J, Duda, R. GHB/GBL intoxication and withdrawal: a review and case presentation. Addict Disord Treatment 2003;2:2528.Google Scholar
van Noordena MS, , Mol T, , Wisselink J, , Kuijpers W, , Boukje, AG. Dijkstra Treatment consumption and treatment re-enrollment in GHB-dependent patients in the Netherlands. Drug Alcohol Depend 2017;176:96101.Google Scholar
Dyer, JE, Roth, B, Hyma, BA. Gamma-hydroxybutyrate withdrawal syndrome. Ann Emerg Med 2001;37:147153.Google Scholar
Galloway, GP, Frederick, SL, Staggers, F. Physical dependence on sodium oxybate. Lancet 1994;343:57.Google Scholar
Wojtowicz, JM, Yarema, MC, Wax, PM. Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review. CJEM 2008;10(1):6974.Google Scholar
Kamal RM, , van Noorden MS, , Wannet W, , Beurmanjer H, , Dijkstra BAG, , Schellekens A. Pharmacological treatment in c-hydroxybutyrate (GHB) and c-butyrolactone (GBL) dependence: detoxification and relapse prevention. CNS Drugs 2017;31:5164. https://doi.org/10.1007/s40263-016-0402-zGoogle Scholar
Kamal RM, , van Noorden MS, , Wannet W, , Beurmanjer H, , Dijkstra BAG, , Schellekens A. Pharmacological treatment in c-hydroxybutyrate (GHB) and c-butyrolactone (GBL) dependence: detoxification and relapse prevention. CNS Drugs 2017;31:5164. https://doi.org/10.1007/s40263-016-0402-zGoogle Scholar
Wojtowicz, J. Withdrawal from gamma-hydroxybutyrate,1,4- butanediol and gamma-butyrolactone: a case report and systematic review. CJEM 2008;10(1):6974.Google Scholar
Mahr, G, Bishop, CL, Orringer, DJ. Prolonged withdrawal from extreme gamma-hydroxybutyrate (GHB) abuse. Psychosomatics 2001;42(5):439440.Google Scholar
Kamal RM, , van Noorden MS, , Wannet W, , et al. Pharmacological treatment in c-hydroxybutyrate (GHB) and c-butyrolactone (GBL) dependence: detoxification and relapse prevention. CNS Drugs 2017;31:5164. https://doi.org/10.1007/s40263-016-0402-zGoogle Scholar
Wood, DM, Dargan, PI. Development of a protocol for the management of acute gamma-hydroxy- butyrate (GHB) and gamma-butyrolactone (GBL) withdrawal. Clin Toxicol 2010;48:306.Google Scholar
Glasper, A, McDonough, M, Bearn, J. Within-patient variability in clinical presentation of gamma- hydroxybutyrate withdrawal: a case report. Eur Addict Res 2005;11(3):152154.Google Scholar
Kamal RM, , van Noorden MS, , Wannet W, , Beurmanjer H, , Dijkstra BAG, , Schellekens A. Pharmacological treatment in c-hydroxybutyrate (GHB) and c-butyrolactone (GBL) dependence: detoxification and relapse prevention. CNS Drugs 2017;31:5164. https://doi.org/10.1007/s40263-016-0402-zGoogle Scholar
Snead, OC. Gamma-hydroxybutyrate. Life Sci 1977;20:19351944.Google Scholar
van Noorden, MS, van Dongen, L, Zitman, FG, Vergouwen, T. Gamma-hydroxybutyrate withdrawal syndrome: dangerous but not well-known. Gen Hosp Psychiatry 2009;31:394396.Google Scholar
Miglani, JS, Kim, KY, Chahil, R. Gamma-hydroxy butyrate withdrawal delirium: a case report. Gen Hosp Psychiatry 2000;22:213215.Google Scholar
Hutto, B, Fairchild, A, Bright, R. Gamma-hydroxybutyrate withdrawal and chloral hydrate. Am J Psychiatry 2000;157:1706.Google Scholar
Hernandez, M, McDaniel, CH, Costanza, CD, Hernandez, OJ. GHB-induced delirium: a case report and review of the literature of gamma hydroxybutyric acid. Am J Drug Alcohol Abuse 1998;24:179183.Google Scholar
Catalano, MC, Glass, JM, Catalano, G, Burrows, S, Lynn, W, Weitzner, BS. Gamma butyrolactone (GBL) withdrawal syndromes. Psychosomatics 2001;42:8388.Google Scholar
Bowles, TM, Sommi, RW, Amiri, M. Successful management of prolonged gamma-hydroxybutyrate and alcohol withdrawal. Pharmacotherapy 2001;21:254257.Google Scholar
Mahr, G, Bishop, CL, Orringer, DJ. Prolonged withdrawal from extreme gamma-hydroxybutyrate (GHB) abuse. Psychosomatics 2001;42:439440.Google Scholar
McDaniel, CH, Miotto, KA. Gamma hydroxybutyrate (GHB) and gamma butyrolactone (GBL) withdrawal: five case studies. J Psychoactive Drugs 2001;33:143149.Google Scholar
Schneir, AB, Ly, HT, Clark, RF. A case of withdrawal from the GHB precursors gamma-butyrolactone and 1,4-butanediol. J Emerg Med 2001;21:3133.Google Scholar
Perez, E, Chu, J, Bania, T. Seven days of gamma-hydroxybutyrate (GHB) use produces severe withdrawal. Ann Emerg Med 2006;48:219220.Google Scholar
Zepf, FD, Holtmann, M, Duketis, E, et al. A 16-year-old boy with severe gamma-butyrolactone (GBL) withdrawal delirium. Pharmacopsychiatry 2009;42:202203.Google Scholar
Bennett, WRM, Wilson, LG, Roy-Byrne, PP. Gamma-hydroxybutyric acid (GHB) withdrawal: a case report. J Psychoactive Drugs 2007;39:293296.Google Scholar
Rosenberg, MH, Deerfield, LJ, Baruch, EM. Two cases of severe gamma-hydroxybutyrate withdrawal delirium on a psychiatric unit: recommendations for management. Am J Drug Alcohol Abuse 2003;29:487496.Google Scholar
Friedman, J, Westlake, R, Furman, M.Grievous bodily harm’: gamma hydroxybutyrate abuse leading to a Wernicke–Korsakoff syndrome. Neurology 1996;46:469471.Google Scholar
Addolorato, G, Caputo, F, Capristo, E, Bernardi, IM, Stefanini, GF, Gasbarrini, G. A case of gamma-hydroxybutyric acid withdrawal syndrome during alcohol addiction treatment: utility of diazepam administration. Clin Neuropharmacol 1999;22:6062.Google Scholar
Mycyk, MB, Wilemon, C, Aks, SE. Two cases of withdrawal from 1,4-butanediol use. Ann Emerg Med 2001;38:345346.Google Scholar
Price, G. In-patient detoxification after GHB dependence. Br J Psychiatry 2000;177:181.Google Scholar
Mullins, ME, Fitzmaurice, SC. Lack of efficacy of benzodiazepines in treating gamma-hydroxybutyrate withdrawal. J Emerg Med 2001;20:418420.Google Scholar
Constantinides, P, Vincent, P. Chronic gamma-hydroxybutyric acid use followed by gamma-hydroxybutyric acid withdrawal mimic schizophrenia: a case report. Cases J 2009;2:7520. https://doi.org/10.4076/1757-1626-2-7520Google Scholar
Claussen, M, Hassanpour, K, Jenewein, J, Boettger, S. Catatonic stupor secondary to gamma-hydroxy-butyric acid (GHB)-dependence and -withdrawal syndrome. Psychiatria Danubina 2014;26(4):358359.Google Scholar
Chien, J, Ostermann, G, Turkel, SB. Sodium oxybate-induced psychosis and suicide attempt in an 18-year-old girl. J Child Adolesc Psychopharmacol 2013;23(4):300301.Google Scholar
Kamal, RM, Dijkstra, BAG, de Weert-van Oene, GH, van Duren, JAM, De Jong, CAJ. Psychiatric comorbidity, psychological distress and quality of life in gamma-hydroxybutyrate (GHB) dependent patients. J Addict Dis 2016 (online). https://doi.org/10.1080/10550887.2016.1214000Google Scholar
Kamal RM, , van Noorden MS, , Wannet W, , Beurmanjer H, , Dijkstra BAG, , Schellekens A. Pharmacological treatment in c-hydroxybutyrate (GHB) and c-butyrolactone (GBL) dependence: detoxification and relapse prevention. CNS Drugs 2017;31:5164. https://doi.org/10.1007/s40263-016-0402-zGoogle Scholar
Kamal RM, , van Noorden MS, , Wannet W, , Beurmanjer H, , Dijkstra BAG, , Schellekens A. Pharmacological treatment in c-hydroxybutyrate (GHB) and c-butyrolactone (GBL) dependence: detoxification and relapse prevention. CNS Drugs 2017;31:5164. https://doi.org/10.1007/s40263-016-0402-zGoogle Scholar
Constantinides P, Vincent P. Chronic gamma-hydroxybutyric-acid use followed by gamma-hydroxybutyric-acid withdrawal mimic schizophrenia: a case report. Cases J 2009;2:7520.Google Scholar
Kuiper MA, Peikert N, Boerma EC. Gamma-hydroxybutyrate withdrawal syndrome: a case report. Cases J 2009;2:6530. https://doi.org/10.1186/1757-1626-2-6530Google Scholar
Snead, O, Gibson, KM. g-hydroxybutyric acid. N Engl J Med 2005;352(26):27212732.Google Scholar
Freese, TE, Miotto, K, Reback, CJ. The effects and consequences of selected club drugs. J Subst Abuse Treat 2002;23(2):151156.Google Scholar
Domınguez, Bruguera, I Balcells-Olivero´, P Batalla A., M Depression following c-hydroxybutyrate withdrawal: a case report. J Clin Psychopharmacol 2015;35(5):618619.Google Scholar
Miotto, K, Darakjian, J, Basch, J, Murray, S, Zogg, J, Rawson, R. Gamma-hydroxybutyric acid: patterns of use, effects and withdrawal. Am J Addict 2001;10(3):232241.Google Scholar
Heiligenberg, M, Wermeling, PR, van Rooijen, MS, et al . Recreational drug use during sex and sexually transmitted infections among clients of a city sexually transmitted infections clinic in Amsterdam, the Netherlands. Sex Transm Dis 2012;39(7):518527. https://doi.org/10.1097/OLQ.0b013e3182515601Google Scholar
Carey, JW, Mejia, R, Bingham, T, et al. Drug use, high-risk sex behaviors, and increased risk for recent HIV infection among men who have sex with men in Chicago and Los Angeles. AIDS Behav 2009;13(6):10841096. https://doi.org/10.1007/s10461-008-9403-3Google Scholar
Grov, C, Parsons, JT, Bimbi, DS, Sex and Love v3.0 Research Team. In the shadows of a prevention campaign: sexual risk behavior in the absence of crystal methamphetamine. AIDS Educ Prev 2008;20(1):4255. https://doi.org/10.1521/aeap.2008.20.1.42Google Scholar
Liao P-C, , Chang H-M, , Chen Y-L., Clinical management of gamma-hydroxybutyrate (GHB) withdrawal delirium with CIWA-Ar protocol. J Formos Med Assoc 2018;117(12):11241127.Google Scholar
Handelsman, L, Cochrane, KJ, Aronson, MJ, Ness, R, Rubinstein, KJ, Kanof, PD. Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse 1987;13:293308.Google Scholar
Winstock, AR, Mitcheson, L. New recreational drugs and the primary care approach to patients who use them. Br Med J 2012;344:e288. https://doi.org/10.1136/bmj.e288Google Scholar
Kamal RM, , van Noorden MS, , Wannet W, , Beurmanjer H, , Dijkstra BAG, , Schellekens A. Pharmacological treatment in c-hydroxybutyrate (GHB) and c-butyrolactone (GBL) dependence: detoxification and relapse prevention. CNS Drugs 2017;31:5164. https://doi.org/10.1007/s40263-016-0402-zGoogle Scholar
van Mechelen, JC, Dijkstra, BAG, Vergouwen, ACM. Severe illicit gamma-hydroxybutyric acid withdrawal in a pregnant woman: what to do? BMJ Case Rep 2019;12:e230997. https://doi.org/10.1136/bcr-2019-230997Google Scholar
Craig, K, Gomez, HF, McManus, JL, Bania, T. Sever gamma-hydroxybutyrate witdrawal: a case report and literature review. J Emerg Med 2000;18(1):6570.Google Scholar
McDonough, M, Kennedy, N, Glasper, A, Bearn, J. Clinical features and management of gamma-hydroxybutyrate (GHB) withdrawal: a review. Drug Alcohol Depend 2004;75(1):39.Google Scholar
McDaniel, C, Miotto, KA. Gamma hydroxybutyrate (GHB) and gamma butyrolactone (GBL) withdrawal: five case studies. J Psychoactive Drugs 2001;33:143149.Google Scholar
de Jong, C, Kamal, R, Dijkstra, BA, de Haan, HA. Gamma-hydroxybutyrate detoxification by titration and tapering. Eur Addict Res 2012;18(1):4045.Google Scholar
Chin, R. A case of severe withdrawal from gamma-hydroxybutyrate. Ann Emerg Med 2001;37(5):551552.Google Scholar
van Mechelen JC, Dijkstra BAG, Vergouwen ACM. Severe illicit gamma-hydroxybutyric acid withdrawal in a pregnant woman: what to do? BMJ Case Rep 2019;12:e230997. https://doi.org/10.1136/bcr-2019-230997Google Scholar
Floyd CN, , Wood DM, , Darganm PI. Baclofen in gamma-hydroxybutyrate withdrawal: patterns of use and online availability. Eur J Clin Pharmacol 2018;74:349356. https://doi.org/10.1007/s00228-017-2387-zGoogle Scholar
Beurmanjer H, , Kamal RM, , de Jong CAJ, , Dijkstra BAG, , Schellekens AFA. Baclofen to prevent relapse in gamma-hydroxybutyrate (GHB)-dependent patients: a multicentre, open-label, non-randomized, controlled trial. CNS Drugs 2018;32:437442. https://doi.org/10.1007/s40263-018-0516-6Google Scholar
Lingford-Hughes, A, Patel, Y, Bowden-Jones, O, et al. Improving GHB withdrawal with baclofen: study protocol for a feasibility study for a randomised controlled trial. Trials 2016;17:472. https://doi.org/10.1186/s13063-016-1593-9Google Scholar
Beurmanjer H, , Kamal RM, , de Jong CAJ, , Dijkstra BAG, , Schellekens AFA. Baclofen to prevent relapse in gamma-hydroxybutyrate (GHB)-dependent patients: a multicentre, open-label, non-randomized, controlled trial. CNS Drugs 2018;32:437442. https://doi.org/10.1007/s40263-018-0516-6Google Scholar
Habibian S, , Ahamad K, , McLean M, , Socias M., Successful management of gamma-hydroxybutyrate (GHB) withdrawal using baclofen as a standalone therapy: a case report. J Addiction Med 2019;13(5):415417. https://doi.org/10.1097/ADM.0000000000000514Google Scholar
Beurmanjer H, , Kamal RM, , de Jong CAJ, , Dijkstra BAG, , Schellekens AFA. Baclofen to prevent relapse in gamma-hydroxybutyrate (GHB)-dependent patients: a multicentre, open-label, non-randomized, controlled trial. CNS Drugs 2018;32:437442. https://doi.org/10.1007/s40263-018-0516-6Google Scholar
Dijkstra BAG, Kamal R, van Noorden MS, , de Haan H, , Loonen AJM, , De Jong CAJ. Detoxification with titration and tapering in gamma-hydroxybutyrate (GHB) dependent patients: the Dutch GHB monitor project. Drug Alcohol Depend 2017;170164170173. https://doi.org/10.1016/j.drugalcdep.2016.11.014Google Scholar
Kamal, RM, van Noorden, MS, Wannet, W, et al. Pharmacological treatment in c-hydroxybutyrate (GHB) and c-butyrolactone (GBL) dependence: detoxification and relapse prevention. CNS Drugs 2017;31:5164. https://doi.org/10.1007/s40263-016-0402-zGoogle Scholar
Beurmanjer H, , Kamal RM, , de Jong CAJ, , Dijkstra BAG, , Schellekens AFA. Baclofen to prevent relapse in gamma-hydroxybutyrate (GHB)-dependent patients: a multicentre, open-label, non-randomized, controlled trial. CNS Drugs 2018;32:437442. https://doi.org/10.1007/s40263-018-0516-6Google Scholar
Lingford-Hughes, A, Patel, Y, Bowden-Jones, O, et al. Improving GHB withdrawal with baclofen: study protocol for a feasibility study for a randomised controlled trial. Trials 2016;17:472. https://doi.org/10.1186/s13063-016-1593-9Google Scholar
Beurmanjer H, , Kamal RM, , de Jong CAJ, , Dijkstra BAG, , Schellekens AFA. Baclofen to prevent relapse in gamma-hydroxybutyrate (GHB)-dependent patients: a multicentre, open-label, non-randomized, controlled trial. CNS Drugs 2018;32:437442. https://doi.org/10.1007/s40263-018-0516-6Google Scholar
Beurmanjer H, , Kamal RM, , de Jong CAJ, , Dijkstra BAG, , Schellekens AFA. Baclofen to prevent relapse in gamma-hydroxybutyrate (GHB)-dependent patients: a multicentre, open-label, non-randomized, controlled trial. CNS Drugs 2018;32:437442. https://doi.org/10.1007/s40263-018-0516-6Google Scholar
Beurmanjer H, , Kamal RM, , de Jong CAJ, , Dijkstra BAG, , Schellekens AFA. Baclofen to prevent relapse in gamma-hydroxybutyrate (GHB)-dependent patients: a multicentre, open-label, non-randomized, controlled trial. CNS Drugs 2018;32:437442. https://doi.org/10.1007/s40263-018-0516-6Google Scholar
Habibian S, , Ahamad K, , McLean M, , Socias, M. Successful management of gamma-hydroxybutyrate (GHB) withdrawal using baclofen as a standalone therapy: a case report. J Addict Med 2019;13(5):415417.Google Scholar
Beurmanjer H, , Kamal RM, , de Jong CAJ, , Dijkstra BAG, , Schellekens AFA. Baclofen to prevent relapse in gamma-hydroxybutyrate (GHB)-dependent patients: a multicentre, open-label, non-randomized, controlled trial. CNS Drugs 2018;32:437442. https://doi.org/10.1007/s40263-018-0516-6Google Scholar
Addolorato, G, Caputo, F, Capristo, E, et al. Diazepam in the treatment of GHB dependence. Br J Psychiatry 2001;178:183 (letter).Google Scholar
Dyer, JE, Andrews, KM. Gamma hydroxybutyrate withdrawal. J Toxicol Clin Toxicol 1997;35:553554.Google Scholar
Eiden, C, Capdevielle, D, Deddouche, C, Boulenger, JP, Blayac, JP, Peyrière, H. Neuroleptic malignant syndrome-like reaction precipitated by antipsychotics in a patient with gamma-butyrolactone withdrawal. J Addict Med 2011;5(4):302303. https://doi.org/10.1097/ADM.0b013e3182236730Google Scholar
Veerman Selene ATE, , Veerman RT. Current developments regarding GHB and GBL incidents, treatment and detection: a qualitative review. World J Pharm Res 2019;8(7):1126.Google Scholar
Floyd CN, , Wood DM, , Dargan PI. Baclofen in gamma-hydroxybutyrate withdrawal: patterns of use and online availability. Eur J Clin Pharmacol 2018;74:349356. https://doi.org/10.1007/s00228-017-2387-zGoogle Scholar
Kamal, RM, Qurishi, R, De Jong, CA. Baclofen and γ-hydroxybutyrate (GHB), a dangerous combination. J Addict Med 2015;9(1):7577. https://doi.org/10.1097/ADM.0000000000000084Google Scholar
de Jong, C, Kamal, R, Dijkstra, BA, de Haan, HA. Gamma-hydroxybutyrate detoxification by titration and tapering. Eur Addict Res 2012;18(1):4045.Google Scholar
van Raay, MEJ. GHB-onttrekkingsverschijnselen behandeled met diazepam, baclofen en propranolol. Psyfar 2012;2:2225.Google Scholar
Bell, J, Gamma-butyrolactone, Collins R. (GBL) dependence and withdrawal. Addiction 2011;106(2):442447.Google Scholar
de Weert-van Oene, GH, Schellekens, AF, Dijkstra, BA, Kamal, R, de Jong, CA. Detoxification of patients with GHB dependence. Tijdschr Psychiatr Dutch 2013;55(11):885890.Google Scholar
Stalcup, J, Wylie, B, Stalcup, SA. Outpatient treatment for GHB dependence. In: T Porrata, , ed. G’d Up” 24/7: The GHB Addiction Guide. Sam Clemente, CA: LawTech Publishing, 2007.Google Scholar
Kamal, RM, van Noorden, MS, Wannet, W, Beurmanjer, H, Dijkstra, BA, Schellekens, A. Pharmacological treatment in γ-hydroxybutyrate (GHB) and γ-butyrolactone (GBL) dependence: detoxification and relapse prevention. CNS Drugs 2017;31(1):5164.Google Scholar
Kamal, RM, van Noorden, MS, Wannet, W, Beurmanjer, H, Dijkstra, BA, Schellekens, A. Pharmacological treatment in γ-hydroxybutyrate (GHB) and γ-butyrolactone (GBL) dependence: detoxification and relapse prevention. CNS Drugs 2017;31(1):5164.Google Scholar
McDonough, M, Kennedy, N, Glasper, A, Bearn, J. Clinical features and management of gamma-hydroxybutyrate (GHB) withdrawal: a review. Drug Alcohol Depend 2004;75(1):39.Google Scholar
Kamal, RM, van Iwaarden, S, Dijkstra, BA, de Jong, CA. Decision rules for GHB (c-hydroxybutyric acid) detoxification: a vignette study. Drug Alcohol Depend 2014;135:146151.Google Scholar
Kamal, R, De Jong, CAJ. Practice-Based Recommendations for the Detoxification of Patients with GHB Abuse Disorders in an Outpatient Setting. Nijmegen, Nijmegen Institute for Scientist Practitioners in Addiction (NISPA), 2013.Google Scholar
McDonough, M, Kennedy, N, Glasper, A, Bearn, J. Clinical features and management of gamma-hydroxybutyrate (GHB) withdrawal: a review. Drug Alcohol Depend 2004;75(1):39.Google Scholar
McDonough, M, Kennedy, N, Glasper, A, Bearn, J. Clinical features and management of gamma-hydroxybutyrate (GHB) withdrawal: a review. Drug Alcohol Depend 2004;75(1):39.Google Scholar
Bell, J, Gamma-butyrolactone, Collins R. (GBL) dependence and withdrawal. Addiction 2011;106(2):442447.Google Scholar
McDonough, M, Kennedy, N, Glasper, A, Bearn, J. Clinical features and management of gamma-hydroxybutyrate (GHB) withdrawal: a review. Drug Alcohol Depend 2004;75(1):39.Google Scholar
Ghio, L, Cervetti, A, Respino, M, Belvederi Murri, M, Amore, M. Management and treatment of gamma butyrolactone withdrawal syndrome: a case report and review. J Psychiatr Pract 2014;20(4):294300.Google Scholar
Project GHB. 2002.Google Scholar
Zepf, FD, Holtmann, M, Duketis, E, et al. Withdrawal syndrome after abuse of GHB (gamma-hydroxybutyrate) and its physiological precursors – its relevance for child and adolescent psychiatrists. Z Kinder Jugendpsychiatr Psychother 2009;37(5):413420. https://doi.org/10.1024/1422-4917.37.5.413Google Scholar
Kamal, RM, Iwaarden, S Jong, CAJ. Decision rules for GHB (gamma-hydroxybutyric acid) detoxification: a vignette study.Google ScholarGoogle Scholar
Dijkstra, B, De Weert-van Oene, GH, Verbrugge, CAG, De Jong, C. End report GHB detoxification with pharmaceutical GHB DeTiTap monitor, in the Netherlands addiction care. Nijmegen, Nijmegen Institute for Scientist-Practitioners in Addiction, 2013.Google Scholar
Cappetta, M, Murnion, BP. In-patient management of gamma-hydroxybutyrate withdrawal. Australas Psychiatry 2019;27(3):284287. https://doi.org/10.1177/1039856218822748Google Scholar
van Noordena MS, , Mol T, , Wisselink J, , Kuijpers W, , Dijkstra BAG. Treatment consumption and treatment re-enrollment in GHB-dependent patients in the Netherlands. Drug Alcohol Depend 2017;176:96101.Google Scholar
Dijkstra, BAG, DeWeert-Van Oene, GH, Verbrugge, CAG, De Jong, CAJ. GHB-Detoxification Using Pharmaceutical GHB; Report from DeTiTap®-Monitoring in Dutch Addiction Care. NISPA, Nijmegen, The Netherlands, 2013.Google Scholar
Beurmanjer, H, Verbrugge, CAG, Schrijen, S, Schellekens, AFA, De Jong, CAJ, Dijkstra, BAG. Treatment of GHB-Dependence after Detoxification; Report NISPA GHB Monitor 2.0. NISPA, Nijmegen, The Netherlands.Google Scholar
Beurmanjer, H, Asperslag, EM, Verbrugge, CAG, et al. GHB-Dependence: Disease Perceptions and Need for Treatment. NISPA, Nijmegen, The Netherlands.Google Scholar
van Noordena MS, , Mol T, , Wisselink J, , Kuijpers W, , Dijkstra BAG. Treatment consumption and treatment re-enrollment in GHB-dependent patients in the Netherlands. Drug Alcohol Depend 2017;176:96101.Google Scholar
Busardò, FP, Varì MR, , Di Trana A, , Malaca S, , Carlier J, , Di Luca NM., Drug-facilitated sexual assaults (DFSA): a serious underestimated issue. Eur Rev Med Pharmacol Sci 2019;23:1057710587.Google Scholar
Németh, Z, Kun, B, Demetrovics, Z. The involvement of gamma-hydroxybutyrate in reported sexual assaults: a systematic review. J Psychopharmacol 2010;24(9):12811287.Google Scholar
Veerman ATE, , Veerman SRT. Current developments regarding GHB and GBL incidents, treatment and detection: a qualitative review. World J Pharm Res (online) 2019;8(7). www.researchgate.net/profile/Selene-Veerman/publication/333565737Google Scholar
Pettigrew, M. Somnophilia and sexual abuse through the administration of GHB and GBL. J Forensic Sci 2019;64(1). https://doi.org/10.1111/1556-4029.13812Google Scholar
Bracchi, M, Stuart, D, Castles, R, Khoo, S, Back, D, Boffito, M. Increasing use of ‘party drugs’ in people living with HIV on antiretrovirals: a concern for patient safety. Aids 2015;29(13):15851592.Google Scholar
Jones, AW, Holmgren, A, Kugelberg, FC. Driving under the influence of gamma-hydroxybutyrate (GHB). Forensic Sci Med Pathol 2008;4(4):205211. https://doi.org/10.1007/s12024-008-9040-1Google Scholar

References

Votaw, VR, Geyer, R, Rieselbach, MM, McHugh, RK. The epidemiology of benzodiazepine misuse: a systematic review. Drug Alcohol Depend 2019;200:95114. https://doi.org/10.1016/j.drugalcdep.2019.02.033Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). The misuse of benzodiazepines among high-risk opioid users in Europe. Perspectives on Drugs (PODs). EMCDDA, Lisbon, 2018. Available at: www.emcdda.europa.eu/system/files/publications/2733/Misuse%20of%20benzos_POD2015.pdfGoogle Scholar
European Monitoring Centre for Drugs and Drug Addiction and Europol. EU Drug Markets Report 2019. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction and Europol. EU Drug Markets Report 2019. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
Advisory Council on the Misuse of Drugs. Novel Benzodiazepines. A Review of the Evidence of Use and Harms of Novel Benzodiazepines. Published April 2020.Google Scholar
Busardò, FP, Trana, A, Montanari, E, Mauloni, S, Tagliabracci, A, Giorgetti, R. Is etizolam a safe medication? Effects on psychomotor performance at therapeutic dosages of a newly abused psychoactive substance. Forensic Sci Int 2019;301:137141.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). The misuse of benzodiazepines among high-risk opioid users in Europe. Perspectives on Drugs (PODs). EMCDDA, Lisbon, 2018. Available at: www.emcdda.europa.eu/system/files/publications/2733/Misuse%20of%20benzos_POD2015.pdfGoogle Scholar
Jann, M, Kennedy, WK, Lopez, G. Benzodiazepines: a major component in unintentional prescription drug overdoses with opioid analgesics. J Pharm Prac 2014;27(1):516.Google Scholar
Advisory Council on the Misuse of Drugs. Novel Benzodiazepines. A Review of the Evidence of Use and Harms of Novel Benzodiazepines. Published April 2020.Google Scholar
Zawilska, JB, Wojcieszak J. An expanding world of new psychoactive substances: designer benzodiazepines. Neuro Toxicology 2019;73:816.Google Scholar
United Nations Office on Drugs and Crime (UNODC). World Drug Report 2018. Executive Summary Conclusions and Policy Implications. Available at: www.unodc.org/wdr2018/prelaunch/WDR18_Booklet_1_EXSUM.pdf [last accessed 24 February 2022].Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Advice on U-47,700, etizolam and other designer benzodiazepines. Home Office, London, 2016.Google Scholar
Zawilska, JB, Wojcieszak, J. An expanding world of new psychoactive substances: designer benzodiazepines. NeuroToxicology 2019;73:816.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. Fentanils and synthetic cannabinoids: driving greater complexity into the drug situation. An update from the EU Early Warning System (June 2018). Publications Office of the European Union, Luxembourg, 2018.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2019: Trends and Developments. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
Manchester, KR, Lomas, EC, Waters, L, Dempsey, FC, Maskell, PD. The emergence of new psychoactive substance (NPS) benzodiazepines: a review. Drug Test Anal 2017;10(1):3753.Google Scholar
Zawilska, JB, Wojcieszak, J. An expanding world of new psychoactive substances: designer benzodiazepines. NeuroToxicology 2019;73:816.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction and Europol. EU Drug Markets Report 2019. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
Manchester, KR, Lomas, EC, Waters, L, Dempsey, FC, Maskell, PD. The emergence of new psychoactive substance (NPS) benzodiazepines: a review. Drug Test Anal 2017;10(1):3753. https://doi.org/10.1002/dta.2211Google Scholar
Ameline, A, Richeval, C, Gaulier, J-M, Raul, J-S, Kintz, P. Detection of the designer benzodiazepine flunitrazolam in urine and preliminary data on its metabolism. Drug Test Anal 2019;11(2):223229.Google Scholar
Mortelé, O, Vervliet, P, Gys, C, et al. In vitro Phase I and Phase II metabolism of the new designer benzodiazepine cloniprazepam using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. J Pharm Biomed Anal 2018;153:158167. https://doi.org/10.1016/j.jpba.2018.02.032Google Scholar
Pettersson Bergstrand, M, Richter, LHJ, Maurer, HH, Wagmann, L, Meyer, MR. In vitro glucuronidation of designer benzodiazepines by human UDP‐glucuronyltransferases. Drug Test Anal 2019;11:4550.Google Scholar
Orsolini, L, Corkery, JM, Chiappini, S, et al. ‘New/Designer Benzodiazepines’: an analysis of the literature and psychonauts’ trip reports. Curr Neuropharmacol 2020 (online). https://doi.org/10.2174/1570159x18666200110121333Google Scholar
Abouchedid, R, Gilks, T, Dargan, PI, Archer, JRH, Wood, DM. Assessment of the availability, cost, and motivations for use over time of the new psychoactive substances benzodiazepines diclazepam, flubromazepam, and pyrazolam in the UK. J Med Toxicol 2018;14:134143. https://doi.org/10.1007/s13181-018-0659-3Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Designer Benzodiazepines. A Review of the Evidence of Use and Harms 2016.Google Scholar
Abouchedid, R, Gilks, T, Dargan, PI, Archer, JRH, Wood, DM. Assessment of the availability, cost, and motivations for use over time of the new psychoactive substances – benzodiazepines diclazepam, flubromazepam, and pyrazolam – in the UK. J Med Toxicol 2018;14:134143. https://doi.org/10.1007/s13181-018-0659-3Google Scholar
Murphy, L, Melamed, J, Gerona, R, Hendrickson, RG. Clonazolam: a novel liquid benzodiazepine. Toxicol Commun 2019;3(1):7578https://doi.org/10.1080/24734306.2019.1661568Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2019: Trends and Developments. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
United Nations Office on Drugs and Crime (UNODC). World Drug Report 2018. Executive Summary Conclusions and Policy Implications. Available at: www.unodc.org/wdr2018/prelaunch/WDR18_Booklet_1_EXSUM.pdf [last accessed 24 February 2022].Google Scholar
World Drug Report 2019 (United Nations publication, Sales No. E.19.XI.8).Google Scholar
United Nations Office on Drugs and Crime (UNODC). World Drug Report 2018. Executive Summary Conclusions and Policy Implications. Available at: www.unodc.org/wdr2018/prelaunch/WDR18_Booklet_1_EXSUM.pdf [last accessed 24 February 2022].Google Scholar
Votaw, VR, Geyer, R, Rieselbach, MM, McHugh, RK. The epidemiology of benzodiazepine misuse: a systematic review. Drug Alcohol Depend 2019;200:95114.Google Scholar
Office of National Statistics. Drug misuse in England and Wales: year ending March 2020. An overview of the extent and trends of illicit drug use for the year ending March 2020. Data are from the Crime Survey for England and Wales.Google Scholar
El Balkhi, S, Monchaud, C, Herault, F, Geniaux, H, Saint-Marcoux, F. Designer benzodiazepines’ pharmacological effects and potencies: how to find the information. J Psychopharmacol 2020;1:2. https://doi.org/10.1177/0269881119901096Google Scholar
Advisory Council on the Misuse of Drugs. Advice on U-47,700, etizolam and other designer benzodiazepines. London, Home Office, 2016.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction and Europol. EU Drug Markets Report 2019. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
Abouchedid, R, Gilks, T, Dargan, PI, Archer, JRH, Wood, DM. Assessment of the availability, cost, and motivations for use over time of the new psychoactive substances benzodiazepines diclazepam, flubromazepam, and pyrazolam in the UK. J Med Toxicol 2018;14:134143. https://doi.org/10.1007/s13181-018-0659-3Google Scholar
Advisory Council on the Misuse of Drugs. Novel Benzodiazepines. A Review of the Evidence of Use and Harms of Novel Benzodiazepines. April 2020Google Scholar
Luethi D, Liechti ME. Designer drugs: mechanism of action and adverse effects. Arch Toxicol (online). https://doi.org/10.1007/s00204-020-02693-7Google Scholar
Schepis, TS, Teter, CJ, Simoni-Wastila, L, McCabe, S. Esteban prescription tranquilizer/sedative misuse prevalence and correlates across age cohorts in the US. Addict Behav 2018;87:2432.Google Scholar
Kurtz, SP, Surratt, HL, Levi-Minzi, MA, Mooss, A. Benzodiazepine dependence among multidrug users in the club scene. Drug Alcohol Depend 2011;119(1–2):99105.Google Scholar
Kecojevic, A, Corliss, HL, Lankenau, SE. Motivations for prescription drug misuse among young men who have sex with men (YMSM) in Philadelphia. Int J Drug Policy 2015;26(8):764771. https://doi.org/10.1016/j.drugpo.2015.03.010Google Scholar
Kurtz, SP, Surratt, HL, Levi-Minzi, MA, Mooss, A. Benzodiazepine dependence among multidrug users in the club scene. Drug Alcohol Depend 2011;119(1–2):99105.Google Scholar
Inciardi, JA, Surratt, HL, Kurtz, SP, Cicero, TJ. Mechanisms of prescription drug diversion among drug-involved club- and street-based populations. Pain Med 2007; 8(2):171183.Google Scholar
Vogel, M, Knopfli, B, Schmid, O, et al.Treatment or ‘high’: benzodiazepine use in patients on injectable heroin or oral opioids. Addict Behav 2013;38:24772484.Google Scholar
Advisory Council on the Misuse of Drugs. Novel Benzodiazepines. A Review of the Evidence of Use and Harms of Novel Benzodiazepines. April 2020.Google Scholar
Wines, JD, Saitz, R, Horton, NJ, Lloyd-Travaglini, C, Samet, JH. Suicidal behaviour, drug use and depressive symptoms after detoxification: a 2-year prospective study. Drug Alcohol Depend 2004;76:S2129.Google Scholar
Backmund, M, Meyer, K, Schütz, C, Reimer, J. Factors associated with suicide attempts among injection drug users. Subst Use Misuse 2011;46:15531559.Google Scholar
Sun, E, Dixit, A, Humphreys, K, Darnall, B, Baker, L, Mackey, S. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. Br Med J 2017;356:j760.Google Scholar
Chen, K, Berger, C, Forde, D, D’Adamo, C, Weintraub, E, Gandhi, D. Benzodiazepine use and misuse among patients in a methadone program. BMC Psychiatry 2011;11(1):90.Google Scholar
Sun, E, Dixit, A, Humphreys, K, Darnall, B, Baker, L, Mackey, S. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. Br Med J 2017;356:j760.Google Scholar
Deacon, RM, Nielsen, S, Leung, S, et al. Alprazolam use and related harm among opioid substitution treatment clients – 12 months follow up after regulatory rescheduling. Int J Drug Policy 2016;36:104111.Google Scholar
Kay, C, Fergestrom, N, Spanbauer, C, Jackson, J. Opioid dose and benzodiazepine use among commercially insured individuals on chronic opioid therapy. Pain Med 2019;21(6):17.Google Scholar
Kamal, F, Flavin, S, Campbell, F, et al. Factors affecting the outcome of methadone maintenance treatment in opiate dependence. Irish Med J. 2007;100(3):393397.Google Scholar
Meiler, A, Mino, A, Chatton, A, Broers, B. Benzodiazepine use in a methadone maintenance programme: patient characteristics and the physician’s dilemma. Schweiz Arch Neurol Psychiatr 2005;156:310317.Google Scholar
Peles, E, Schreiber, S, Adelsona, M. 15-Year survival and retention of patients in a general hospital-affiliated methadone maintenance treatment (MMT) center in Israel. Drug Alcohol Depend 2010; 107:141148.Google Scholar
Lavie, E, Fatséas, M, Denis, C, Auriacombe, M. Benzodiazepine use among opiate-dependent subjects in buprenorphine maintenance treatment: correlates of use, abuse and dependence. Drug Alcohol Depend 2009; 99:338344.Google Scholar
Darke, S, Hall, W, Ross, M, Wodak, A. Benzodiazepine use and HIV risk-taking behaviour among injecting drug users. Drug Alcohol Depend 1992;31(1):3136.Google Scholar
NICE hypnotics and anxiolytics. Available at: https://bnf.nice.org.uk/treatment-summary/hypnotics-and-anxiolytics.html [last accessed 24 February 2022].Google Scholar
NICE hypnotics. Available at: www.nice.org.uk/advice/KTT6/chapter/Evidence-context [last accessed 24 February 2022].Google Scholar
NICE benzodiazepine and z-drug withdrawal. Available at: https://cks.nice.org.uk/topics/benzodiazepine-z-drug-withdrawal/management/benzodiazepine-z-drug-withdrawal/ [last accessed 24 February 2022].Google Scholar
Baandrup L, EbdrupBH, Rasmussen JO, Lindschou J, Gluud C, Glenthøj BY. Pharmacological interventions for benzodiazepine discontinuation in chronic benzodiazepine users. Cochrane Systematic Review – Intervention Version published 15 March 2018. https://doi.org/10.1002/14651858.CD011481.pub2. Available at: www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011481.pub2/full [last accessed 24 February 2022].Google Scholar
Darker, CD, Sweeney, BP, Barry, JM, Farrell, MF, Donnelly‐Swift, E. Psychosocial interventions for benzodiazepine harmful use, abuse or dependence. Cochrane Systematic Review – Intervention Version published 11 May 2015. https://doi.org/10.1002/14651858.CD009652.pub2Google Scholar
Denis, C, Fatséas, M, Lavie, E, Auriacombe, M. Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings. Cochrane Database Syst Rev 2006;(3):CD005194.Google Scholar
Tiihonen, J, Mittendorfer-Rutz, E, Torniainen, M, Alexanderson, K, Tanskanen, A. Mortality and cumulative exposure to antipsychotics, antidepressants, and benzodiazepines in patients with schizophrenia: an observational follow-up study. Am J Psychiatry 2016;173:600606.Google Scholar
Kang, M, Ghassemzadeh, S. Benzodiazepine toxicity. [Updated 8 March 2019.] In Treasure Island. StatPearls Publishing, Florida, 2019.Google Scholar
TOXBASE www.toxbase.org [last accessed 27 February 2019].Google Scholar
TOXBASE www.toxbase.org [last accessed 27 February 2019].Google Scholar
Orsolini, L, Corkery, JM, Chiappini, S, et al. ‘New/Designer Benzodiazepines’: an analysis of the literature and psychonauts’ trip reports. Curr Neuropharmacol 2020 (online). https://doi.org/10.2174/1570159x18666200110121333Google Scholar
Luethi, D, Liechti, ME. Designer drugs: mechanism of action and adverse effects. Arch Toxicol 20200;94(4):10851133.Google Scholar
Zawilska, JB, Wojcieszak, J. An expanding world of new psychoactive substances: designer benzodiazepines. NeuroToxicology 2019;73:816. https://doi.org/10.1016/j.neuro.2019.02.015Google Scholar
Moosmann, B, King, LA, Auwarter, V. Designer benzodiazepines: a new challenge. Psychiatry 2015;14:2.Google Scholar
Bohnenberger, K, Liu, MT. Flubromazolam overdose: a review of a new designer benzodiazepine and the role of flumazenil. Mental Health Clinician 2019;9(3):133137https://doi.org/10.9740/mhc.2019.05.133Google Scholar
Ameline, A, Richeval, C, Gaulier, J-M, Raul, J-S, Kintz, P. Characterization of flunitrazolam, a new designer benzodiazepine, in oral fluid after a controlled single administration. J Anal Toxicol 2018;42:e58e60. https://doi.org/10.1093/jat/bky012Google Scholar
O’Brien, CP. Benzodiazepine use, abuse, and dependence. J Clin Psychiatry 2005;66:2833.Google Scholar
Moosmann, B, Huppertz, LM, Hutter, M, et al. Detection and identification of the designer benzodiazepine flubromazepam and preliminary data on its metabolism and pharmacokinetics. J Mass Spectrom 2013;48:11501159.Google Scholar
Moodmann, B, King, AL, Auwa¨rter, V. Designer benzodiazepines: a new challenge. World Psychiatry 2015;14:2.Google Scholar
Moosmann, B, Bisel, P, Auwa¨rter, V. Characterization of the designer benzodiazepine diclazepam and preliminary data on its metabolism and pharmacokinetics. Drug Test Anal 2014;6:757763.Google Scholar
Schifano, F, Orsolini, L, Papanti, GD, et al. Novel psychoactive substances of interest for psychiatry. World Psychiatry 2015;14:1526.Google Scholar
Nakamae, T, Shinozuka, T, Sasaki, C, et al. Case report: etizolam and its major metabolites in two unnatural death cases. Forensic Sci Int 2008;20:182.Google Scholar
WEDINOS. PHILTRE Annual Report 2020-2021. Available at: www.wedinos.org/resources/downloads/Annual-Report-20-21-English.pdf [last accessed 23 April 2022].Google Scholar
Public Health England. RIDR SUMMARY – MAY 2019. Report unexpected or severe adverse reactions to illicit drugs. Available at: www.gov.uk/government/publications/drug-health-harms-national-intelligence/national-intelligence-network-on-drug-health-harms-briefing-april-2019?msclkid=216cf526c26d11ec94c0857fb53f773f [last accessed 23 April 2022].Google Scholar
Runnstrom MC, Kalra SS, Lascano J, Patel DC. Designer Drug Diclazepam: A Journey from Death to Life. C42. Critical Care Case Reports: Toxicology and Poisonings.Google Scholar
Bäckberg, M, Pettersson Bergstrand, M, Beck, O, Helander, A. Occurrence and time course of NPS benzodiazepines in Sweden – results from intoxication cases in the STRIDA project. Clin Toxicol 2019;57(3):203212https://doi.org/10.1080/15563650.2018.1506130Google Scholar
National Records of Scotland (NRS). Drug-related deaths in Scotland in 2018. Edinburgh, National Records of Scotland, 2019.Google Scholar
Novak, SP, Håkansson, A, Martinez-Raga, J, Reimer, J, Krotki, K, Varughese, S. Nonmedical use of prescription drugs in the European Union. BMC Psychiatry 2016;16:274. https://doi.org/10.1186/s12888-016–0909–3Google Scholar
Bonar, EE, Cunningham, RM, Chermack, ST, et al. Prescription drug misuse and sexual risk behaviors among adolescents and emerging adults. J Stud Alcohol Drugs 2014;75(2):259268.Google Scholar
Benotsch, EG, Koester, S, Luckman, D, Martin, AM, Cejka, A. Non-medical use of prescription drugs and sexual risk behavior in young adults. Addict Behav 2011;36:152155.Google Scholar
Clayton, HB, Lowry, R, August, E, Everett Jones, S. Nonmedical use of prescription drugs and sexual risk behaviors. Pediatrics 2016;137(1).Google Scholar
Jones KA, Nielsen S, Bruno R, Frei M, Lubman DI. Benzodiazepines: their role in aggression and why GPs should prescribe with caution. Aust Fam Physician 2011;40(11):862–865.Google Scholar
Albrecht, B, Staiger, P, Hall, K, Miller, P, Best, D, Lubman, D. Benzodiazepine use and aggressive behaviour: a systematic review. Aust N Z J Psychiatry 2014;48(12):10961114.Google Scholar
Advisory Council on the Misuse of Drugs. Novel Benzodiazepines. A Review of the Evidence of Use and Harms of Novel Benzodiazepines. April 2020.Google Scholar
Advisory Council on the Misuse of Drugs. NPS Committee Meeting Paper: Benzodiazepines. Published 2015.Google Scholar
O’Connor, LC, Torrance, HJ, McKeown, DA. ELISA detection of phenazepam, etizolam, pyrazolam, flubromazepam, diclazepam and delorazepam in blood using Immunalysis® benzodiazepine kit. J Anal Toxicol 2016;40:159161. https://doi.org/10.1093/jat/bkv122Google Scholar
Penninga, EI, Graudal, N, Ladekarl, MB, Jurgens, G. Adverse events associated with flumazenil treatment for the management of suspected benzodiazepine intoxication – a systematic review with meta-analyses of randomised trials. Basic Clin Pharmacol Toxicol 2016;118:3744. https://doi.org/10.1111/bcpt.12434Google Scholar
Bäckberg, M, Pettersson Bergstrand, M, Beck, O, Helander, A. Occurrence and time course of NPS benzodiazepines in Sweden – results from intoxication cases in the STRIDA project, Clin Toxicol 2019;57(3):203212https://doi.org/10.1080/15563650.2018.1506130Google Scholar
Barker, MJ, Greenwood, KM, Jackson, M, Crowe, SF. Cognitive effects of long-term benzodiazepine use: a meta-analysis. CNS Drugs 2004;18:3748.Google Scholar
McAndrews, M, Weiss, RT, Sandor, P, Taylor, A, Carlen, PL, Shapiro, CM. Cognitive effects of long-term benzodiazepine use in older adults. Hum Psychopharmacol 2003;18:5157.Google Scholar
French, DD, Chirikos, TN, Spehar, A, Campbell, R, Means, H, Bulat, T. Effect of concomitant use of benzodiazepines and other drugs on the risk of injury in a veteran population. Drug Saf 2005;28:11411150.Google Scholar
Airagnes, G, Pelissolo, A, Lavallee, M, Flament, M, Limosin, F. Benzodiazepine misuse in the elderly: risk factors, consequences, and management. Curr Psychiatry Rep 2016;18:89.Google Scholar
Lader, MH. Limitations on the use of benzodiazepines in anxiety and insomnia: are they justified? Eur Neuropsychopharmacol 1999;9(Suppl. 6):S399S405.Google Scholar
Pariente, A, de Gage, SB, Moore N, Bégaud B. The benzodiazepine-dementia disorders link: current state of knowledge. CNS Drugs 2016;30:17.Google Scholar
Buffett-Jerrott, SE, Stewart, SH. Cognitive and sedative effects of benzodiazepine use. Curr Pharm Des 2002;8:4558.Google Scholar
Lader, M, Tylee, A, Donoghue, J. Withdrawing benzodiazepines in primary care. CNS Drugs 2009;23:1934.Google Scholar
Mura, T, Proust-Lima, C, Akbaraly, T, et al. Chronic use of benzodiazepines and latent cognitive decline in the elderly: results from the Three-City Study. Eur Neuropsychopharmacol 2013;23:212223.Google Scholar
Lader, M, Tylee, A, Donoghue, J. Withdrawing benzodiazepines in primary care. CNS Drugs 2009;23:1934.Google Scholar
Koyama, A, Steinman, M, Ensrud, K, Hillier, TA, Yaffe, K. Ten-year trajectory of potentially inappropriate medications in very old women: importance of cognitive status. J Am Geriatr Soc 2013;61:258263.Google Scholar
Pisani, MA, Murphy, TE, Araujo, KL, Slattum, P, Van Ness, PH, Inouye, SK. Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population. Crit Care Med 2009;37:177183.Google Scholar
de las Cuevas, C, Sanz, E, de la Fuente, J. Benzodiazepines: more ‘behavioural’ addiction than dependence. Psychopharmacology (Berl) 2003;167:297303.Google Scholar
Soyka, M. Treatment of benzodiazepine dependence. N Engl J Med 2017;376:11471157. https://doi.org/10.1056/NEJMra1611832Google Scholar
Zawilska, JB, Wojcieszak, J. An expanding world of new psychoactive substances: designer benzodiazepines. Neurotoxicology 2019;73:816. https://doi.org/10.1016/j.neuro.2019.02.015Google Scholar
Andersson, M, Kjellgren, A. The slippery slope of flubromazolam: experiences of a novel psychoactive benzodiazepine as discussed on a Swedish online forum. Nord Stud Alcohol Drugs 2017;34(3):217229. https://doi.org/10.1177/1455072517706304Google Scholar
Zawilska, JB, Wojcieszak, J. An expanding world of new psychoactive substances: designer benzodiazepines. Neurotoxicology 2019;73:816. https://doi.org/10.1016/j.neuro.2019.02.015Google Scholar
Parker, GB, Graham, RK. Clinical characteristics associated with treatment-resistant bipolar disorder. J Nerv Ment Dis 2017;205:188191.Google Scholar
Bjorklund, L, Horsdal, HT, Mors, O, Ostergaard, SD, Gasse, C. Trends in the psychopharmacological treatment of bipolar disorder: a nationwide register-based study. Acta Neuropsychiatr 2016;28:7584.Google Scholar
Hall, RC, Joffe, JR. Aberrant response to diazepam: a new syndrome. Am J Psychiatry 1972;129:738742.Google Scholar
Michelini, S, Cassano, GB, Frare, F, Perugi, G. Long-term use of benzodiazepines: tolerance, dependence and clinical problems in anxiety and mood disorders. Pharmacopsychiatry 1996;29:127134.Google Scholar
Schepis, TS, Teter, CJ, Simoni-Wastila, L, McCabe, SE. Prescription tranquilizer/sedative misuse prevalence and correlates across age cohorts in the US. Addict Behav 2018;87:2433.Google Scholar
Advisory Council on the Misuse of Drugs. Novel Benzodiazepines. A Review of the Evidence of Use and Harms of Novel Benzodiazepines. April 2020.Google Scholar
Clinical Guidelines on Drug Misuse and Dependence. Update 2017, Independent Expert Working Group. Drug Misuse and Dependence: UK Guidelines on Clinical Management. London, Department of Health, 2017.Google Scholar
Clinical Guidelines on Drug Misuse and Dependence. Update 2017, Independent Expert Working Group. Drug Misuse and Dependence: UK Guidelines on Clinical Management. London, Department of Health, 2017.Google Scholar
Taylor, S, Annand, F, Burkinshaw, P, et al. Dependence and Withdrawal Associated with Some Prescribed Medicines: An Evidence Review. London, Public Health England, 2019.Google Scholar
Fluyau D, Revadigar N, Manobianco BE. Challenges of the pharmacological management of benzodiazepine withdrawal, dependence, and discontinuation. Ther Adv Psychopharmacol 2018;8(5):147–168.Google Scholar
Baandrup, L, Ebdrup, BH, Rasmussen, , Lindschou, J, Gluud, C, Glenthøj, BY. Pharmacological interventions for benzodiazepine discontinuation in chronic benzodiazepine users. Cochrane Database Syst Rev 2018;3:CD011481.Google Scholar
Soyka, M. Treatment of benzodiazepine dependence. N Engl J Med 2017;376:11471157. https://doi.org/10.1056/NEJMra1611832Google Scholar
Baandrup, L, Ebdrup, BH, Rasmussen, , Lindschou, J, Gluud, C, Glenthøj, BY. Pharmacological interventions for benzodiazepine discontinuation in chronic benzodiazepine users. Cochrane Database Syst Rev 2018;3:CD011481. https://doi.org/10.1002/14651858.CD011481.pub2Google Scholar
Denis, C, Fatséas, M, Lavie, E, Auriacombe, M. Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings. Cochrane Database Syst Rev 2006;3:CD005194.Google Scholar
Oulis, P, Konstantakopoulos, G. Efficacy and safety of pregabalin in the treatment of alcohol and benzodiazepine dependence. Expert Opin Investig Drugs 2012;21:10191029.Google Scholar
Hood, SD, Norman, A, Hince, DA, Melichar, JK, Hulse, GK. Benzodiazepine dependence and its treatment with low dose flumazenil. Br J Clin Pharmacol 2014;77:285294.Google Scholar
Lugoboni, F, Faccini, M, Quaglio, G, Albiero, A, Casari R, Pajusco B. Intravenous flumazenil infusion to treat benzodiazepine dependence should be performed in the inpatient clinical setting for high risk of seizure. J Psychopharmacol 2011;25:848849.Google Scholar
Hayhoe, B, Lee-Davey, J. Tackling benzodiazepine misuse. Br Med J 2018;362:k3208. https://doi.org/10.1136/bmj.k3208Google Scholar
Parr, JM, Kavanagh, DJ, Cahill, L, Mitchell, G, Young, RMcD. Effectiveness of current treatment approaches for benzodiazepine discontinuation: a meta-analysis. Addiction 2009;104:1324.Google Scholar
Ten Wolde, GB, Dijkstra, A, van Empelen, P, van den Hout, W, Neven, AK, Zitman, F. Long-term effectiveness of computer-generated tailored patient education on benzodiazepines: a randomized controlled trial. Addiction 2008;103:662670.Google Scholar
Mugunthan, K, McGuire, T, Glasziou, P. Minimal interventions to decrease long-term use of benzodiazepines in primary care: a systematic review and meta-analysis. Br J Gen Pract 2011;61(590):e573e578.Google Scholar
Soyka, M. Treatment of benzodiazepine dependence. N Engl J Med 2017;376:11471157. https://doi.org/10.1056/NEJMra1611832Google Scholar
Lader, M, Tylee, A, Donoghue, J. Withdrawing benzodiazepines in primary care. CNS Drugs 2009;23:1934.Google Scholar

References

Karila L, , Marillier M, , Chaumette B, , Billieux J, , Franchitto N, , Benyamina A., New synthetic opioids: part of a new addiction landscape. Neurosci Biobehav Rev 2019;106:133140.Google Scholar
Stoicea, N, Costa A, , Periel L, , Uribe A, , Weaver T, , Bergese SD. Current perspectives on the opioid crisis in the US healthcare system: a comprehensive literature review. Medicine 2019;98(20):e15425https://doi.org/10.1097/MD.0000000000015425Google Scholar
European School Survey Project on Alcohol and Other Drugs. Published 2015. Available at: www.espad.org/sites/espad.org/files/ESPAD_report_2015.pdf [last accessed 28 February 2022].Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2019: Trends and Developments. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2019: Trends and Developments. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
Pichini, S, Solimini, R, Berretta, P, Pacifici, R, Busardò, FP. Acute intoxications and fatalities from illicit fentanyl and analogues: an update. Ther Drug Monit 2018;40:3851. https://doi.org/10.1097/FTD.0000000000000465Google Scholar
Schifano F, , Chiappini S, , Corkery JM, , Guirguis A., Assessing the 2004–2018 fentanyl misusing issues reported to an international range of adverse reporting systems. Front Pharmacol 2019;10:46.Google Scholar
The United Nations Office on Drugs and Crime (UNODC). World Drug Report 2019 (United Nations publication, Sales No. E.19.XI.8). Available at: https://wdr.unodc.org/wdr2019/prelaunch/WDR19_Booklet_1_EXECUTIVE_SUMMARY.pdf; www.unodc.org/wdr2018/prelaunch/WDR18_Booklet_1_EXSUM.pdf [last accessed 28 February 2022].Google Scholar
Schifano F, , Chiappini S, , Corkery JM, , Guirguis A., Assessing the 2004–2018 fentanyl misusing issues reported to an international range of adverse reporting systems. Front Pharmacol 2019;10:46.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2019: Trends and Developments. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
The United Nations Office on Drugs and Crime (UNODC). World Drug Report 2020 (United Nations publication, Sales No. E.20.XI.6).Google Scholar
United Nations Office on Drugs and Crime (UNODC). Fentanyl and its analogues – 50 years on. Global SMART Update, 2017.Google Scholar
Ayres, WA, Starsiak, MJ, Sokolay, P. The bogus drug: three methyl and alpha methyl fentanyl sold as ‘China White’. J Psychoactive Drugs 1981;13(1):9193.Google Scholar
Higashikawa, Y, Suzuki, S. Studies on 1-(2-phenethyl)-4-(N-propionylanilino) piperidine (fentanyl) and its related compounds. VI. Structure–analgesic activity relationship for fentanyl, methyl-substituted fentanyls and other analogues. Forensic Toxicol 2008;26(1):15. https://doi.org/10.1007/s11419-007-0039–1Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Misuse of Fentanyl and Fentanyl Analogues. January 2020.0Google Scholar
Lemmens, H. Pharmacokinetic-pharmacodynamic relationships for opioids in balanced anaesthesia. Clin Pharmacokinet 1995;29:231242.Google Scholar
Janssen, PA. Potent, new analgesics, tailormade for different purposes. Acta Anaesthesiol Scand 1982;26(3):262268.Google Scholar
Pichini S, , Zaami S, , Pacifici R, , Tagliabracci A, , Busardò FP. The challenge posed by new synthetic opioids: pharmacology and toxicology. Front Pharmacol 2019;10:563.Google Scholar
Pearson J, Poklis J, Poklis A, et al. Post-mortem toxicology findings of acetyl fentanyl, fentanyl, and morphine in heroin fatalities in Tampa, Florida. Acad Forensic Pathol 2015;5(4):676689.Google Scholar
Pompei, P, Micioni Di Bonaventura MV, Cifani C. The ‘legal highs’ of novel drugs of abuse. J Drug Abuse 2016;2:2.Google Scholar
Fairbairn, N, Coffin, PO, Walley, AY. Naloxone for heroin, prescription opioid, and illicitly made fentanyl overdoses: challenges and innovations responding to a dynamic epidemic. Int J Drug Policy 2017;46:172179. https://doi.org/10.1016/j.drugpo.2017.06.005Google Scholar
Armenian, P, Vo, KT, Barr-Walker, J, Lynch, KL. Fentanyl, fentanyl analogs and novel synthetic opioids: a comprehensive review. Neuropharmacology 2017;pii:S0028–3908(17)30484-7. https://doi.org/10.1016/jneuropharm.2017.10.016Google Scholar
Pérez-Mañá C, , Papaseit E, , Fonseca F, , Farré A, , Torrens M, , Farré M., Drug interactions with new synthetic opioids Front Pharmacol 2018 (online). https://doi.org/10.3389/fphar.2018.01145.Google Scholar
Labutin, AV, Temerdashev, AZ, Dukova, OA, et al. Identification of furanoylfentanil and its metabolites in human urine. J Environ Anal Toxicol 2017;7:3. https://doi.org/10.4172/2161-0525.1000456Google Scholar
Zawilska, JB. An expanding world of novel psychoactive substances: opioids. Front Psychiatry 2017;8:110. https://doi.org/10.3389/fpsyt.2017.00110Google Scholar
Pérez-Mañá C, , Papaseit E, , Fonseca F, , Farré A, , Torrens M, , Farré M., Drug interactions with new synthetic opioids Front Pharmacol 2018 (online). https://doi.org/10.3389/fphar.2018.01145.Google Scholar
Pérez-Mañá C, , Papaseit E, , Fonseca F, , Farré A, , Torrens M, , Farré M., Drug interactions with new synthetic opioids Front Pharmacol 2018 (online). https://doi.org/10.3389/fphar.2018.01145.Google Scholar
Daniulaityte, R, Juhascik, MP, Strayer, KE, et al. Overdose deaths related to fentanyl and its analogs – Ohio, JanuaryFebruary 2017. Morb Mortal Wkly Rep 2017;66:904908. https://doi.org/10.15585/mmwr.mm6634a3Google Scholar
Rogers, JS, Rehrer, SJ, Hoot, NR. Acetylfentanyl: an emerging drug of abuse. J Emerg Med 2016;50(3):433436. https://doi.org/10.1016/j.jemermed.2015.10.014Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Report on the Risk Assessment of Nphenyl-N-[1-(2-phenylethyl)piperidin-4-yl]furan-2-carboxamide (Furanylfentanyl) in the Framework of the Council Decision on New Psychoactive Substances. Lisbon, EMCDDA, 2017.Google Scholar
Rojkiewicz, M, Majchrzak, M, Celinski, R, Kus, P, Sajewicz, M. Identification and physicochemical characterization of 4-fluorobutyrfentanyl (1-((4-fluorophenyl)(1- phenethylpiperidin-4-yl)amino)butan-1-one, 4-FBF) in seized materials and postmortem biological samples. Drug Test Anal 2017;9:405414.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Fentanyl drug profile. Available at: www.emcdda.europa.eu/publications/drug-profiles/fentanyl_en [last accessed 23 April 2022].Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). European Drug Report 2017: Trends and Developments. Luxembourg: Publications Office of the European Union, 2017.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2019: Trends and Developments. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
Mounteney, J, Giraudon, I, Denissov, G, Griffiths, P. Fentanyls: are we missing the signs? Highly potent and on the rise in Europe. Int J Drug Pol 2015;26:626631. https://doi.org/10.1016/j.drugpo.2015.04.003Google Scholar
Pichini S, Pacifici R, Marinelli E, Busardò FP. European drug users at risk from illicit fentanyls mix. Front Pharmacol 2017;31:785. https://doi.org/10.3389/fphar. 2017.00785Google Scholar
Pichini, S, Solimini, R, Berretta, P, Pacifici, R, Busardò, FP. Acute intoxications and fatalities from illicit fentanyl and analogues: an update. Ther Drug Monit 2018;40:3851. https://10.1097/FTD.0000000000000465Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2019: Trends and Developments. Publications Office of the European Union, Luxembourg, 2019.Google Scholar
Klar, SA, Brodkin, E, Gibson, E, et al. Notes from the field: furanyl-fentanyl overdose events caused by smoking contaminated crack cocaine – British Columbia, Canada, 15–18 July 2016. Morb Mortal Weekly Rep 2016;65(37):10151016. https://doi.org/10.15585/mmwr.mm6537a6Google Scholar
Frank, RG, Pollack, HA. Addressing the fentanyl threat to public health. N Engl J Med 2017;376(7):605607. https://doi.org/10.1056/NEJMp1615145Google Scholar
Arens, AM, van Wijk, XMR, Vo, KT, et al. Adverse effects from counterfeit alprazolam tablets. JAMA Intern Med 2016;176(10):15541555. https://doi.org/doi:10.1001/jamainternmed.2016.4306Google Scholar
Green, TC, Gilbert, M. Counterfeit medications and fentanyl. JAMA Inter Med 2016;176(10):15551557. https://doi.org/10.1001/jamai- nternmed.2016.4310Google Scholar
Stogner, JM. The potential threat of acetyl fentanyl: legal issues, contaminated heroin, and acetyl fentanyl ‘disguised’ as other opioids. Ann Emerg Med 2014;64(6):637639. https://doi.org/10.1016/j. annemergmed.2014.07.017Google Scholar
Lozier, MJ, Boyd, M, Stanley, C, et al. Acetyl fentanyl, a novel fentanyl analog, causes overdose deaths in Rhode Island, March–May 2013. J Med Toxicol 2015;11:208217. https://doi.org/10.1007/s13181-015-0477-9Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Misuse of Fentanyl and Fentanyl Analogues. January 2020.Google Scholar
Suzuki, J, El-Haddad, S. A review: fentanyl and non-pharmaceutical fentanyls. Drug Alcohol Depend 2016;171:107–116. https://doi.org/10.1016/j. drugalcdep. 2016.11.033Google Scholar
Stanley, TH. The fentanyl story. J Pain 2014;15:12151226. https://doi.org/10.1016/j. jpain.2014.08.010 10Google Scholar
Armenian, P, Olson, A, Anaya, A, et al. Fentanyl and a novel synthetic opioid U-47700 masquerading as street ‘Norco’ in Central California: a case report. Ann Emerg Med 2017;69:8790.Google Scholar
Miller, JM, Stogner, JM, Miller, BL, Blough, S. Exploring synthetic heroin: accounts of acetyl fentanyl use from a sample of dually diagnosed drug offenders. Drug Alcohol Rev 2017;37(1):121127. https://doi.org/10.1111/dar.12502Google Scholar
Amlani, A, McKee, G, Khamis, N, et al. Why the FUSS (Fentanyl Urine Screen Study)? A cross-sectional survey to characterize an emerging threat to people who use drugs in British Columbia, Canada. Harm Reduction J 2015;12:54. https://doi.org/10.1186/s12954-015-0088-4Google Scholar
Ciccarone, D, Ondocsin, J, Mars, S. Heroin uncertainties: exploring users’ perceptions of fentanyl-adulterated and -substituted heroin. Int J Drug Policy 2017;46:146155.Google Scholar
Macmadu, A, Carroll, JJ, Hadland, SE, et al. Prevalence and correlates of fentanyl-contaminated heroin exposure among young adults who use prescription opioids non-medically. Addict Behav 2017;68:3538. https://doi.org/10.1016/j.addbeh.2017.01.014Google Scholar
Prekupec MP, , Mansky PA, , Baumann MH., Misuse of novel synthetic opioids: a deadly new trend. J Addict Med 2017;11:256265.Google Scholar
Gill, H, Kelly, E, Henderson, H. How the complex pharmacology of the fentanyls contributes to their lethality. Addiction 2019 (online). https://doi.org/10.1111/add.14614Google Scholar
McClain, DA, Hug, CC Jr. Intravenous fentanyl kinetics. Clin Pharmacol Ther 1980;28(1):106114.Google Scholar
Siddiqi, S, Verney, C, Dargan, P, et al. Understanding the availability, prevalence of use, desired effects, acute toxicity and dependence potential of the novel opioid MT-45. Clin Toxicol 2015;53(1):5459.Google Scholar
Gladden, RM, Martinez, P, Seth, P. Fentanyl law enforcement submissions and increases in synthetic opioid-involved overdose deaths – 27 states, 2013–2014. Morb Mortal Wkly Rep 2016;65:837843.Google Scholar
Peterson, AB, Gladden, RM, Delcher, C, et al. Increases in fentanyl-related overdose deaths – Florida and Ohio, 2013–2015. Morb Mortal Wkly Rep 2016;65:844849.Google Scholar
United Nations Office on Drugs and Crime Early Warning Advisory. Deaths associated with use of emerging synthetic opioids (News announcement). November 2016.Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Misuse of Fentanyl and Fentanyl Analogues. January 2020.Google Scholar
Gill, H, Kelly, E, Henderson, H. How the complex pharmacology of the fentanyls contributes to their lethality. Addiction 2019 (online). https://doi.org/10.1111/add.14614Google Scholar
Bowdle, TA. Adverse effects of opioid agonists and agonist-antagonists in anaesthesia. Drug Saf 1998;19:173189.Google Scholar
Armenian, P, Vo, KT, Barr-Walker, J, Lynch, KL. Fentanyl, fentanyl analogs and novel synthetic opioids: a comprehensive review. Neuropharmacology 2017;134:121132. https://doi.org/10.1016/j.neuropharm.2017.10.016Google Scholar
Prekupec, MP, Mansky, PA, Baumann, MH. Misuse of novel synthetic opioids: a deadly new trend. J Addict Med 2017;11:256265. https://doi.org/10.1097/ ADM.0000000000000324Google Scholar
Ventura, L, Carvalho, F, Dinis-Oliveira, RJ. Opioids in the frame of new psychoactive substances network: a complex pharmacological and toxicological issue. Curr Mol Pharmacol 2018;11:97108. https://doi.org/10.2174/ 1874467210666170704110146Google Scholar
Solimini, R, Pichini, S, Pacifici, R, Busardò, FP, Giorgetti, R. Pharmatoxicology of non-fentanyl derived new synthetic opioids. Front Pharmacol 2018;9:654. https://doi.org/10.3389/fphar.2018.00654Google Scholar
Kinshella, MW, Gauthier, T, Lysyshyn, M. Rigidity, dyskinesia and other atypical overdose presentations observed at a supervised injection site, Vancouver, Canada. Harm Reduct J 2018;15:64. https://doi.org/10.1186/s12954-018-0271-5Google Scholar
Mayer, S, Boyd, J, Collins, A, Kennedy, MC, Fairbairn, N, McNeil, R. Characterizing fentanyl-related overdoses and implications for overdose response: findings from a 64 rapid ethnographic study in Vancouver, Canada. Drug Alcohol Depend 2018;193:6974. https://doi.org/10.1016/j.drugalcdep.2018.09.006.Google Scholar
Torralva, PR, Janowsky, A. Noradrenergic mechanisms in fentanyl-mediated rapid death explain failure of naloxone in the opioid crisis. J Pharmacol Exp Ther 2019;371 (2):453475. https://doi.org/10.1124/jpet.119.258566Google Scholar
Burns, G, DeRienz, RT, Baker, DD, et al. Could chest wall rigidity be a factor in rapid death from illicit fentanyl abuse? Clin Toxicol 2016;54(5):420423.Google Scholar
Armenian, P, Vo, KT, Barr-Walker, J, Lynch, KL. Fentanyl, fentanyl analogs and novel synthetic opioids: a comprehensive review. Neuropharmacology 2017;134:121132. https://doi.org/10.1016/j.neuropharm.2017.10.016Google Scholar
Somerville, NJ, O’Donnell, J, Gladden, RM, et al. Characteristics of fentanyl overdose – Massachusetts, 2014–2016. Morb Mortal Wkly Rep 2017;66(14):382386.Google Scholar
Prekupec, MP, Mansky, PA, Baumann, MH. Misuse of novel synthetic opioids: a deadly new trend. J Addict Med 2017;11:256265. https://doi.org/10.1097/ ADM.0000000000000324Google Scholar
Ventura, L, Carvalho, F, Dinis-Oliveira, RJ. Opioids in the frame of new psychoactive substances network: a complex pharmacological and toxicological issue. Curr Mol Pharmacol 2018;11:97108. https://doi.org/10.2174/ 1874467210666170704110146Google Scholar
Solimini, R, Pichini, S, Pacifici, R, Busardò, FP, Giorgetti, R. Pharmatoxicology of non-fentanyl derived new synthetic opioids. Front Pharmacol 2018;9:654. https://doi.org/10.3389/fphar.2018.00654Google Scholar
Cole, JB, Dunbar, JF, McIntire, SA, et al. Butyrfentanyl overdose resulting in diffuse alveolar hemorrhage. Pediatrics 2015;235(3). https://doi.org/10.1542/peds.2014-2878Google Scholar
Ruzycki, S, Yarema, M, Dunham, M, et al. Intranasal fentanyl intoxication leading to diffuse alveolar hemorrhage. J Med Toxicol 2016;12(1):185188.Google Scholar
Kucuk, HO, Kucuk, U, Kolcu, Z, et al. Misuse of fentanyl transdermal patch mixed with acute coronary syndrome. Hum Exp Toxicol 2016;35(1):5152.Google Scholar
Duru, UB, Pawar, G, Barash, JA, et al. An unusual amnestic syndrome associated with combined fentanyl and cocaine use. Ann Intern Med 2018 (online). https://doi.org/10.7326/L17-0575Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Cyclopropylfentanyl. EMCDDA–Europol Joint Report on a new psychoactive substance: N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl] cyclopropanecarboxamide (cyclopropylfentanyl). Available at: www.emcdda.europa.eu/system/files/publications/7926/20181014_TDAS18001ENN_PDF.pdf [last accessed 23 April 2022].Google Scholar
Pérez-Mañá C, , Papaseit E, Fonseca F, Farré A, Torrens M, Farré M. Drug interactions with new synthetic opioids. Front Pharmacol 2018 (online). https://doi.org/10.3389/fphar.2018.01145Google Scholar
Helander, A, Bäckberg, M, Signell, P, Beck, O. Intoxications involving acrylfentanyl and other novel designer fentanyls – results from the Swedish STRIDA project. Clin Toxicol 2017;55(6):589599.Google Scholar
Pichini, S, Solimini, R, Berretta, P, et al. Acute intoxications and fatalities from illicit fentanyl and analogues: an update. Ther Drug Monit 2018;40(1):3851. https://doi.org/10.1097/FTD.0000000000000465Google Scholar
Roxburgh, A, Burns, L, Drummer, OH, et al. Trends in fentanyl prescriptions and fentanyl-related mortality in Australia. Drug Alcohol Rev 2013;32(3):269275.Google Scholar
Rodda, LN, Pilgrim, JL, Di Rago, M, et al. A cluster of fentanyl-laced heroin deaths in 2015 in Melbourne, Australia. Anal Toxicol 2017;41(4):318324. https://doi.org/10.1093/jat/bkx013Google Scholar
Guerrieri, D, Roman, M, Thelander, G, Kronstrand, R. Acrylfentanyl: another new psychoactive drug with fatal consequences. Forensic Sci Int 2017;277:e21e29. https://doi.org/10.1016/j.forsciint.2017.05.010Google Scholar
Rudd, RA, Seth, P, David, F, et al. Increases in drug and opioid-involved overdose deaths: United States, 2010–2015. Morb Mortal Wkly Rep 2016;65:14451452.Google Scholar
Warner, M, Chen, LH, Makuc, DM, et al. Drug Poisoning Deaths in the United States, 1980–2008 (NCHS Data Brief, No. 81). Hyattsville, MD, National Center for Health Statistics, 2011. Available at www.cdc.gov/nchs/products/databriefs/db81.htm [last accessed 28 February 2022].Google Scholar
Chen, LH, Hedegaard, H, Warner, M. Drug-poisoning Deaths Involving Opioid Analgesics: United States, 1999–2011 (NCHS Data Brief, No. 166). Hyattsville, MD, National Center for Health Statistics, 2014. Available at: www.cdc.gov/nchs/products/databriefs/db166.htm [last accessed 28 February 2022].Google Scholar
Hedegaard, H, Chen, LH, Warner, M. Drug-poisoning Deaths Involving Heroin: United States, 2000–2013 (NCHS Data Brief, No. 190). Hyattsville, MD: National Center for Health Statistics, 2015. Available at: www.cdc.gov/nchs/products/databriefs/db190.htm [last accessed 28 February 2022].Google Scholar
National Center for Health Statistics. Public-use Data Files: Mortality Multiple Cause Files, 2015.Google Scholar
Centre for Disease Control and Prevention. Synthetic Opioid Data Excluding Methadone but Including Drugs Like Tramadol and Fentanyl.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Europol. Joint Report on a New Psychoactive Substance: 2-methoxy-N-phenyl-N-[1-(2-phenylethyl) piperidin-4-yl]acetamide (methoxyacetylfentanyl). Available at: www.emcdda.europa.eu/system/files/publications/7925/20181015_TDAS18002ENN_PDF.pdf [last accessed 28 February 2022].Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Europol. Joint Report on a New Psychoactive Substance: N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl] cyclopropanecarboxamide (cyclopropylfentanyl). Available at: www.emcdda.europa.eu/system/files/publications/7926/20181014_TDAS18001ENN_PDF.pdf [last accessed 28 February 2022].Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Prevention of Drug-related Deaths. Available at: www.emcdda.europa.eu/publications/topic-overviews/prevention-drug-related-deaths [last accessed 28 February 2022].Google Scholar
Drummer OH., Fatalities caused by novel opioids: a review. Forensic Sci Res 2019;4(2):95110. https://doi.org/10.1080/20961790.2018.1460063Google Scholar
Lovrecic B, , Lovrecic M, , Gabrovec B, , et al. Non-medical use of novel synthetic opioids: a new challenge to public health. Int. J. Environ. Res. Public Health 2019;16:177. https://doi.org/10.3390/ijerph16020177Google Scholar
Drummer OH., Fatalities caused by novel opioids: a review. Forensic Sci Res 2019;4(2):95110. https://doi.org/10.1080/20961790.2018.1460063Google Scholar
Lovrecic B, , Lovrecic M, , Gabrovec B, , et al. Non-medical use of novel synthetic opioids: a new challenge to public health. Int J Environ Res Public Health 2019;16:177. https://doi.org/10.3390/ijerph16020177Google Scholar
Drummer OH., Fatalities caused by novel opioids: a review. Forensic Sci Res 2019;4(2):95110. https://doi.org/10.1080/20961790.2018.1460063Google Scholar
Lovrecic B, , Lovrecic M, , Gabrovec B, , et al. Non-medical use of novel synthetic opioids: a new challenge to public health. Int J Environ Res Public Health 2019;16:177. https://doi.org/10.3390/ijerph16020177Google Scholar
Hull, MJ, Juhascik, M, Mazur, F, et al. Fatalities associated with fentanyl and co-administered cocaine or opiates. J Forensic Sci 2007;52:13831388.Google Scholar
Drummer OH., Fatalities caused by novel opioids: a review. Forensic Sci Res 2019;4(2):95110. https://doi.org/10.1080/20961790.2018.1460063Google Scholar
Ojanpera, I, Gergov, M, Liiv, M, et al. An epidemic of fatal 3-methylfentanyl poisoning in Estonia. Int J Legal Med 2008;122:395400.Google Scholar
Marinetti, LJ, Ehlers, BJ. A series of forensic toxicology and drug seizure cases involving illicit fentanyl alone and in combination with heroin, cocaine or heroin and cocaine. J Anal Toxicol 2014;38:592598.Google Scholar
National Center for Biotechnology Information. PubChem Compound Summary for CID 62156, Carfentanil. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Carfentanil [last accessed1March2022].Google Scholar
Lovrecic B, , Lovrecic M, , Gabrovec B, , et al. Non-medical use of novel synthetic opioids: a new challenge to public health. Int J Environ Res Public Health 2019;16:177. https://doi.org/10.3390/ijerph16020177Google Scholar
Bäckberg, M, Beck, O, Jönsson, K-H, Helander, A. Opioid intoxications involving butyrfentanyl, 4-fluorobutyrfentanyl, and fentanyl from the Swedish STRIDA project. Clin Toxicol 2015;53(7):609617. https://doi.org/10.3109/15563650.2015.1054505Google Scholar
McIntyre, IM, Anderson, DT. Post-mortem fentanyl concentrations: a review. J Forensic Res 2012;3:157.Google Scholar
Latimer, J, Ling, S, Flaherty, I, et al. Risk of fentanyl overdose among clients of the Sydney Medically Supervised Injecting Centre. Int J Drug Policy 2016;37:111114.Google Scholar
Darke, S, Duflou, J. The toxicology of heroin-related death: estimating survival times. Addiction 2016;111(9):16071613. https://doi.org/10.1111/ add.13429Google Scholar
Kim HK, , Connors NJ, , Mazer-Amirshahi ME., The role of take-home naloxone in the epidemic of opioid overdose involving illicitly manufactured fentanyl and its analogs. Expert Opin Drug Saf 2019(online). https://doi.org/10.1080/14740338.2019.1613372Google Scholar
Henderson, GL. Fentanyl-related deaths: demographics, circumstances, and toxicology of 112 cases. J Forensic Sci 1991;36(2):422433.Google Scholar
Woodall, KL, Martin, TL, McLellan, BA. Oral abuse of fentanyl patches (Duragesic®): seven case reports. J Forensic Sci 2008;53(1):222225. https://doi.org/10.1111/j.1556-4029.2007.00597.xGoogle Scholar
O’Donnell, JK, Halpin, J, Mattson, CL, et al. Deaths involving fentanyl, fentanyl analogs, and u-47700 – 10 states, July–December 2016. Morb Mortal Wkly Rep 2017;66(43):11971202. https://doi.org/10.15585/mmwr.mm6643e1Google Scholar
Gomes, T, Juurlink, DN, Mamdani, MM, et al. Prevalence and characteristics of opioid-related deaths involving alcohol in Ontario, Canada. Drug Alcohol Depend 2017;179:416423.Google Scholar
Pérez-Mañá, C, Papaseit, E, Fonseca, F, Farré, A, Torrens, M, Farré, M. Drug interactions with new synthetic opioids. Front Pharmacol 2018 (online). | https://doi.org/10.3389/fphar.2018.01145Google Scholar
Pérez-Mañá C, , Papaseit E, , Fonseca F, , Farré A, , Torrens M, , Farré M., Drug interactions with new synthetic opioids. Front Pharmacol 2018 (online). https://doi.org/10.3389/fphar.2018.01145Google Scholar
Atkinson, TJ, Fudin, J. Interactions between pain medications and illicit street drugs. Pract Pain Manag 2014;7:14.Google Scholar
Mozayani, A, Raymon, LP. Handbook of Drug Interactions. New Jersey, NJ, Humana Press Inc., 2004. https://doi.org/10.1007/978-1-59259-654-6Google Scholar
Pérez-Mañá C, , Papaseit E, , Fonseca F, , Farré A, , Torrens M, , Farré M., Drug interactions with new synthetic opioids. Front Pharmacol 2018 (online). https://doi.org/10.3389/fphar.2018.01145Google Scholar
Rickli, A, Liakoni, E, Hoener, MC, Liechti, ME. Opioid-induced inhibition of the human 5-HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome. Br J Pharmacol 2018;175:532543. https://doi.org/10.1111/bph.14105Google Scholar
Greenier, E, Lukyanova, V, Reede, L. Serotonin syndrome: fentanyl and selective serotonin reuptake inhibitor interactions. AANA J 2014;82(5):340345.Google Scholar
National Institute for Health and Care Excellence. Fentanyl interactions. Available at: https://bnf.nice.org.uk/interaction/fentanyl-2.html?msclkid=fc39a64bc2f311ecb6896b20054e84be [last accessed 23 April 2022].Google Scholar
World Health Organization Expert Committee on Drug Dependence, thirty-ninth report. Geneva, WHO, 2018 (WHO Technical Report Series, No. 1009). License: CC BY-NC-SA 3.0 IGO.Google Scholar
World Health Organization. Community Management of Opioid Overdose, 2014. Available at: https://apps.who.int/iris/bitstream/handle/10665/137462/9789241548816_eng.pdf;jsessionid=F58F5BF19670B076BDF8B483B062C22F?sequence=1 [last accessed 1 March 2022].Google Scholar
Strang, J, McDonald, R. Preventing Opioid Overdose Deaths with Take-Home Naloxone. Publications Office of the European Union, Luxembourg. 2016. Available at: www.emcdda.europa.eu/system/files/publications/2089/TDXD15020ENN.pdf [last accessed 1 March 2022].Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. Take-Home Naloxone. Available at: www.emcdda.europa.eu/publications/topic-overviews/take-home-naloxone_en [last accessed 1 March 2022].Google Scholar
Advisory Council on the Misuse of Drugs. Misuse of Fentanyl and Fentanyl Analogues 2020. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/855893/ACMD_Report_-_Misuse_of_fentanyl_and_fentanyl_analogues.pdf [last accessed 1 March 2022].Google Scholar
World Health Organization. Community Management of Opioid Overdose Guideline, 2014. Available at: www.who.int/publications/i/item/9789241548816 [last accessed 23 April 2022].Google Scholar
Advisory Council on the Misuse of Drugs. Misuse of Fentanyl and Fentanyl Analogues. January 2020.Google Scholar
Mayer, S, Boyd, J, Collins, A, Kennedy, MC, Fairbairn, N, McNeil, R. Characterizing fentanyl-related overdoses and implications for overdose response: findings from a 64 rapid ethnographic study in Vancouver, Canada. Drug Alcohol Depend 2018;193:6974. https://doi.org/10.1016/j.drugalcdep.2018.09.006.Google Scholar
Advisory Council on the Misuse of Drugs. Misuse of Fentanyl and Fentanyl Analogues. January 2020.Google Scholar
Lynn, RR, Galinkin, JL. Naloxone dosage for opioid reversal: current evidence and clinical implications. Ther Adv Drug Saf 2018;9(1):6388. https://doi.org/10.1177/2042098617744161Google Scholar
Advisory Council on the Misuse of Drugs. Misuse of Fentanyl and Fentanyl Analogues. January 2020.Google Scholar
Strang, J, McDonald, R (eds). Preventing Opioid Overdose Deaths with Take-Home Naloxone. Luxembourg, EMCDDA, 2016. Available at: www.emcdda.europa.eu/system/files/publications/2089/TDXD15020ENN.pdf [last accessed 23 April 2022].Google Scholar
Advisory Council on the Misuse of Drugs. Misuse of Fentanyl and Fentanyl Analogues. January 2020.Google Scholar
Moss RB, , Carlo DJ. Higher doses of naloxone are needed in the synthetic opioid era. Subst Abuse Treat Prev Policy 2019;14:6. https://doi.org/10.1186/s13011-019-0195-4Google Scholar
Lucyk, SN, Nelson, LS. Novel synthetic opioids: an opioid epidemic within an opioid epidemic. Ann Emerg Med 2017;69(1):9193. https://doi.org/10.1016/j.annemergmed.2016.08.445Google Scholar
Ramos-Matos, C, López-Ojeda W. China White: clinical insights of an evolving designer underground drug. Universal J Clin Med 2015;3(1):69. https://doi.org/10.13189/ujcm.2015.030102Google Scholar
Neale, J, Strang, J. Naloxone – does over-antagonism matter? Evidence of iatrogenic harm after emergency treatment of heroin/opioid overdose. Addiction 2015;110(10):16441652. https://doi.org/10.1111/add.13027Google Scholar
Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence (2009). Available at: www.who.int/publications/i/item/9789241547543?msclkid=6d2b2cadc2f511ec84abaff20e8ad971; WHO: Community management of opioid overdose 2014. Available at: https://apps.who.int/iris/bitstream/handle/10665/137462/9789241548816_eng.pdf [last accessed 23 April 2022].Google Scholar
Strang J, McDonald R (eds). Preventing Opioid Overdose Deaths with Take-Home Naloxone. EMCDDA, 2016. Available at: www.emcdda.europa.eu/system/files/publications/2089/TDXD15020ENN.pdf [last accessed 23 April 2022].Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Take-Home Naloxone. Available at: www.emcdda.europa.eu/publications/topic-overviews/take-home-naloxone_en [last accessed 1 March 2022].Google Scholar
Strang, J, McDonald, R, Campbell, G, et al. Take-home naloxone for the emergency interim management of opioid overdose: the public health application of an emergency medicine. Drugs 2019;79:13951418. https://doi.org/10.1007/s40265-019-01154-5Google Scholar
Kim HK, Connors NJ, Mazer-Amirshahi ME. The role of take-home naloxone in the epidemic of opioid overdose involving illicitly manufactured fentanyl and its analogs. Expert Opin Drug Saf 2019 (online). https://doi.org/10.1080/14740338.2019.1613372Google Scholar
Schumann, H, Erickson, T, Thompson, TM, et al. Fentanyl epidemic in Chicago, Illinois and surrounding Cook County. Clin Toxicol (Phila) 2008;46:501506.Google Scholar
Peipera NC, Duhart Clarke S, , Vincent LB, , Ciccarone D, , Krala AH, , Zibbella JE. Fentanyl test strips as an opioid overdose prevention strategy: findings from a syringe services program in the Southeastern United States. Int J Drug Policy 2019;63:122128.Google Scholar
Goldman, JE, Waye, KM, Periera, KA, et al. Perspectives on rapid fentanyl test strips as a harm reduction practice among young adults who use drugs: a qualitative study. Harm Reduct J 2019;16:3. https://doi.org/10.1186/s12954-018-0276-0Google Scholar
Green, TC, Park, Nyeong J et al., MI An assessment of the limits of detection, sensitivity and specificity of three devices for public health-based drug checking of fentanyl in street-acquired samples. Int J Drug Policy 2020;77:102661.Google Scholar
Willman, MW, Liss, DB, Schwarz, ES, et al. Do heroin overdose patients require observation after receiving naloxone? Clin Toxicol 2017;55(2):8187.Google Scholar
Cicero, TJ, Ellis, MS, Kasper, ZA. Increases in self-reported fentanyl use among a population entering drug treatment: the need for systematic surveillance of illicitly manufactured opioids. Drug Alcohol Depend 2017;177:101103. https://doi.org/10.1016/j.drugalcdep.2017.04.004Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. Estonia, Country Drug Report 2017. Luxembourg, Publications Office of the European Union, 2017.Google Scholar
Allan, J, Herridge, N, Griffiths, P, et al. Illicit fentanyl use in rural Australia – an exploratory study. J Alcohol Drug Depend 2015;3:196. https://doi.org/10.4172/23296488.1000196Google Scholar
Gecici, O, Gokmen, Z, Nebioglu, M. Fentanyl dependence caused by the non-medical use: a case report. Klinik Psikofarmakoloji Bülteni-Bull Clin Psychopharmacol 2010;20(3):255257. https://doi.org/10.1080/10177833.2010.11790668Google Scholar
Ossipov, MH, Lai, J, King, T, et al. Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure. Biopolymers 2005;80(2–3):319324.Google Scholar
Benyamin, R, Trescot, AM, Datta, S, et al. Opioid complications and side effects. Pain Physician 2008;11(2 Suppl.):S105S120.Google Scholar
Ballantyne, JC. ‘Safe and effective when used as directed’: the case of chronic use of opioid analgesics. J Med Toxicol 2012;8(4):417423.Google Scholar
Solomon, DH, Rassen, JA, Glynn, RJ, et al. The comparative safety of opioids for nonmalignant pain in older adults. Arch Intern Med 2010;170(22):19791986.Google Scholar
Firestone, M, Goldman, B, Fischer, B. Fentanyl use among street drug users in Toronto, Canada: behavioural dynamics and public health implications. Int J Drug Policy 2009;20(1):9092. https://doi.org/10.1016/j.drugpo.2008.02.016Google Scholar
United Nations Office on Drugs and Crime (UNODC). World Drug Report 2017. Vienna, UNODC, 2017.Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Misuse of Fentanyl and Fentanyl Analogues. January 2020.Google Scholar
Solimini, R, Pichini, S, Pacifici, R, Busardò, FP, Giorgetti, R. Pharmatoxicology of non-fentanyl derived new synthetic opioids. Front Pharmacol 2018;9:654. https://doi.org/10.3389/fphar.2018.00654Google Scholar
Pérez-Mañá C, , Papaseit E, Fonseca F, Farré, Torrens M, Farré M. Drug interactions with new synthetic opioids. Front Pharmacol 2018 (online). https://doi.org/10.3389/fphar.2018.01145Google Scholar
Pérez-Mañá C, , Papaseit E, Fonseca F, Farré, Torrens M, Farré M. Drug interactions with new synthetic opioids. Front Pharmacol 2018 (online). https://doi.org/10.3389/fphar.2018.01145Google Scholar
Karinen, R, Tuv, SS, Rogde, S, et al. Lethal poisonings with AH-7921 in combination with other substances. Forensic Sci Int 2014;244:e21e24.Google Scholar
Hayers, AG, Tyers, MB. Determination of receptors that mediate opiate side effects in the mouse. Br J Pharmacol 1983;79:731736. https://doi.org/10.1111/ j.1476-5381.1983.tb10011.xGoogle Scholar
Ciccarone, D. Fentanyl in the US heroin supply: a rapidly changing risk environment. Int J Drug Policy 2017;46:107111. https://doi.org/10.1016/j.drugpo.2017.06.010Google Scholar
Lovrecic B, , Lovrecic M, , Gabrovec B, et al. Non-medical use of novel synthetic opioids: a new challenge to public health. Int J Environ Res Public Health 2019;16:177. https://doi.org/10.3390/ijerph16020177Google Scholar
Cheney, BV, Szmuszkovicz, J, Lahti, RA, Zichi, DA. Factors affecting binding of trans-N-[2-(methylamino) cyclohexyl]benzamides at the primary morphine receptor. J Med Chem 1985;28:18531864.Google Scholar
Harper, NJ, Veitch, GB, Wibberley, DG. 1-(3,4-dichlorobenzamidomethyl)cyclohexyldimethylamine and related compounds as potential analgesics. J Med Chem 1974;17:11881193.Google Scholar
Papsun, D, Krywanczyk, A, Vose, JC, et al. Analysis of MT-45, a novel synthetic opioid, in human whole blood by LC–MS-MS and its identification in a drug-related death. J Anal Toxicol 2016;40(4):313317. https://doi.org/10.1093/jat/bkw012Google Scholar
Helander, A, Bäckberg, M, Beck, O. MT-45, a new psychoactive substance associated with hearing loss and unconsciousness. Clin Toxicol 2014;52(8):901904.Google Scholar
Katselou, M, Papoutsis, I, Nikolaou, P, Spiliopoulou, C, Athanaselis, S. AH-7921: the list of new psychoactive opioids is expanded. Forensic Toxicol 2015;33(2):195201.Google Scholar
Coppola, M, Mondola, R. AH-7921: from potential analgesic medicine to recreational drug. Int J High Risk Behav Addict 2017;6(2):e22593https://doi.org/10.5812/ijhrba.22593Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Technical report on 3,4-dichloro-N-{[1- (dimethylamino)cyclohexyl]methyl}benzamide (AH-7921). Lisbon, EMCDDA, April 2014.Google Scholar
Tabarra I, , Soares S, , Rosado T, et al. Novel synthetic opioids – toxicological aspects and analysis. Forensic Sci Res 2019;4(2):111140. https://doi.org/10.1080/20961790.2019.1588933Google Scholar
European Monitoring Centre for Drugs and Drug Addiction. EMCDDA–Europol Joint Report on a New Psychoactive Substance: AH-7921. Luxembourg, Publications Office of the European Union, 2016. Available at: www.emcdda.europa.eu/publications/joint-report/AH-7921_en [last accessed 23 April 2022].Google Scholar
Uchiyama, N, Matsuda, S, Kawamura, M, et al. Two new-type cannabimimetic quinolinyl carboxylates, QUPIC and QUCHIC, two new cannabimimetic carboxamide derivatives, ADB-FUBINACA and ADBICA, and five synthetic cannabinoids detected with a thiophene derivative a-PVT and an opioid receptor agonist AH-7921 identified in illegal products. Forensic Toxicol 2013;31:223240.Google Scholar
Prekupec, MP, Mansky, PA, Baumann, MH. Misuse of novel synthetic opioids: a deadly new trend. J Addict Med 2017;11(4):256265. https://doi.org/10.1097/ADM.0000000000000324Google Scholar
Uchiyama, N, Matsuda, S, Kawamura, M, et al. Identification of two new-type designer drugs, piperazine derivative MT-45 (I-C6) and synthetic peptide noopept (GVS-111), with synthetic cannabinoid A-834735, cathinone derivative 4-methoxy-alpha-PVP, and phenethylamine derivative 4-methylbuphedrine from illegal products. Forensic Toxicol 2014;32:918.Google Scholar
Kjellgren, A, Jacobsson, K, Soussan, C. The quest for well-being and pleasure: experiences of the novel synthetic opioids AH-7921 and MT-45, as reported by anonymous users online. J Addict Res Ther 2016;7(287):2.Google Scholar
Elliott, S, Brandt, S, Smith, C. The first reported fatality associated with the synthetic opioid 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-Nmethylbenzamide (U-47700) and implications for forensic analysis. Drug Test Anal 16-0092–R1https://doi.org/10.1002/dta.1984Google Scholar
Kjellgren, A, Jacobsson, K, Soussan, C. The quest for well-being and pleasure: experiences of the novel synthetic opioids AH-7921 and MT-45, as reported by anonymous users online. J Addict Res Ther 2016;7(287):2.Google Scholar
Soussan, C, Kjellgren, A. The users of novel psychoactive substances: online survey about their characteristics, attitudes and motivations. Int J Drug Policy 2016;32:7784.Google Scholar
Tabarra I, , Soares S, , Rosado T, et al. Novel synthetic opioids – toxicological aspects and analysis Forensic Sci Res 2019;4(2):111140. https://doi.org/10.1080/20961790.2019.1588933Google Scholar
Katselou, M, Papoutsis, I, Nikolaou, P, et al. AH-7921: the list of new psychoactive opioids is expanded. Forensic Toxicol 2015;33:195201. https://doi.org/10.1007/s11419-015-0271-zGoogle Scholar
Kjellgren, A, Jacobsson, K, Soussan, C. The quest for well-being and pleasure: experiences of the novel synthetic opioids AH-7921 and MT-45, as reported by anonymous users online. J Addict Res Ther 2016;7:287. https://doi.org/10.4172/2155-6105.1000287Google Scholar
Kjellgren, A, Jacobsson, K, Soussan, C. The quest for well-being and pleasure: experiences of the novel synthetic opioids AH-7921 and MT-45, as reported by anonymous users online. J Addict Res Ther 2016;7:287. https://doi.org/10.4172/2155-6105.1000287Google Scholar
Mohr, ALA, Friscia, M, Papsun, D, et al. Analysis of novel synthetic opioids U-47700, U-50488 and furanyl fentanyl by LC–MS/MS in post-mortem casework. J Anal Toxicol 2016;40:709717. https://doi.org/10.1093/jat/bkw086Google Scholar
Elliott, SP, Brandt, SD, Smith, C. The first reported fatality associated with the synthetic opioid 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-Nmethylbenzamide (U-47700) and implications for forensic analysis. Drug Test Anal 2016;8:875879. https://doi.org/10.1002/dta.1984Google Scholar
Kronstrand, R, Thelander, G, Lindstedt, D, Roman, M, Kugelberg, FC. Fatal intoxications associated with the designer opioid AH-7921. J Anal Toxicol 2014;38(8):599604.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Technical report on 3,4-dichloro-N-{[1- (dimethylamino)cyclohexyl]methyl}benzamide (AH-7921). Lisbon, EMCDDA, April 2014.Google Scholar
Hayes, AG, Tyers, MB. Determination of receptors that mediate opiate side effects in the mouse. Br J Pharmacol ;79:731736.Google Scholar
Elliott S, Brandt S, Smith C. The first reported fatality associated with the synthetic opioid 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-Nmethylbenzamide (U-47700) and implications for forensic analysis. Drug Test Anal 16- 0092-R1. https://doi.org/10.1002/dta.1984Google Scholar
Coppola, M, Mondola, R. AH-7921: from potential analgesic medicine to recreational drug. Int J High Risk Behav Addict 2017;6(2):e22593https://doi.org/10.5812/ijhrba.22593Google Scholar
Tabarra I, , Soares S, , Rosado T, et al. Novel synthetic opioids – toxicological aspects and analysis. Forensic Sci Res 2019;4(2):111140. https://doi.org/10.1080/20961790.2019.1588933Google Scholar
Hayes, AG, Tyers, MB. Determination of receptors that mediate opiate side effects in the mouse. Br J Pharmacol 1983;79:731736.Google Scholar
Coppola, M, Mondola R. AH-7921: a new synthetic opioid of abuse. Drug Alcohol Rev 2015;34:109110.Google Scholar
Coppola, M, Mondola R. MT-45: a new, dangerous legal high. J Opioid Management 2014;10:301302.Google Scholar
Nakamura, H, Shimizu, M. Comparative study of 1-cyclohexyl-4-(1,2-diphenylethyl)-piperazine and its enantiomorphs on analgesic and other pharmacological activities in experimental animals. Arch Int Pharmacodyn Thér 1976;221:105121.Google Scholar
Armenian, P, Vo, KT, Barr-Walker, J, Lynch, KL. Fentanyl, fentanyl analogs and novel synthetic opioids: a comprehensive review. Neuropharmacology 2017;134:121132. https://doi.org/10.1016/j.neuropharm.2017.10.016Google Scholar
Prekupec, MP, Mansky, PA, Baumann, MH. Misuse of novel synthetic opioids: a deadly new trend. J Addict Med 2017;11:256265. https://doi.org/10.1097/ ADM.0000000000000324Google Scholar
Ventura, L, Carvalho, F, Dinis-Oliveira, RJ. Opioids in the frame of new psychoactive substances network: a complex pharmacological and toxicological issue. Curr Mol Pharmacol 2018;11:97108. https://doi.org/10.2174/ 1874467210666170704110146Google Scholar
Solimini, R, Pichini, S, Pacifici, R, Busardò, FP, Giorgetti, R. Pharmatoxicology of non-fentanyl derived new synthetic opioids. Front Pharmacol 2018;9:654. https://doi.org/10.3389/fphar.2018.00654Google Scholar
Helander, A, Bradley, M, Hasselblad, A, et al. Acute skin and hair symptoms followed by severe, delayed eye complications in subjects using the synthetic opioid MT-45. Br J Dermatol 2017;176:10211027.Google Scholar
Tabarra I, , Soares S, , Rosado T, et al. Novel synthetic opioids – toxicological aspects and analysis. Forensic Sci Res 2019;4(2):111140. https://doi.org/10.1080/20961790.2019.1588933Google Scholar
Vorce, SP, Knittel, JL, Holler, JM, et al. A fatality involving AH-7921. J Analyt Toxicol 2014;38:226230. https://doi.org/10.1093/jat/bku011Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Drugs in Focus 2011.Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). ACMD’s Recommendation on the Synthetic Opiate AH-7921. London, ACMD, 2014.Google Scholar
Elliott, S, Evans, J. A 3-year review of new psychoactive substances in casework. Forensic Sci Int 2014;243:5560. https://doi.org/10.1016/j.forsciint.2014.04.017Google Scholar
Soh, YNA, Elliott, S. An investigation of the stability of emerging new psychoactive substances. Drug Test Anal 2014;6(78):696704. https://doi.org/10.1002/dta.1576Google Scholar
Kronstrand, R, Thelander, G, Lindstedt, D, et al. Fatal intoxications associated with the designer opioid AH-7921. J Anal Toxicol 2014;38:599604. https://doi.org/10.1093/jat/bku057Google Scholar
Fels H, , Lottner-Nau S, , Sax T, , Roider G, , Graw M, . Postmortem concentrations of the synthetic opioid U-47700 in 26 fatalities associated with the drug. Forensic Sci Int 2019;301:e20–e28. https://doi.org/10.1016/j.forsciint.2019.04.010Google Scholar
Kriikku P, Pelander A, Rasanen I, Ojanperä I. Toxic lifespan of the synthetic opioid U-47,700 in Finland verified by re-analysis of UPLC-TOF-MS data. Forensic Sci Int 2019;300:85–88. https://doi.org/10.1016/j.forsciint.2019.04.030Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Report on the Risk Assessment of MT-45 in the Framework of the Council Decision on New Psychoactive Substances. Luxembourg, Publications Office of the European Union, 2015. Available at: www.emcdda.europa.eu/system/files/publications/1865/TDAK14006ENN.pdf [last accessed 23 April 2022].Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). EMCDDA–Europol Joint Report on a New Psychoactive Substance: 1-cyclohexyl-4-(1,2- diphenylethyl)piperazine (‘MT-45’). Luxembourg, Publications Office of the European Union, 2014. Available at: www.emcdda.europa.eu/publications/joint-reports/MT-45_en [last accessed 23 April 2022].Google Scholar
Ruan, X, Chiravuri, S, Kaye, AD. Comparing fatal cases involving U-47700. Forensic Sci Med Pathol 2016;12:369371.Google Scholar
Jones, MJ, Hernandez, BS, Janis, GC, et al. A case of U-47700 overdose with laboratory confirmation and metabolite identification. Clin Toxicol (Phila) 2017;55:5559.Google Scholar
Coopman, V, Blanckaert, P, Van Parys, G, Van Calenbergh, S, Cordonnier, J. A case of acute intoxication due to combined use of fentanyl and 3,4-dichloro-N-[2-(dimethylamino) cyclohexyl]-N-methylbenzamide (U-47700). Forensic Sci Int 2016;266:6872. https://doi.org/10.1016/j.forsciint.2016.05.001Google Scholar
Papsun, D, Krywanczyk, A, Vose, JC, Bundock, EA, Logan, BK. Analysis of MT-45, a novel synthetic opioid, in human whole blood by LC–MS–MS and its identification in a drug-related death. J Anal Toxicol 2016;40:313317. https://doi.org/10.1093/jat/bkw012Google Scholar
Lucyk, SN, Nelson, LS. Novel synthetic opioids: an opioid epidemic within an opioid epidemic. Ann Emerg Med 2017;69:9193. https://doi.org/10.1016/j.annemergmed.2016.08.445Google Scholar
Armenian, P, Olson, A, Anaya, A, Kurtz, A, Ruegner, R, Gerona, RR. Fentanyl and a novel synthetic opioid U-47700 masquerading as street ‘Norco’ in Central California: a case report. Ann Emerg Med 2017;69:8790. https://doi.org/10.1016/j.annemergme d.2016.06.014Google Scholar
Brittain, RT, Kellett, DN, Neat, ML, et al. Anti-nociceptive effects in N-substituted cyclohexylmethylbenzamides. Br J Pharmacol 1973;49:158159.Google Scholar
Tabarra I, , Soares S, , Rosado T, et al. Novel synthetic opioids – toxicological aspects and analysis. Forensic Sci Res 2019;4(2):111140. https://doi.org/10.1080/20961790.2019.1588933Google Scholar

References

World Drug Report 2019 (United Nations publication, Sales No. E.19.XI.8).Google Scholar
Craig CL, , Loeffler GH., The ketamine analog methoxetamine: a new designer drug to threaten military readiness. Mil Med 2014;179(10):1149.Google Scholar
Zukin, SR, Sloboda, ZJ, Daniel, C. Phencyclidine (PCP). In: Substance Abuse: A Comprehensive Textbook, 4th ed., pp. 324335. Edited by Lowinson, JH, Ruiz, P, Millmann, B, et al. Philadelphia, PA, Lippincott Williams & Wilkins, 1994.Google Scholar
World Drug Report 2019 (United Nations publication, Sales No. E.19.XI.8).Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). European Drug Report 2019: Trends and Developments. Luxembourg, Publications Office of the European Union, 2019.Google Scholar
Van Hout, Hearne E., MWord of mouse’: indigenous harm reduction and online consumerism of the synthetic compound methoxphenidine. J Psychoactive Drugs 2015;47(1):3041. https://doi.org/10.1080/02791072.2014.974002Google Scholar
Bäckberg M, , Beck O, , Helander A., Phencyclidine analog use in Sweden: intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project. Clin Toxicol 2015;53(9):856864. https://doi.org/10.3109/15563650.2015.1079325Google Scholar
See also Wallach, JB, Simon D. Phencyclidine-based new psychoactive substances. Handb Exp Pharmacol 2018;252:261303.Google Scholar
Berger, ML, Schweifer, A, Rebernik, P, Hammerschmidt, F. NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl) piperidine enantiomers and of related compounds. Bioorg Med Chem 2009;17:34563462.Google Scholar
Wallach, J, De Paoli, G, Adejare, A, Brandt, SD. Preparation and analytical characterization of 1-(1-phenylcyclohexyl)piperidine (PCP) and 1-(1-phenylcyclohexyl)pyrrolidine (PCPy) analogues. Drug Test Anal 2014;6:633650.Google Scholar
Anis, NA, Berry, SC, Burton, NR, Lodge, D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol 1983;79:565575.Google Scholar
Helander, A, Beck, O, Bäckberg, M. Intoxications by the dissociative new psychoactive substances diphenidine and methoxphenidine. Clin Toxicol (Phila) 2015;53:446453.Google Scholar
Morris, H, Wallach, J. From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. Drug Test Anal 2014;6:614632.Google Scholar
Domino, EF, Chodoff, P, Corssen, G. Pharmacologic effects of Ci-581, a new dissociative anesthetic, in man. Clin Pharmacol Ther 1965;6:279291.Google Scholar
Kalsi, SS, Wood, DM, Dargan, PI. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use. Emerg Health Threats J 2011;4:7107. https://doi.org/10.3402/ehtj.v4i0.7107Google Scholar
Quibell, R, Prummer, EC, Mihalyo, M, Twycross, R, Wilcock, A. Ketamine. J Pain Symptom Mgt 2011;41:640649.Google Scholar
Rabiner, EA. Imaging of striatal dopamine release elicited with NMDA antagonists: is there anything there to be seen? J Psychopharmacol 2007;21:253258.Google Scholar
Yanagihara, Y, Kariya, S, Ohtani, M, et al. Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes. Drug Metab Dispos 2001;29:887890.Google Scholar
World Health Organization. Model List of Essential Medicines: 19th List (April 2015) amended November 2015.Google Scholar
Liao, Y, Tang Y-L, Hao W. Ketamine and international regulations. Am J Drug Alcohol Abuse 2017(online). https://doi.org/10.1080/00952990.2016.1278449Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Ketamine: A Review of Use and Harm. London, Home Office, 2013.Google Scholar
Weil, A, Rosen, W. Chocolate to Morphine: Understanding Mind-Active Drugs. Boston, MA, Houghton Mifflin, 1983.Google Scholar
Corazza, O, Schifano, F, Simonato, P, et al. Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine. Hum Psychopharmacol 2012;27(2):145149. https://doi.org/10.1002/hup.1242Google Scholar
Copeland, J, Dillon, P. The health and psycho-social consequences of ketamine use. Int J Drug Policy 2005;16:122131.Google Scholar
Hijazi, Y, Boulieu, R. Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes. Drug Metab Dispos 2002;30:853858.Google Scholar
Halberstadt AL, , Slepak N, , Hyun J, , Buell MR, , Powell SB. The novel ketamine analog methoxetamine produces dissociative-like behavioral effects in rodents. Psychopharmacology 2016;233:12151225. https://doi.org/10.1007/s00213-016-4203-3Google Scholar
Gibbons, S, Zloh, M. An analysis of the ‘legal high’ mephedrone. Bioorg Med Chem Lett 2010;20:41354139.Google Scholar
Hofer, KE, Grager, B, Müller, DM, et al. Ketamine-like effects after recreational use of methoxetamine. Ann Emerg Med 2012;60(1):9799. https://doi.org/10.1016/j.annemergmed.2011.11.018Google Scholar
Roth, BL, Gibbons, S, Arunotayanun, W, et al. The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. PLoS One 2013;8(3):e59334. https://doi.org/10.1371/ journal.pone.0059334Google Scholar
Zanda, MT, Fadda, P, Antinori, S, et al. Methoxetamine affects brain processing involved in emotional response in rats. Br J Pharmacol 2017;174(19):33333345. https://doi.org/10.1111/bph.13952Google Scholar
Coppola, M, Mondola, R. Methoxetamine: from drug of abuse to rapid-acting antidepressant. Med Hypotheses 2012;79:504507.Google Scholar
Corazza, O, Assi, S, Schifano, F. From ‘Special K’ to ‘Special M’: the evolution of the recreational use of ketamine and methoxetamine. CNS Neurosci Ther 2013;19:454460.Google Scholar
Corazza, O, Schifano, F, Simonato, P, et al. Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine. Hum Psychopharmacol Clin Exp 2012;27:145149.Google Scholar
Winstock AR, , Lawn W, , Deluca P, , Borschmann R., Methoxetamine: an early report on the motivations for use, effect profile and prevalence of use in a UK clubbing sample. Drug Alcohol Rev 2016;35:212217. https://doi.org/10.1111/dar.12259Google Scholar
Lawn, W, Borschmann, R, Cottrell, A, Winstock, A. Methoxetamine: prevalence of use in the USA and UK and associated urinary problems. J Subst Use 2016;21:115120.Google Scholar
Dargan, P, Tang, H, Liang, W, Wood, D, Yew, D. Three months of methoxetamine administration is associated with significant bladder and renal toxicity in mice. Clin Toxicol 2014;52:176180.Google Scholar
Wang, Q, Wu, Q, Wang, J, et al. Ketamine analog methoxetamine induced inflammation and dysfunction of bladder in rats. Int J Mol Sci 2017;18:117.Google Scholar
Botanasa CJ, , Bryan de la, Penaa J, , Kima HJ, , Sup Lee Y, , Hoon J., Methoxetamine: a foe or friend? Neurochem Int 2019; 122:17.Google Scholar
Karlow, N, Schlaepfer, C H, Stoll, C RT, et al. A systematic review and meta-analysis of ketamine as an alternative to opioids for acute pain in the emergency department. Acad Emerg Med 2018;25(10):10861097. https://doi.org/10.1111/acem.13502Google Scholar
National Poisons Information Service. Annual Report 2012/2013. London, Public Health England, 2013.Google Scholar
Jones, JL, Mateus, CF, Malcolm, RJ, Brady, KT, Back, SE. Efficacy of ketamine in the treatment of substance use disorders: a systematic review. Front Psychiatry 2018;9:277. https://doi.org/10.3389/fpsyt.2018.00277Google Scholar
Malhi GS, , Byrow Y, , Cassidy F, et al. Ketamine: stimulating antidepressant treatment? BJPsych Open 2016;2:e5e9. https://doi.org/10.1192/bjpo.bp.116.002923Google Scholar
Singh I, , Morgan C, , Curran V., Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight. Lancet Psychiatry 2017;4(5):419426.Google Scholar
Schoevers RA, , Chaves TV, , Balukova SM, , van het Rot M, Kortekaas R. Oral ketamine for the treatment of pain and treatment-resistant depression Br J Psychiatry 2016;208:108113. https://doi.org/1192/bjp.bp.115.165498Google Scholar
Swiatek KM, Jordan K, Coffman J. New use for an old drug: oral ketamine for treatment-resistant depression. Br Med J Case Rep 2016 (online). https://doi.org/10.1136/bcr-2016-216088Google Scholar
Zarate, CA, Singh, JB, Carlson, PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63(8):856864.Google Scholar
Krystal, JH. Ketamine and the potential role for rapid acting antidepressant medications. Swiss Med Wkly 2007;137:215216.Google Scholar
Schwartz J, , Murrough JW, , Iosifescu DV. Ketamine for treatment-resistant depression: recent developments and clinical applications Evid Based Mental Health 2016;19(2):3538.Google Scholar
Mathew, SJ, Shah, A, Lapidus, K, et al. Ketamine for treatment-resistant unipolar depression. CNS Drugs 2012;26:189204.Google Scholar
Murrough, JW, Iosifescu, DV, Chang, LC, et al. An antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry 2013;170:11341142.Google Scholar
Fond, G, Loundou, A, Rabu, C, et al. Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology (Berl) 2014;231:36633676.Google Scholar
McGirr, A, Berlim, MT, Bond, DJ, et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med 2015;45:693704.Google Scholar
SchakJennifer KM, Van de Voort L, , Johnson EK, et al. Potential risks of poorly monitored ketamine use in depression treatment. Am J Psychiatry 2016;173:3.Google Scholar
DeWilde, KE, Levitch, CF, Murrough, JW, Mathew, SJ, Iosifescu, DV. The promise of ketamine for treatment-resistant depression: current evidence and future directions. Ann N Y Acad Sci 2015;1345;4758. https://doi.org/10.1111/nyas.12646Google Scholar
Short B, , Fong J, , Galvez V, , Shelker W, , Loo CK. Side-effects associated with ketamine use in depression: a systematic review. Lancet Psychiatry 2018;5:6578. https://doi.org/10.1016/ S2215-0366(17)30272-9Google Scholar
Berman, RM, Cappiello, A, Anand, A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000;47(4):351354.Google Scholar
Zarate, CA, Singh, JB, Carlson, PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63(8):856864.Google Scholar
Krystal, JH. Ketamine and the potential role for rapid acting antidepressant medications. Swiss Med Wkly 2007;137:215216.Google Scholar
Bell RF. Ketamine for chronic noncancer pain: concerns regarding toxicity. Curr Opin Support Palliat Care 2012;6(2):183187. https://doi.org/10.1097/SPC.0b013e328352812cGoogle Scholar
Zhu W, , Ding Z, , Zhang Y, , Shi J, , Hashimoto K, , Lu L. Risks associated with misuse of ketamine as a rapid-acting antidepressant. Neurosci Bull 2016;32(6):557564. https://doi.org/10.1007/s12264-016-0081-2Google Scholar
Botanasa CJ, , Bryan de la, Penaa J, , Kima HJ, , Lee YS, , Cheonga JH., Methoxetamine: a foe or friend? Neurochem Int 2019;122:17.Google Scholar
Coppola, M, Mondola, R. Methoxetamine: from drug of abuse to rapid-acting antidepressant. Med Hypotheses 2012;79:504507.Google Scholar
Botanas, CJ, de la Pena, JB, Custodio, RJ, de la PenKim, HI, Cho, MC, Lee, YS. Methoxetamine produces rapid and sustained antidepressant effects probably via glutamatergic and serotonergic mechanisms. Neuropharmacology 2017;126:121127.Google Scholar
Zanda, M, Fadda, P, Antinori, S, et al. Methoxetamine affects brain processing involved in emotional response in rats. Br J Pharmacol 2017;174:33333345.Google Scholar
Sayson, L V, Botanas, C J, Custodio, RJ et al. The novel methoxetamine analogs N-ethylnorketamine hydrochloride (NENK), 2-MeO-N-ethylketamine hydrochloride (2-MeO-NEK), and 4-MeO-N-ethylketamine hydrochloride (4-MeO-NEK) elicit rapid antidepressant effects via activation of AMPA and 5-HT2 receptors. Psychopharmacology 2019;236(7):22012210. https://doi.org/10.1007/s00213-019-05219-xGoogle Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). 2012 Annual Report on the State of the Drug Problem in Europe.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). European Drug Report 2019: Trends and Developments. Luxembourg, Publications Office of the European Union, 2019.Google Scholar
Moore, K, Measham, F.It’s the most fun you can have for twenty quid’: motivations, consequences and meanings of British ketamine use. Addict Res Theory 2008;16(3):231244.Google Scholar
Curran, V, Morgan, C. Cognitive, dissociative and psychotogenic effects of ketamine in recreational users on the night of drug use and 3 days later. Addiction 2000;95:575590.Google Scholar
Dillon, P, Copeland, J, Jansen, K. Patterns of use and harms associated with non-medical ketamine use. Drug Alcohol Depend 2003;69:2328.Google Scholar
Clatts, MC, Goldsamt, L, Huso, Y. Club drug use among young men who have sex with men in NYC: a preliminary epidemiological profile. Subst Use Misuse 2005;40:13171330.Google Scholar
Dalgarno, PJ, Shewan, D. Illicit use of ketamine in Scotland. J Psychoactive Drugs 1996;28:191199.Google Scholar
Long, H. Case report: ketamine medication error resulting in death. Int J Med Toxicol 2003;6:2.Google Scholar
Licata, M, Pierini, G, Popoli, G. A fatal ketamine poisoning. J Forensic Sci 1994;39:13141320.Google Scholar
World Drug Report 2019 (United Nations publication, Sales No. E.19.XI.8).Google Scholar
Riley, SC, James, C, Gregory, D, Dingle, H, Cadger, M. Patterns of recreational drug use at dance events in Edinburgh, Scotland. Addiction 2001;96(7):10351047.Google Scholar
Mitcheson, L, McCambridge, J, Byrne, A, Hunt, N, Winstock, A. Sexual health risk among dance drug users: cross-sectional comparisons with nationally representative data. Int J Drug Policy 2008;19(4):304310. https://doi.org/10.1016/j.drugpo.2007.02.002Google Scholar
Darrow, WW, Biersteker, S, Geiss, T, et al. Risky sexual behaviors associated with recreational drug use among men who have sex with men in an international resort area: challenges and opportunities. J Urban Health 2005;82:601609.Google Scholar
Lee, SJ, Galanter, M, Dermatis, H, McDowell, D. Circuit parties and patterns of drug use in a subset of gay men. J Addictive Diseases 2003;22(4):4760.Google Scholar
Mattison, AM, Ross, MW, Wolfson, T, Franklin, D. Circuit party attendance, club drug use, and unsafe sex in gay men. J Subst Abuse 2001;13(1–2):119126.Google Scholar
Ross, MW, Mattison, AM, Franklin, D. Club drugs and sex on drugs are associated with different motivations for gay circuit party attendance in men. Subst Use Misuse 2003;38(8):11711179.Google Scholar
Jang, MY, Long CY, , Chuang SM, et al. Sexual dysfunction in women with ketamine cystitis: a case-control study. BJU Int 2012;110(3):427431. https://doi.org/10.1111/j.1464-410X.2011.10780.xGoogle Scholar
Suppiah, B, Vicknasingam B, , Singh D, , Narayanan S, . Erectile dysfunction among people who use ketamine and poly-drugs. J Psychoactive Drugs 2016;48(2):8692.Google Scholar
Lankenau, SE, Bloom, JJ, Shin, C. Longitudinal trajectories of ketamine use among young injection drug users. Int J Drug Policy 2010;21(4):306314. https://doi.org/10.1016/j.drugpo.2010.01.007Google Scholar
Lankenau, SE, Clatts, MC. Ketamine injection among high-risk youths: preliminary findings from New York City. J Drug Issues 2002;32(3):893905.Google Scholar
Bristol Drug Project. Ketamine: just a harmless party drug? Drink and Drug News, 28 July 2008.Google Scholar
Darke S, , Duflou J, , Farrell M, , Peacock, A, Lappin, J. Characteristics and circumstances of death related to the self‐administration of ketamine. Addiction 2020 (online). https://doi.org/10.1111/add.15154Google Scholar
Han E, , Kwon NJ, , Feng L-Y, , Li J-H, , Chung, H. Illegal use patterns, side effects, and analytical methods of ketamine. Forensic Sci Int 2016;268:2534. https://doi.org/10.1016/j.forsciint.2016.09.001Google Scholar
Sinner, B, Graf, BM. Ketamine. Handb Exp Pharmacol 2008;182:313333.Google Scholar
Jansen, KL. A review of the nonmedical use of ketamine: use, users and consequences. J Psychoactive Drugs 2000;32:419433.Google Scholar
Corazza, O, Assi, S, From, Schifano F.Special K’ to ‘Special M’: the evolution of the recreational use of ketamine and methoxetamine. CNS Neurosci Ther 2013;19(6):454460. https://doi.org/10.1111/cns.12063Google Scholar
Curran, HV, Monaghan, L. In and out of the K-hole: a comparison of the acute and residual effects of ketamine in frequent and infrequent ketamine users. Addiction 2001;96(5):749760.Google Scholar
Jansen, KL, Darracot-Cankovic, R. The nonmedical use of ketamine, part two: a review of problem use and dependence. J Psychoactive Drugs 2001;33:151158.Google Scholar
Morgan, CJ, Rees, H, Curran, HV. Attentional bias to incentive stimuli in frequent ketamine users. Psychol Med 2008;38:13311340.Google Scholar
Moreton, JE, Meisch, RA, Stark, L, Thompson, T. Ketamine self-administration by the rhesus monkey. J Pharmacol Exp Ther 1977;203:303309.Google Scholar
Wood, D, Cottrell, A, Baker, SC, et al. Recreational ketamine: from pleasure to pain. BJU Int 2011;107(12):18811884. https://doi.org/10.1111/j.1464-410X.2010.10031.xGoogle Scholar
Rosenbaum, CD, Carreiro, SP, Babu, KM. Here today, gone tomorrow … and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (Bath Salts), Kratom, Salvia divinorum, methoxetamine, and piperazines. J Med Toxicol 2012;8(1):1532. https://doi.org/10.1007/ s13181-011-0202-2Google Scholar
Corazza, O, Schifano, F, Simonato, P, et al. The phenomenon of new drugs on the Internet: a study on the diffusion of the ketamine derivative methoxetamine (‘MXE’). Hum Psychopharmacol 2012;27:145149.Google Scholar
Corazza, O, Assi, S, Schifano, F. From ‘Special K’ to ‘Special M’: the evolution of the recreational use of ketamine and methoxetamine. CNS Neurosci Ther 2013;19:454e460. https://doi.org/10.1111/cns.12063Google Scholar
Hondebrink L, , Kasteel EEJ, , Tukker AM, et al. Neuropharmacological characterization of the new psychoactive substance methoxetamine. Neuropharmacology 2017;123:19.Google Scholar
Winstock AR, , Lawn W, , Deluca P, , Borschmann, R. Methoxetamine: an early report on the motivations for use, effect profile and prevalence of use in a UK clubbing sample. Drug Alcohol Rev 2016;35:212217. https://doi.org/10.1111/dar.12259Google Scholar
Craig CL, , Loeffler GH., The ketamine analog methoxetamine: a new designer drug to threaten military readiness. Mil Med 2014;179(10): 1149.Google Scholar
Botanasa CJ, Bryan de la Pena, J, Kima HJ, , Lee YS, , Cheonga JH. Methoxetamine: a foe or friend? Neurochem Int 2019; 122:17.Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Statement of Evidence on Methoxetamine. London, Home Office, 2012.Google Scholar
Gerace, E, Bovetto, E, Di Corcia, D, Vincenti, M, Salomone, A. A case of nonfatal intoxication associated with the recreational use of diphenidine. J Forensic Sci 2017;62:11071111.Google Scholar
Siegel, RK. Phencyclidine and ketamine intoxication: a study of four populations of recreational users. In: Peterson, RC, Stillman, RC, eds. Phencyclidine Abuse: An Appraisal (NIDA Research Monograph 21), pp. 119147. Bethesda, MD, National Institute on Drug Abuse, 1978.Google Scholar
Benschop, A, Urbán, R, Kapitány-Fövény, M, et al. Why do people use new psychoactive substances? Development of a new measurement tool in six European countries. J Psychopharmacol 2020;34(6):600611. https://doi.org/10.1177/0269881120904951Google Scholar
Teltzrow, R, Bosch, OG. Ecstatic anaesthesia: ketamine and GHB between medical use and self-experimentation. Appl Cardiopulm Pathophysiol 2012;16:309321.Google Scholar
Hurt, PH, Ritchie, EC. A case of ketamine dependence. Am J Psychiatry 1994;151:779.Google Scholar
Teltzrow, R, Bosch, OG. Ecstatic anaesthesia: ketamine and GHB between medical use and self-experimentation. Appl Cardiopulm Pathophysiol 2012;16:309321.Google Scholar
Ross, S. Ketamine and addiction. Prim Psychiatry 2008;15(9):6169.Google Scholar
Wolff K. Ketamine: the pharmacokinetics and pharmacodynamics in misusing populations. In: The SAGE Handbook of Drug & Alcohol Studies. London: Sage Publications, 2016.Google Scholar
Stirling, J, McCoy, L. Quantifying the psychological effects of ketamine: from euphoria to the K-hole. Subst Use Misuse. 2010;45(14):24282443. https://doi.org/10.3109/10826081003793912Google Scholar
Leary, T, Sirius, RU. Design for Dying. London: HarperCollins, 1998.Google Scholar
Critchlow, DG. A case of ketamine dependence with discontinuation symptoms. Addiction 2006;101(8):12121213.Google Scholar
Gill, JR, Stajíc, M. Ketamine in non-hospital and hospital deaths in New York City. J Forensic Sci 2000;45(3):655658.Google Scholar
Corazza, O, Schifano, F. Ketamine-induced near-death experience states in a sample of 50 misusers. Subst Use Misuse 2010;45(6):916924.Google Scholar
Corazza, O, Assi, S, Schifano, F. From ‘Special K’ to ‘Special M’: the evolution of the recreational use of ketamine and methoxetamine. CNS Neurosci Ther 2013;19:454e460. https://doi.org/10.1111/cns.12063Google Scholar
Corazza, O, Schifano, F, Simonato, P, et al. Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine. Hum Psychopharmacol 2012;27:145e149. https://doi.org/10.1002/hup.1242Google Scholar
Horsley, RR, Lhotkova, E, Hajkova, K, Jurasek, B, Kuchar, M, Palenicek, T. Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue: behavioural, pharmacokinetic and metabolic studies in the Wistar rat. Brain Res Bull 2016 (online). https://doi.org/10.1016/j.brainresbull.2016.05.002Google Scholar
Van, Hout MC, Hearne, E.Word of Mouse’: indigenous harm reduction and online consumerism of the synthetic compound methoxphenidine. J Psychoactive Drugs 2015;47(1):3041https://doi.org/10.1080/02791072.2014.974002Google Scholar
Botanasa CJ, Bryan de la Pena, J, Kima HJ, Lee YS, Cheonga JH., Methoxetamine: a foe or friend? Neurochem Int 2019;122:17.Google Scholar
Zawilska, JB. Methoxetamine: a novel recreational drug with potent hallucinogenic properties. Toxicol Lett 2014;230:402e407. https://doi.org/ 10.1016/j.toxlet.2014.08.011Google Scholar
Corazza, O, Assi, S, Schifano, F. From ‘Special K’ to ‘Special M’: the evolution of the recreational use of ketamine and methoxetamine. CNS Neurosci Ther 2013;19:454e460. https://doi.org/10.1111/cns.12063Google Scholar
Corazza, O, Schifano, F, Simonato, P, et al. Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine. Hum Psychopharmacol 2012;27:145e149. https://doi.org/10.1002/hup.1242Google Scholar
Hout MC, Van, Hearne E., Word of Mouse’: indigenous harm reduction and online consumerism of the synthetic compound methoxphenidine. J Psychoactive Drugs 2015;47(1):3041https://doi.org/10.1080/02791072.2014.974002Google Scholar
Schifano, F, Corkery, J, Oyefeso, A, Tonia, T, Ghodse, AH. Trapped in the ‘K-hole’: overview of deaths associated with ketamine misuse in the UK (1993–2006). J Clin Psychopharmacol 2008;28:114116.Google Scholar
Corazza, O, Assi, S, Schifano, F. From ‘Special K’ to ‘Special M’: the evolution of the recreational use of ketamine and methoxetamine. CNS Neurosci Ther 2013;19:454e460. https://doi.org/10.1111/cns.12063Google Scholar
Craig, CL, Loeffler, GH. The ketamine analog methoxetamine: a new designer drug to threaten military readiness. Mil Med 2014;179:11491157.Google Scholar
Zanda, MT, Fadda, P, Chiamulera, C, Fratta, W, Fattore, L. Methoxetamine: a novel psychoactive substance with serious adverse pharmacological effects: a review of case reports and preclinical findings. Behav Pharmacol 2016;27:489496.Google Scholar
Morgan, CJA, Curran, HV. Ketamine use: a review. Addiction 2011;107:2738.Google Scholar
Morgan, CJ, Curran, HV. Acute and chronic effects of ketamine upon human memory: a review. Psychopharmacology (Berl) 2006;188:408424.Google Scholar
Haas, DA, Harper, DG. Ketamine: a review of its pharmacological properties and use in ambulatory anesthesia. Anesth Prog 1992:39:6168.Google Scholar
Weiner, AL, Vieira, L, McKay, CA, Bayer, MJ. Ketamine abusers presenting to the emergency department: a case series. J Emerg Med 2000;18:447451.Google Scholar
Sassano-Higgins S, , Baron D, Juarez G, , Esmaili N, , Gold M. A review of ketamine abuse and diversion. Depress Anxiety 2016;33:718727.Google Scholar
SPC data for ketamine hydrochloride for injection. SPC states that respiratory depression may occur with overdosage.Google Scholar
Ng, SH, Tse, ML, Ng, HW, Lau, FL. Emergency department presentation of ketamine abusers in Hong Kong: a review of 233 cases. Hong Kong Med J 2010;16(1):611.Google Scholar
Felser, JM, Orban, DJ. Dystonic reaction after ketamine abuse. Ann Emerg Med 1982;11(12):673675.Google Scholar
Lahti, AC, Weiler, MA, Michaelidis, T, Parwani, A, Tammminga, C. Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology 2001;25:455467.Google Scholar
Lahti, AC, Koffel, B, LaPorte, D, Tamminga, CA. Subanesthetic doses of ketamine stimulate psychosis in schizophrenia. Neuropsychopharmacology 1995;13:919.Google Scholar
Malhotra, AK, Pinals, DA, Adler, CM, et al. Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Neuropsychopharmacology 1997;17:141150.Google Scholar
Lahti, AC, Holcomb, HH, Medoff, DR, Tamminga, CA. Ketamine activates psychosis and alters limbic blood flow in schizophrenia. Neuroreport 1995;6:869872.Google Scholar
Wood, DM, Bishop, CR, Greene, SL, Dargan, PI. Ketamine-related toxicology presentations to the ED. Clin Toxicol 2008;46:630.Google Scholar
Weiner, AL, Vieira, L, McKay, CA, Bayer, MJ. Ketamine abusers presenting to the emergency department: a case series. J Emerg Med 2000;18:447451.Google Scholar
Rollin, A, Maury, P, Guilbeau-Frugier, C, Transient, Brugada J. ST elevation after ketamine intoxication: a new cause of acquired brugada ECG pattern. J Cardiovasc Electrophysiol 2011;22(1):9194. https://doi.org/10.1111/j.1540-8167.2010.01766.xGoogle Scholar
Maskell SF, Bailey ML, Rutherfoord Rose S., Self-medication with methoxetamine as an analgesic resulting in significant toxicity. Pain Med 2016;17:1773–1775. https://doi.org/10.1093/pm/pnw041Google Scholar
Craig CL, , Loeffler GH., The ketamine analog methoxetamine: a new designer drug to threaten military readiness. Mil Med 2014;179(10): 1149.Google Scholar
Shields, JE, Dargan, PI, Wood, DM, Puchnarewicz, M, Davies, S, Waring, WS. Methoxetamine associated reversible cerebellar toxicity: three cases with analytical confirmation. Clin Toxicol (Phila) 2012;50(5):438440. https://doi.org/10.3109/15563650.2012.683437Google Scholar
Michelot, D, Melendez-Howell, LM. Amanita muscaria: chemistry, biology, toxicology, and ethnomycology. Mycol Res 2003;107:131146.Google Scholar
Wood, DM, Davies, S, Puchnarewicz, M, Johnston, A, Dargan, PI. Acute toxicity associated with the recreational use of the ketamine derivative methoxetamine. Eur J Clin Pharmacol 2012;68(5):853856. https://doi.org/10.1007/s00228-011-1199-9Google Scholar
Ward, J, Rhyee, S, Plansky, J, Boyer, E. Methoxetamine: a novel ketamine analog and growing health-care concern. Clin Toxicol 2011;49:874875.Google Scholar
Craig CL, , Loeffler GH., The ketamine analog methoxetamine: a new designer drug to threaten military readiness. Mil Med 2014;179(10):1149.Google Scholar
Shields, JE, Dargan, PI, Wood, DM, Puchnarewicz, M, Davies, S, Waring, WS. Methoxetamine-associated reversible cerebellar toxicity: three cases with analytical confirmation. Clin Toxicol 2012;50:438440.Google Scholar
Wood, DM, Davies, S, Puchnarewicz, M, Johnston, A, Dargan, PI. Acute toxicity associated with the recreational use of the ketamine derivative methoxetamine. Eur J Clin Pharmacol 2012;68:853856. https://doi.org/10.1007/s00228-011-1199-9Google Scholar
Sein Anand, J, Wiergowski, M, Barwina, M, Kaletha, K. Accidental intoxication with high dose of methoxetamine (MXE) – a case report. Przegl Lek 2012;69(8):609610.Google Scholar
Corazza, O, Assi, S, Schifano, F. From ‘Special K’ to ‘Special M’: the evolution of the recreational use of ketamine and methoxetamine. CNS Neurosci Ther 2013;19:454e460. http://dx.doi.org/10.1111/cns.12063Google Scholar
Zawilska, JB. Methoxetamine: a novel recreational drug with potent hallucinogenic properties. Toxicol Lett 2014;230:402e407. https://doi.org/ 10.1016/j.toxlet.2014.08.011Google Scholar
Shields, JE, Dargan, PI, Wood, DM, Puchnarewicz, M, Davies, S, Waring, WS. Methoxetamine-associated reversible cerebellar toxicity: three cases with analytical confirmation. Clin Toxicol 2012;50:438440.Google Scholar
Bäckberg M, , Beck O, , Helander A., Phencyclidine analog use in Sweden: intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project. Clin Toxicol 2015;53(9):856864. https://doi.org/10.3109/15563650.2015.1079325Google Scholar
Bakota E, , Arndt C, , Romoser AA, Wilson SK. Fatal intoxication involving 3-MeO-PCP: a case report and validated method. J Anal Toxicol 2016;40:504510. https://doi.org/10.1093/jat/bkw056Google Scholar
Jacobs, R, Nowell, M. Phencyclidine hydrochloride: a challenge to medicine. J Natl Med Assoc 1981;73:170172.Google Scholar
Bey, T, Patel, A. Phencyclidine intoxication and adverse effects: a clinical and pharmacological review of an illicit drug. Calif J Emerg Med 2007;8:914.Google Scholar
Johansson A, , Lindsted D, , Roman M, et al. A non-fatal intoxication and seven deaths involving the dissociative drug 3-MeO-PCP. Forensic Sci Int 2017;275:7682.Google Scholar
Bakota E, , Arndt C, , Romoser AA, , Wilson SK., Fatal intoxication involving 3-MeO-PCP: a case report and validated method. J Anal Toxicol 2016;40:504510. https://doi.org/10.1093/jat/bkw056Google Scholar
Jacobs, R, Nowell, M. Phencyclidine hydrochloride: a challenge to medicine. J Natl Med Assoc 1981;73:170172.Google Scholar
Bey, T, Patel, A. Phencyclidine intoxication and adverse effects: a clinical and pharmacological review of an illicit drug. Calif J Emerg Med 2007;8:914.Google Scholar
Bakota E, , Arndt C, , Romoser AA, , Wilson SK., Fatal intoxication involving 3-MeO-PCP: a case report and validated method. J Anal Toxicol 2016;40:504510. https://doi.org/10.1093/jat/bkw056Google Scholar
Jacobs, R, Nowell, M. Phencyclidine hydrochloride: a challenge to medicine. J Natl Med Assoc 1981;73:170172.Google Scholar
Bey, T, Patel, A. Phencyclidine intoxication and adverse effects: a clinical and pharmacological review of an illicit drug. Calif J Emerg Med 2007;8:914.Google Scholar
Bäckberg M, , Beck O, , Helander A., Phencyclidine analog use in Sweden: intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project. Clin Toxicol 2015;53(9):856864. https://doi.org/10.3109/15563650.2015.1079325Google Scholar
Thornton, S, Lisbon, D, Lin, T, Gerona, R. ketamine, Beyond and phencyclidine: analytically confirmed use of multiple novel arylcyclohexylamines. J Psychoactive Drugs 2017;49(4):289293. https://doi.org/10.1080/02791072.2017.1333660Google Scholar
Thornton, S, Lisbon, D, Lin, T, Gerona, R. Beyond ketamine and phencyclidine: analytically confirmed use of multiple novel arylcyclohexylamines. J Psychoactive Drugs 2017;49(4);289293. https://doi.org/10.1080/02791072.2017.1333660Google Scholar
Bertol E, , Pascali J, , Palumbo D, et al. 3-MeO-PCP intoxication in two young men: first in vivo detection in Italy. Forensic Sci Int 2017;274:712.Google Scholar
Orsolin L, , Papanti G, , Schifano, FR. Methoxphenidine (1-(1-(2-methoxyphenyl)-2-phenylethyl) Piperidine; 2-meo-diphenidine): preliminary data on chemical, pharmacological and clinical effects. Eur Psychiatry 2015;30(Suppl.1):1046.Google Scholar
Helander A, , Beck O, , Bäckberg M., Intoxications by the dissociative new psychoactive substances diphenidine and methoxphenidine. Clin Toxicol 2015;53(5):446453https://doi.org/10.3109/15563650.2015.1033630Google Scholar
Hofer KE, , Degrandi C, , Müller DM, et al. Acute toxicity associated with the recreational use of the novel dissociative psychoactive substance methoxphenidine. Clin Toxicol 2014;52(10):12881291. https://doi.org/10.3109/15563650.2014.974264Google Scholar
Hofer KE, , Degrandi C, , Müller DM, et al. Acute toxicity associated with the recreational use of the novel dissociative psychoactive substance methoxphenidine. Clin Toxicol 2014;52(10):12881291. https://doi.org/10.3109/15563650.2014.974264Google Scholar
Helander A, , Beck O, , Bäckberg M., Intoxications by the dissociative new psychoactive substances diphenidine and methoxphenidine. Clin Toxicol 2015;53(5):446453https://doi.org/10.3109/15563650.2015.1033630Google Scholar
Hofer KE, , Degrandi C, , Müller DM, et al. Acute toxicity associated with the recreational use of the novel dissociative psychoactive substance methoxphenidine. Clin Toxicol 2014;52(10):12881291. https://doi.org/10.3109/15563650.2014.974264Google Scholar
Helander, A, Beck, O, Bäckberg, M. Intoxications by the dissociative new psychoactive substances diphenidine and methoxphenidine. Clin Toxicol 2015;53:446453.Google Scholar
Hofer, EK, Degrandi, C, Müller, DM, et al. Acute toxicity associated with the recreational use of the novel dissociative psychoactive substance methoxphenidine. Clin Toxicol 2014;52:12881291.Google Scholar
Gerace, E, Bovetto, E, Di Corcia, D, Vincenti, M, Salomone, A. A case of nonfatal intoxication associated with the recreational use of diphenidine. J Forensic Sci 2017;62:11071111.Google Scholar
Hofer, EK, Degrandi, C, Müller, DM, et al. Acute toxicity associated with the recreational use of the novel dissociative psychoactive substance methoxphenidine. Clin Toxicol 2014;52:12881291.Google Scholar
Lam RPK, , Yip WL, , Tsui MSH, , Ng SW, , Ching CK, , Mak TWL., Severe rhabdomyolysis and acute kidney injury associated with methoxphenidine. Clin Toxicol 2016;54(5):464465https://doi.org/10.3109/15563650.2016.1157724Google Scholar
Orsolin L, , Papanti G, , Schifano, FR. Methoxphenidine (1-(1-(2-methoxyphenyl)-2-phenylethyl) Piperidine; 2-meo-diphenidine): preliminary data on chemical, pharmacological and clinical effects. Eur Psychiatry 2015;30(Suppl. 1):1046.Google Scholar
Tang MHY, , Chong YK, , Chan CY, , et al. Cluster of acute poisonings associated with an emerging ketamine analogue, 2-oxo-PCE. Forensic Sci Int 2018;290:238243.Google Scholar
Tang MHY, , Chong YK, , Chan CY, , et al. Cluster of acute poisonings associated with an emerging ketamine analogue, 2-oxo-PCE. Forensic Sci Int 2018;290:238243.Google Scholar
Dobbs, T. Report: after patient death, UVM medical center waited weeks to fix flawed systems. VPR, 7 July, 2015.Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Technical report on 2-(3-methoxyphenyl)- 2-(ethylamino)cyclohexanone (methoxetamine), Lisbon, EMCDDA, April 2014.Google Scholar
Darke S, , Duflou J, , Farrell M, , Peacock, A, Lappin J., Characteristics and circumstances of death related to the self‐administration of ketamine. Addiction 2020 (online). https://doi.org/10.1111/add.15154Google Scholar
Stewart, CE. Ketamine as a street drug. Emerg Med Serv 2001;30(11):30,32,34 passim.Google Scholar
Adamowicz P, , Zuba D. Fatal intoxication with methoxetamine. J Forensic Sci 2015;60(S1). https://doi.org/10.1111/1556-4029.12594Google Scholar
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Technical report on 2-(3-methoxyphenyl)- 2-(ethylamino)cyclohexanone (methoxetamine), Lisbon, EMCDDA, April 2014.Google Scholar
Elliott SP, , Brandt SD, , Wallach J, , Morris H, Kavanagh PV. First reported fatalities associated with the ‘research chemical’ 2-methoxydiphenidine. J Anal Toxicol 2015;39:287293. https://doi.org/10.1093/jat/bkv006Google Scholar
Adamowicz P, , Zuba D. Fatal intoxication with methoxetamine. J Forensic Sci 2015;60(S1). https://doi.org/10.1111/1556-4029.12594Google Scholar
Elliott SP, , Brandt SD, , Wallach J, , Morris H, Kavanagh PV. First reported fatalities associated with the ‘research chemical’ 2-methoxydiphenidine. J Anal Toxicol 2015;39:287293. https://doi.org/10.1093/jat/bkv006Google Scholar
Elliott S, , Sedefov R, , Evans‐Brown M. Assessing the toxicological significance of new psychoactive substances in fatalities. Drug Test Anal 2018;10:120.Google Scholar
Bäckberg M, , Beck O, , Helander A., Phencyclidine analog use in Sweden: intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project. Clin Toxicol 2015;53(9):856864. https://doi.org/10.3109/15563650.2015.1079325Google Scholar
Johansson A, , Lindsted D, , Roman M, et al. A non-fatal intoxication and seven deaths involving the dissociative drug 3-MeO-PCP. Forensic Sci Int 2017;275:7682.Google Scholar
Bäckberg M, , Beck O, , Helander A., Phencyclidine analog use in Sweden: intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project. Clin Toxicol 2015;53(9):856864. https://doi.org/10.3109/15563650.2015.1079325Google Scholar
Bakota E, , Arndt C, , Romoser AA, , Wilson SK., Fatal intoxication involving 3-MeO-PCP: a case report and validated method. J Anal Toxicol 2016;40:504510. https://doi.org/10.1093/jat/bkw056Google Scholar
McIntyre IM, , Trochta A, , Gary RD, , Storey A, , Corneal J, , Schaber B., Hallucinogenic compounds: 4-methoxyphencyclidine and 4-hydroxy-N-methyl-N-ethyltryptamine. J Anal Toxicol 2015;39(9):751755https://doi.org/10.1093/jat/bkv089Google Scholar
de Jong LAA, , Olyslager EJH, , Duijst WLJM., The risk of emerging new psychoactive substances: the first fatal 3-MeO-PCP intoxication in the Netherlands. J Forensic Leg Med 2019;65:101104.Google Scholar
Mitchell-Mata C, , Thomas B, , Peterson B, , Couper, F. Two fatal intoxications involving 3-methoxyphencyclidine. J Anal Toxicol 2017;41:503507. https://doi.org/10.1093/jat/bkx048Google Scholar
Zidkova M, , Hlozek T, , Balik M, et al. Two cases of non-fatal intoxication with a novel street hallucinogen: 3-methoxy-phencyclidine. J Anal Toxicol 2017;41:350354. https://doi.org/10.1093/jat/bkx009Google Scholar
Wood, DM, Nicolaou, M, Dargan, PI. Epidemiology of recreational drug toxicity in a nightclub environment. Subst Use Misuse 2009;44:14951502.Google Scholar
Tang MHY, , Chong YK, , Chan CY, , et al. Cluster of acute poisonings associated with an emerging ketamine analogue, 2-oxo-PCE. Forensic Sci Int 2018;290:238243.Google Scholar
Smith, KM, Larive, LL, Romanelli, F. Club drugs: methylene dioxymethamphetaine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate. Am J Health Syst Pharm 2002;59(11):10671076.Google Scholar
Shields JE, , Dargan PI, , Wood DM, , Waring WS., Methoxetamine-associated reversible cerebellar toxicity: three cases with analytical confirmation. Clin Toxicol 2012;50(5):438440. https://doi.org/10.3109/15563650.2012.683437Google Scholar
Craig CL, , Loeffler GH, . The ketamine analog methoxetamine: a new designer drug to threaten military readiness. Mil Med 2014;179(10): 1149.Google Scholar
Craig CL, , Loeffler GH, . The ketamine analog methoxetamine: a new designer drug to threaten military readiness. Mil Med 2014;179(10): 1149.Google Scholar
Wood, DM, Dargan PI. Novel psychoactive substances: how to understand the acute toxicity associated with the use of these substances. Ther Drug Monit 2012;34(4):363366.Google Scholar
Wood DM, , Davies S, , Puchnarewicz M, , Johnston A, , Dargan PI. Acute toxicity associated with the recreational use of the ketamine derivative methoxetamine. Eur J Clin Pharmacol 2012;68:853856. https://doi.org/10.1007/s00228-011-1199-9Google Scholar
Shields JE, , Dargan PI, , Wood DM, , Waring WS., Methoxetamine-associated reversible cerebellar toxicity: three cases with analytical confirmation. Clin Toxicol 2012;50(5):438440. https://doi.org/10.3109/15563650.2012.683437Google Scholar
Bäckberg M, , Beck O, , Helander A., Phencyclidine analog use in Sweden: intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project. Clin Toxicol 2015;53(9):856864. https://doi.org/10.3109/15563650.2015.1079325Google Scholar
Tang MHY, , Chong YK, , Chan CY, , et al. Cluster of acute poisonings associated with an emerging ketamine analogue, 2-oxo-PCE. Forensic Sci Int 2018;290:238243.Google Scholar
Matulewicz, P, Kasicki, S, Hunt, MJ. The effect of dopamine receptor blockade in the rodent nucleus accumbens on local field potential oscillations and motor activity in response to ketamine. Brain Res 2010;1366:226232.Google Scholar
Moore, NN, Bostwick, JM. Ketamine dependence in anesthesia providers. Psychosomatics 1999;40:356359.Google Scholar
Pal, HR, Berry, N, Kumar, R, Ray, R. Ketamine dependence. Anaesth Intensive Care 2002;30:382384.Google Scholar
Jansen, KL. Ketamine – can chronic use impair memory? Int J Addict 1990;25:133139.Google Scholar
Cumming, JF. The development of an acute tolerance to ketamine. Anesth Analg 1976;55:788791.Google Scholar
Bree, MM, Feller, I, Corssen, G. Safety and tolerance of repeated anesthesia with CI 581 (ketamine) in monkeys. Anesth Analg 1967;46:596600.Google Scholar
Byer DE, , Gould, AB Jr. Development of tolerance to ketamine in an infant undergoing repeated anesthesia. Anesthesiology 1981;54:255256.Google Scholar
Muetzelfeldt, L, Kamboj, SK, Rees, H, Taylor, J, Morgan, CJ, Curran, HV. Journey through the K-hole: phenomenological aspects of ketamine use. Drug Alcohol Depend 2008;95(3):219229. https://doi.org/10.1016/j.drugalcdep.2008.01.024Google Scholar
Chen L-Y, , Chen C-K, , Chen C-H, , Chang H-M, , Huang M-C, , Xu K., Association of craving and depressive symptoms in ketamine‐dependent patients undergoing withdrawal treatment. Am J Addict 2020;29(1):4350https://doi.org/10.1111/ajad.12978Google Scholar
Striebel, JM, Nelson, EE, Kalapatapu, RK. ‘Being with a Buddha’: a case report of methoxetamine use in a United States veteran with PTSD. Case Rep Psychiatry 2017;7:2319094.Google Scholar
Botanasa CJ, , Bryan de la Pena J, Kima HJ, Lee YS, Hoon J. Methoxetamine: a foe or friend? Neurochem Int 2019;122:17.Google Scholar
Blachut, M, Solowiow, K, Janus, A, et al. A case of ketamine dependence. Psychiatr Pol 2009;43:593599.Google Scholar
Lim, DK. Ketamine-associated psychedelic effects and dependence. Singapore Med J 2003;44:3134.Google Scholar
Wang, YC, Chen, SK, Lin, CM. Breaking the drug addiction cycle is not easy in ketamine abusers. Int J Urol 2010;17(5):496. https://doi.org/10.1111/j.1442-2042.2010.02491.xGoogle Scholar
Monaghan, DT, Bridges, RJ, Cotman, CW. The excitatory amino acid receptors: their classes, pharmacology and distinct properties in the function of the central nervous system. Annu Rev Pharmacol Toxicol 1989;29:365402.Google Scholar
Craig CL, , Loeffler GH., The ketamine analog methoxetamine: a new designer drug to threaten military readiness. Mil Med 2014;179(10):1149.Google Scholar
Wei, YB, Yang, JR. ‘Ketamine-induced ulcerative cystitis’ is perhaps better labelled ‘ketamine-induced uropathy’. Addiction 2013;108(8):1515. https://doi.org/10.1111/add.12195Google Scholar
Chu, PS, Ma, WK, Wong, SC, et al. The destruction of the lower urinary tract by ketamine abuse: a new syndrome? BJU Int 2008;102(11):16161622. https://doi.org/10.1111/j.1464-410X.2008.07920.xGoogle Scholar
Wong, SW, Lee, KF, Wong, J, Ng, WW, Cheung, YS, Lai, PB. Dilated common bile ducts mimicking choledochal cysts in ketamine abusers. Hong Kong Med J 2009;15(1):5356.Google Scholar
Ramos SP, , Zambonato TK, , Graziott TM., Reduced functional bladder capacity associated with ketamine use. Braz J Psychiatry 2019;41(3):270271. https://doi.org/10.1590/1516-4446-2018-0314Google Scholar
Sihra N, , Ockrim J, , Wood D., The effects of recreational ketamine cystitis on urinary tract reconstruction – a surgical challenge. BJU Int 2018;121:458465.Google Scholar
Myers, FA, Bluth, MH, Cheung, WW Ketamine, : a cause of urinary tract dysfunction. Clin Lab Med 2016;36:721744.https://doi.org/10.1016/j.cll.2016.07.008Google Scholar
Gill P, , Logan K, , John B, , Reynolds F, , Shaw C, , Madden K. Participants’ experiences of ketamine bladder syndrome: a qualitative study. PhD Int J Urol Nurs 2018;12:7683.Google Scholar
Cottrell, A, Warren, K, Ayres, R, Weinstock, P, Gillatt, DA. The relationship of chronic recreational ketamine use and severe bladder pathology: presentation, management of symptoms and public health concerns. Eur Urol Suppl 2009;8:170.Google Scholar
Middela, S, Pearce, I. Ketamine-induced vesicopathy: a literature review. Int J Clin Pract 2011;65(1):2730. https://doi.org/10.1111/j.1742-1241.2010.02502.xGoogle Scholar
Gill P, , Logan K, , John B, , Reynolds F, , Shaw C, , Madden K. Participants’ experiences of ketamine bladder syndrome: a qualitative study. PhD Int J Urol Nurs 2018;12:7683.Google Scholar
Yew, DT, Wood, DM, Liang, W, Tang, HC, Dargan, PI. An animal model demonstrating significant bladder inflammation and fibrosis associated with chronic methoxetamine administration. Clin Toxicol 2013;51(4):278.Google Scholar
Lawn W, , Borschmann R, , Cottrell, A, Winstock A., Methoxetamine: prevalence of use in the USA and UK and associated urinary problems. J Subst Use 2016;21(2):115120. https://doi.org/10.3109/14659891.2014.966345Google Scholar
Liu, SUQ, Ng, SKK,Tam YH, et al. Clinical pattern and prevalence of upper gastrointestinal toxicity in patients abusing ketamine. J Dig Dis 2017;18(9):504510.Google Scholar
Liu, SUQ, Ng, SKK,Tam YH, et al. Clinical pattern and prevalence of upper gastrointestinal toxicity in patients abusing ketamine. J Dig Dis 2017;18(9):504510.Google Scholar
Liu, SUQ, Ng, SKK,Tam YH, et al. Clinical pattern and prevalence of upper gastrointestinal toxicity in patients abusing ketamine. J Dig Dis 2017;18(9):504510.Google Scholar
Selby, NM, Anderson, J, Bungay, P, Chesterton, LJ, Kohle, NV. Obstructive nephropathy and kidney injury associated with ketamine abuse. Nephrol Dial Transplant Plus 2008;1(2):310312.Google Scholar
Ng, SH, Lee, HK, Chan, YC, Lau, FL. Dilated common bile ducts in ketamine abusers. Hong Kong Med J 2009;15:157.Google Scholar
Wong, GL, Tam, YH, Ng, CF, et al. Liver injury is common among chronic abuses of ketamine. Clin Gastroenterol Hepatol 2014;12:17591762.Google Scholar
Wong, GL, Tam, YH, Ng, CF, et al. Liver injury is common among chronic abuses of ketamine. Clin Gastroenterol Hepatol 2014;12:17591762.Google Scholar
Yu, WL, Cho, CC, Lung, PF, et al. Ketamine-related cholangiopathy: a retrospective study on clinical and imaging findings. Abdom Imaging 2014;39:12411246.Google Scholar
Morgan, CJ, Curran, HV. Ketamine use: a review. Addiction 2011;107:2738.Google Scholar
Liu, SUQ, Ng, SKK,Tam YH, et al. Clinical pattern and prevalence of upper gastrointestinal toxicity in patients abusing ketamine. J Dig Dis 2017;18(9):504510.Google Scholar
Randall, T. Ectasy-fuelled ‘rave’ parties become dances of death for English youths. J Am Med Assoc 1993;269:869870.Google Scholar
Glasgow, AM, Tynan, D, Schwartz, R, et al. Alcohol and drug use in teenagers with diabetes mellitus. J Adolesc Health 1997;12:1114.Google Scholar
Gold, MA, Gladstein, J. Substance use among adolescents with diabetes mellitus: preliminary findings. J Adolesc Health 1993;14:8084.Google Scholar
Martínez-Aguayo, A, Araneda, JC, Fernandez, D, Gleisner, A, Perez, V, Codner, E. Tobacco, alcohol, and illicit drug use in adolescents with diabetes mellitus. Pediatr Diabetes 2007;8:265271.Google Scholar
Ng, RS, Darko, DA, Hillson, RM. Street drug use among young patients with type 1 diabetes in the UK. Diabet Med 2004;21:295296.Google Scholar
Lee, P, Greenfield, JR, Campbell, LV. ‘Mind the gap’ when managing ketoacidosis in type 1 diabetes. Diabetes Care 2008;31:e58.Google Scholar
Rattray, M. Ecstasy: towards an understanding of the biochemical basis of the action of MDMA. Essays Biochem 1991;26:77.Google Scholar
Britt, GC, McCance-Katz, EF. A brief overview of the clinical pharmacology of ‘club drugs’. Subst Use Misuse 2005;40:11891201.Google Scholar
Seymour, HR, Gilman, D, Quin, JD. Severe ketoacidosis complicated by ‘ecstasy’ ingestion and prolonged exercise. Diabet Med 1996;13:908909.Google Scholar
Giorgi, FS, Lazzeri, G, Natale, G, et al. MDMA and seizures: a dangerous liaison? Ann NY Acad Sci 2006;1074:357364.Google Scholar
Rosenson, J, Smollin, C, Sporer, KA, Blanc, P, Olson, KR. Patterns of ecstasy-associated hyponatremia in California. Ann Emerg Med 2007;49:164171.Google Scholar
Kalantar-Zadeh, K, Nguyen, MK, Chang, R, Kurtz, I. Fatal hyponatremia in a young woman after ecstasy ingestion. Nat Clin Pract Nephrol 2006;2:283288.Google Scholar
Ben-Abraham, R, Szold, O, Rudick, V, Weinbroum, AA. ‘Ecstasy’ intoxication: life-threatening manifestations and resuscitative measures in the intensive care setting. Eur J Emerg Med 2003;10:309313.Google Scholar
Brvar, M, Kozelj, G, Osredkar, J, Mozina, M, Gricar, M, Bunc, M. Polydipsia as another mechanism of hyponatremia after ‘ecstasy’ (3,4 methyldioxymethamphetamine) ingestion. Eur J Emerg Med 2004;11:302304.Google Scholar
Kwon, C, Zaritsky, A, Dharnidharka, VR. Transient proximal tubular renal injury following ecstasy ingestion. Pediatr Nephrol 2003;18:820822.Google Scholar
Lee, P, Nicoll, AJ, McDonough, M, Colman, PG. Substance abuse in young patients with type 1 diabetes: easily neglected in complex medical management. Intern Med J 2005;35:359361.Google Scholar
Rome, ES. It’s a rave new world: rave culture and illicit drug use in the young. Cleve Clin J Med 2001;68:541550.Google Scholar
Buchanan, JF, Brown, CR. ‘Designer drugs’. A problem in clinical toxicology. Med Toxicol Adverse Drug Exp 1988;3:1.Google Scholar
Koesters, SC, Rogers, PD, Rajasingham, CR. MDMA (‘ecstasy’) and other ‘club drugs’. The new epidemic. Paediatr Clin North Am 2002;49:415.Google Scholar
Lee, P, Campbell, LV. Diabetic ketoacidosis: the usual villain or a scapegoat? A novel cause of severe metabolic acidosis in type 1 diabetes. Diabetes Care 2008;31:e13.Google Scholar
Romanelli, F, Smith, KM, Pomeroy, C. Use of club drugs by HIV-seropositive and HIV-seronegative gay and bisexual men. Top HIV Med 2003;11(1):2532.Google Scholar
Morgan, CJ, Muetzelfeldt, L, Curran, HV. Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study. Addiction 2010;105:121133.Google Scholar
Morgan, CJ, Rossell, SL, Pepper, F, et al. Semantic priming after ketamine acutely in healthy volunteers and following chronic self-administration in substance users. Biol Psychiatry 2006;59:265272.Google Scholar
Morgan, CJ, Perry, EB, Cho, HS, Krystal, JH, D’Souza, DC. Greater vulnerability to the amnestic effects of ketamine in males. Psychopharmacology (Berl) 2006;187:405414.Google Scholar
Morgan, CJ, Muetzelfeldt, L, Curran, HV. Ketamine use, cognition and psychological wellbeing: a comparison of frequent, infrequent and ex-users with polydrug and non-using controls. Addiction 2009;104:7787.Google Scholar
Morgan, CJ, Monaghan, L, Curran, HV. Beyond the K-hole: a 3-year longitudinal investigation of the cognitive and subjective effects of ketamine in recreational users who have substantially reduced their use of the drug. Addiction 2004;99(11):14501461.Google Scholar
Narendran, R, Frankle, WG, Keefe, R, et al. Altered prefrontal dopaminergic function in chronic recreational ketamine users. Am J Psychiatry 2005;162:23522359.Google Scholar
Aan het Rot, M, Collins, KA, Murrough, JW, et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry 2010;67:139145.Google Scholar
Womble, AL. Effects of ketamine on major depressive disorder in a patient with posttraumatic stress disorder. AANA J 2013;81(2):118119.Google Scholar
Berman, RM, Cappiello, A, Anand, A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000;47(4):351354.Google Scholar
Aan het, Rot M, Collins, KA, Murrough, JW, et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment resistant depression. Biol Psychiatry 2010;67:139145.Google Scholar
Womble, AL. Effects of ketamine on major depressive disorder in a patient with posttraumatic stress disorder. AANA J 2013;81(2):118119.Google Scholar
Murrough, JW. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site, randomized, parallel-arm, midazolam-controlled, clinical trial. Biol Psychiatry 2013;73(9 Suppl. 1):142S.Google Scholar
Zarate, CA, Singh, JB, Carlson, PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63(8):856864.Google Scholar
McGirr, A, Berlim, MT, Bond, DJ, Fleck, MP, Yatham, LN, Lam, RW. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med 2015;45(4):693704.Google Scholar
Iadarola, ND, Niciu, MJ, Richards, EM, et al. Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review. Ther Adv Chronic Dis 2015;6(3):97114.Google Scholar
Mathew, SJ, Zarate Jr, CA eds. Ketamine for Treatment-Resistant Depression: The First Decade of Progress. New York, Springer, 2016.Google Scholar
Singh, JB, Fedgchin, M, Daly, EJ, et al. A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. Am J Psychiatry 2016;173(8):816826.Google Scholar
Albott, C, Lim, K. Forbes, M, et al. 1001-Neurocognitive effects of repeated ketamine infusions in co-occurring posttraumatic stress disorder and treatment-resistant depression. Biol Psychiatry 2017;81(10):S405.Google Scholar
Al Shirawi, MI, Kennedy, SH, Ho, KT, Byrne, R, Downar, J. Oral ketamine in treatment-resistant depression: a clinical effectiveness case series. J Clin Psychopharmacol 2017;37(4):464467.Google Scholar
Singh, I, Morgan, C, Curran, V, Nutt, D, Schlag, A, McShane, R. Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight. Lancet Psychiatry 2017;4(5):419426.Google Scholar
Berman, RM, Cappiello, A, Anand, A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000;47(4):351354.Google Scholar
Zarate, CA, Singh, JB, Carlson, PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63(8):856864.Google Scholar
Krystal, JH. Ketamine and the potential role for rapid acting antidepressant medications. Swiss Med Wkly 2007;137:215216.Google Scholar
Schwartz J, , Murrough JW, , Iosifescu DV. Ketamine for treatment-resistant depression: recent developments and clinical applications. Evid Based Mental Health 2016 ;19(2):3538.Google Scholar
Mathew, SJ, Shah, A, Lapidus, K, et al. Ketamine for treatment-resistant unipolar depression. CNS Drugs 2012;26:189204.Google Scholar
Murrough, JW, Iosifescu, DV, Chang, LC, et al. An antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry 2013;170:11341142.Google Scholar
Fond, G, Loundou, A, Rabu, C, et al. Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology (Berl) 2014;231:36633676.Google Scholar
McGirr, A, Berlim, MT, Bond, DJ, et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med 2015;45:693704.Google Scholar
SchakJennifer KM, Van de Voort L, , Johnson EK, et al. Potential risks of poorly monitored ketamine use in depression treatment. Am J Psychiatry 2016;173:3.Google Scholar
Murrough, JW. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site, randomized, parallel-arm, midazolam-controlled, clinical trial. Biol Psychiatry 2013;73(9) Suppl. 1(142S).Google Scholar
Chang, H, Huang, MC, Chen, LY. Major depressive disorder induced by chronic ketamine abuse: a case report. Prim Care Companion CNS Disord 2016;18(3):10. https://doi.org/10.4088/PCC.15l01881Google Scholar
Liang HJ, , Tang KL, , Chan F, , Ungvari GS, , Tang KW., Ketamine users have high rates of psychosis and/or depression. J Addic Nurs 2015;26(1):813.Google Scholar
Liao, Y, Tang, J, Ma, M, et al. Frontal white matter abnormalities following chronic ketamine use: a diffusion tensor imaging study. Brain 2010;133:21152122.Google Scholar
Liao, Y, Tang, J, Corlett, PR, et al. Reduced dorsal prefrontal gray matter after chronic ketamine use. Biol Psychiatry 2011;69(1):4248. https://doi.org/10.1016/j.biopsych.2010.08.030Google Scholar
Maxwell, JC. The response to club drug use. Curr Opin Psychiatry 2003;16:279289.Google Scholar
Krystal, J, Karper, H, Bennett, LP, et al. Interactive effects of sub anaesthetic ketamine and subhypnotic lorazepam in humans. Psychopharmacology 1998;135:213229.Google Scholar
Bhad R, , Dayal P, , Kumar S, , Ambekar A. The drug ketamine: a double-edged sword for mental health professionals. J Subst Use 2016;21(4):341343https://doi.org/10.3109/14659891.2015.1040092Google Scholar
Pérez Gómez L, , González Martínez M, , González Fernández A, et al. Possible use of paliperidone palmitate in ketamine addiction. Eur Psychiatry 2015;30(Suppl. 1):1085. https://doi.org/10.1016/S0924-9338(15)30856-7Google Scholar
Huang M-C, , Chen L-Y, , Chen C-K, , Lin S-K., Potential benefit of lamotrigine in managing ketamine use disorder. Med Hypotheses 2016;87:97100. https://doi.org/10.1016/j.mehy.2015.11.011Google Scholar
Chang F, , Xu K, , Huang M-C, , Krystal J-H, . Alcohol triggers re-emergence of ketamine-like experience in a ketamine ex-user. J Clin Psychopharmacol 2017;37(1):110112. https://doi.org/10.1097/JCP.0000000000000635Google Scholar
de P. Ramos S, Zambonato TK, , Graziottin TM., Reduced functional bladder capacity associated with ketamine use. Braz J Psychiatry 2019;41(3):270271. https://doi:10.1590/1516-4446-2018-0314Google Scholar
de P. Ramos S, Zambonato TK, , Graziottin TM., Reduced functional bladder capacity associated with ketamine use. Braz J Psychiatry 2019;41(3):270271. https://doi:10.1590/1516-4446-2018-0314Google Scholar
de P. Ramos S, Zambonato TK, , Graziottin TM., Reduced functional bladder capacity associated with ketamine use. Braz J Psychiatry 2019;41(3):270271. https://doi:10.1590/1516-4446-2018-0314Google Scholar
Cottrell, AM, Gillat, DA. Ketamine-associated urinary pathology: the tip of the iceberg for urologists? Br J Med Surg Urol 2008;1:136138.Google Scholar
Robles-Martínez M, , Abad AC, Pérez-Rodríguez V, RosCucurull E, Esojo A, Roncero C. Delayed urinary symptoms induced by ketamine. J Psychoactive Drugs 2017 (online). https://doi.org/10.1080/02791072.2017.1371364Google Scholar
Winstock, AR, Mitcheson, L, Gillatt, DA, Cottrell, AM. The prevalence and natural history of urinary symptoms among recreational ketamine users. BJU Int 2012;110(11):17621766. https://doi.org/10.1111/j.1464-410X.2012.11028.xGoogle Scholar
Sihra N, , Ockrim J, , Wood D., The effects of recreational ketamine cystitis on urinary tract reconstruction – a surgical challenge. BJU Int 2018;121:458465.Google Scholar
Wood, D. Ketamine and damage to the urinary tract. Addiction 2013;108:15151519.Google Scholar
Robles-Martínez M, , Abad AC, , Pérez-Rodríguez V, , Cucurull ER, , Esojo A, , Roncero C., Delayed urinary symptoms induced by ketamine. J Psychoactive Drugs 2017 (online). https://doi.org/10.1080/02791072.2017.1371364Google Scholar
Sihra N, , Ockrim J, , Wood D., The effects of recreational ketamine cystitis on urinary tract reconstruction – a surgical challenge. BJU Int 2018;121:458465.Google Scholar
Sihra N, , Ockrim J, , Wood D., The effects of recreational ketamine cystitis on urinary tract reconstruction – a surgical challenge. BJU Int 2018;121:458465.Google Scholar
Siu, AMH, Mak SK., Ko FSL Outcome evaluation of a short-term hospitalization and community support program for people who abuse ketamine. Front Psychiatry 2018;9:313.Google Scholar
Lankenau, S, Clatts, M. Drug injection practices among high-risk youth: the first shot of ketamine. J Urban Health 2004;81(2):232248.Google Scholar
Lankenau, S, Clatts, M. Patterns of polydrug use among ketamine injectors in New York City. Subst Use Misuse 2005;40:13811397.Google Scholar
Lankenau, S, Sanders, B. Patterns and frequencies of ketamine injection in New York City. J Psychoactive Drug 2007;39(1):2129.Google Scholar
Cheng, WC, Ng, KM, Chan, KK, Mok, VK, Cheung, BK. Roadside detection of impairment under the influence of ketamine – evaluation of ketamine impairment symptoms with reference to its concentration in oral fluid and urine. Forensic Sci Int 2007;170:5158.Google Scholar
Giorgetti R, , Marcotulli D, , Tagliabrac A, , Schifano F., Effects of ketamine on psychomotor, sensory and cognitive functions relevant for driving ability. Forensic Sci Int 2015;252:127142. https://doi.org/10.1016/j.forsciint.2015.04.024Google Scholar
Cheng, JY, Chan, DT, Mok, VK. An epidemiological study on alcohol-/drugs-related fatal traffic crash cases of deceased drivers in Hong Kong between 1996 and 2000. Forensic Sci Int 2005;153:196201.Google Scholar
Fassette T, , Martinez A, . An impaired driver found to be under the influence of methoxetamine. J Anal Toxicol 2016;40(8):700702https://doi.org/10.1093/jat/bkw054Google Scholar
Scott-Ham, M, Burton, FC. Toxicological findings in cases of alleged drug-facilitated sexual assault in the United Kingdom over a 3-year period. J Clin Forensic Med 2005;12:175186.Google Scholar
Du Mont, J, Macdonald, S, Rotbard, N, et al. Drug-facilitated sexual assault in Ontario, Canada: toxicological and DNA findings. J Forensic Leg Med 2010;17:333338.Google Scholar

References

Savage, S, Daqing, MD. The neurotoxicity of nitrous oxide: the facts and ‘putative’ mechanisms. Brain Sci 2014;4:7390. https://doi.org/10.3390/brainsci4010073Google Scholar
Berkowitz, BA, Finck, AD, Ngai, SH. Nitrous oxide analgesia: reversal by naloxone and development of tolerance. J Pharmacol Exp Ther 1977;203:539547.Google Scholar
Savage, S, Daqing, MD. The neurotoxicity of nitrous oxide: the facts and ‘putative’ mechanisms. Brain Sci 2014;4:7390. https://doi.org/10.3390/brainsci4010073Google Scholar
Brouette, T, Anton, R. Clinical review of inhalants. Am J Addict 2001;10(1):7994.Google Scholar
Brouette, T, Anton, R. Clinical review of inhalants. Am J Addict 2001;10(1):7994.Google Scholar
Ghobrial, GM, Dalyai, R, Flanders, AE, Harrop, J. Nitrous oxide myelopathy posing as spinal cord injury. J Neurosurg Spine 2012;16(5):489491. https://doi.org/10.3171/2012.2.SPINE11532Google Scholar
Nunn, JF. Clinical aspects of the interaction between nitrous oxide and vitamin B12. Br J Anaesthesia 1987;59(1):313.Google Scholar
Amsterdama J, , den Brink W, . Recreational nitrous oxide use: prevalence and risks. Regul Toxicol Pharmacol 2015;73(3):790796.Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Consideration of the Novel Psychoactive Substances (Legal Highs). London, Home Office, October 2011.Google Scholar
Garakani, A, Jaffe, RJ, Savla, D, et al. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: a systematic review of the case literature. Am J Addict 2016;25:358369.Google Scholar
Gillman, MA, Lichtigfeld, FJ, Young, TN. Psychotropic analgesic nitrous oxide for alcoholic withdrawal states. Cochrane Database Syst Rev 2007;18(2):CD005190.Google Scholar
Kripke, BJ, Hechtman, HB. Nitrous oxide for pentazocine addiction and for intractable pain: report of case. Anesth Analg 1972;51(4):520527.Google Scholar
Lichtigfeld, FJ, Gillman, MA. The treatment of alcoholic withdrawal states with oxygen and nitrous oxide. S Afr Med J 1982;61(10):349351.Google Scholar
Gillman, MA, Lichtigfeld, FJ. Analgesic nitrous oxide: adjunct to clonidine for opioid withdrawal. Am J Psychiatry 1985;142(6):784785.Google Scholar
Carey, C, Clark, A, Saner, A. Excellent results with analgesic nitrous oxide for addictive withdrawal states in general practice. S Afr Med J 1991;79(8):516.Google Scholar
Alho, H, Methuen, T, Paloheimo, M, et al. Nitrous oxide has no effect in the treatment of alcohol withdrawal syndrome: a double-blind placebo-controlled randomized trial. J Clin Psychopharmacol 2003;23(2):211214.Google Scholar
Sanders, RD, Weimann, J, Maze, M. Biologic effects of nitrous oxide: a mechanistic and toxicologic review. Anesthesiology 2008;109(4):707722.Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Consideration of the Novel Psychoactive Substances (Legal Highs). London, Home Office, October 2011.Google Scholar
Kaar, SJ, Ferris, J, Waldron, J, Devaney, M, Ramsey, J, Winstock, AR. Up: the rise of nitrous oxide abuse. An international survey of contemporary nitrous oxide use. J Psychopharmacol 2016(online). https://doi.org/10.1177/0269881116632375Google Scholar
Chen, R, Liao, M, Ou, J. Laughing gas inhalation in Chinese youth: a public health issue. Lancet Public Health 2018;3(10):e465. https://doi.org/10.1016/S2468-2667(18)30134-8Google Scholar
Gillman, M. Polydrug abuse associated with nitrous oxide causes death. Oxf Med Case Reports 2016;6:117.Google Scholar
Mancke, F, Kaklauskaite, G, Kollmer, J, Weiler, M. Psychiatric comorbidities in a young man with subacute myelopathy induced by abusive nitrous oxide consumption: a case report Subst Abuse Rehab 2016;7:155159.Google Scholar
van Amsterdam, J, den Brink, W. Recreational nitrous oxide use: prevalence and risks. Reg Toxicol Pharmacol 2015;73(3):790796.Google Scholar
van Amsterdam, J, den Brink, W. Recreational nitrous oxide use: prevalence and risks. Reg Toxicol Pharmacol 2015;73(3):790796.Google Scholar
Cheng, HM, Park, JH, Hernstadt, D. Subacute combined degeneration of the spinal cord following recreational nitrous oxide use. BMJ Case Rep 2013;8: bcr2012008509. https://doi.org/10.1136/ bcr-2012-008509Google Scholar
Ng, J, O’Grady, G, Pettit, T, et al. Nitrous oxide use in first-year students at Auckland University. Lancet 2003;361:13491350.Google Scholar
Cheng, HM, Park, JH, Hernstadt, D. Subacute combined degeneration of the spinal cord following recreational nitrous oxide use. BMJ Case Rep 2013;8: bcr2012008509. https://doi.org/10.1136/ bcr-2012-008509Google Scholar
Ng, J, O’Grady, G, Pettit, T, et al. Nitrous oxide use in first-year students at Auckland University. Lancet 2003;361:13491350.Google Scholar
Wackawik, A, Luzzio, C, Juhasz-Poscine, K, et al. Myelo-neuropathy from nitrous oxide abuse: unusually high methylmalonic acid and homocysteine level. Wis Med J 2003;102:4345.Google Scholar
Gillman, MA. Nitrous oxide abuse in perspective. Clin Neuropharmacol 1992;15:297306.Google Scholar
Cartner, M, Sinnott, M, Silburn, P. Paralysis caused by ‘nagging’. Med J Aust 2007;187:366367.Google Scholar
Alt, RS, Morrissey, RP, Gang, MA, et al. Severe myeloneuropathy from acute high-dose nitrous oxide(N2O) abuse. J Emerg Med 2011;41:378380.Google Scholar
Miller, MA, Martinez, V, McCarthy, R, et al. Nitrous oxide ‘whippit’ abuse presenting as clinical B12 deficiency and ataxia. Am J Emerg Med 2004;22:124.Google Scholar
Shulman, RM, Geraghty, TJ, Tadros, M. A case of unusual substance abuse causing myeloneuropathy. Spinal Cord 2007;45:314317.Google Scholar
Ng, J, Nanging FR, . Lancet 2002;360(9330):384.Google Scholar
Tatum, WO, Bui, DD, Grant, EG, et al. Pseudo-Guillain-Barre syndrome due to ‘whippet’-induced myeloneuropathy. J Neuroimaging 2010;20:400401.Google Scholar
Lin, RJ, Chen, HF, Chang, YC, et al. Subacute combined degeneration caused by nitrous oxide intoxication: case reports. Acta Neurol Taiwan 2011;20:129137.Google Scholar
Vasconcelos, OM, Poehm, EH, McCarter, RJ, et al. Potential outcome factors in subacute combined degeneration: review of observational studies. J Gen Intern Med 2006;21:10631068.Google Scholar
Dohrn, CS, Lichtor, JL, Finn, RS, et al. Subjective and psychomotor effects of nitrous oxide in healthy volunteers. Behav Pharmacol 1992;3(1):1930.Google Scholar
Sanders, RD, Weimann, J, Maze, M. Biologic effects of nitrous oxide: a mechanistic and toxicologic review. Anesthesiology 2008;109(4):707722.Google Scholar
van Amsterdam, J, Nabben, T, van den Brink W. Recreational nitrous oxide use: prevalence and risks. Regul Toxicol Pharmacol 2015;73(3):790796.Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Consideration of the Novel Psychoactive Substances (Legal Highs). London, Home Office, October 2011.Google Scholar
Lichtigfeld, FJ, Gillman, MA. The treatment of alcoholic withdrawal states with oxygen and nitrous oxide. S Afr Med J 1982;61(10):349351.Google Scholar
Glijn, NHP, van der Linde, D, Ertekin, E, van Burg, PLM, Grimbergen, YAM, Libourel, EJ. Is nitrous oxide really that joyful? Neth J Med 2017;75(7):304306.Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Consideration of the Novel Psychoactive Substances (Legal Highs). London, Home Office, October 2011.Google Scholar
Lichtigfeld, FJ, Gillman, MA. The treatment of alcoholic withdrawal states with oxygen and nitrous oxide. S Afr Med J 1982;61(10):349351.Google Scholar
Glijn, NHP, van der Linde, D, Ertekin, E, van Burg, PLM, Grimbergen, YAM, Libourel, EJ. Is nitrous oxide really that joyful? Neth J Med 2017;75(7):304306.Google Scholar
Kaar, SJ, Ferris, J, Waldron, J, Devaney, M, Ramsey, J, Winstock, AR. Up: the rise of nitrous oxide abuse. An international survey of contemporary nitrous oxide use. J Psychopharmacol 2016(online). https://doi.org/10.1177/0269881116632375Google Scholar
Lundin, MS, Cherian, J, Andrew, MN, et al. One month of nitrous oxide abuse causing acute vitamin B 12 deficiency with severe neuropsychiatric symptoms BMJ Case Reports CP 2019;12:bcr-2018-228001.Google Scholar
Lundin, MS, Cherian, J, Andrew, MN, et al. One month of nitrous oxide abuse causing acute vitamin B 12 deficiency with severe neuropsychiatric symptoms BMJ Case Reports CP 2019;12:bcr-2018-228001.Google Scholar
Walker, DJ, Zacny, JP. Within- and between-subject variability in the reinforcing and subjective effects of nitrous oxide in healthy volunteers. Drug Alcohol Depend 2001;64(1):8596.Google Scholar
Walker, DJ, Zacny, JP. Within- and between-subject variability in the reinforcing and subjective effects of nitrous oxide in healthy volunteers. Drug Alcohol Depend 2001;64(1):8596.Google Scholar
Dohrn, CS, Lichtor, JL, Finn, RS, et al. Subjective and psychomotor effects of nitrous oxide in healthy volunteers. Behav Pharmacol 1992;3(1):1930.Google Scholar
Zacny, JP, Jun, JM. Lack of sex differences to the subjective effects of nitrous oxide in healthy volunteers. Drug Alcohol Depend 2010;112(3):251254.Google Scholar
van Amsterdam, J, den Brink, W. Recreational nitrous oxide use: prevalence and risks. Reg Toxicol Pharmacol 2015;73(3):790796.Google Scholar
Bennett, CR. Nitrous oxide hallucinations. J Am Dent Assoc 1980;101:595597.Google Scholar
Jastak, JT, Malamed, SF. Nitrous oxide sedation and sexual phenomena. J Am Dent Assoc 1980;101:3840.Google Scholar
Lambert, C. Sexual phenomena hypnosis and nitrous oxide sedation. J Am Dent Assoc 1982;105:990991.Google Scholar
Lichtigfeld, FJ, Gillman, MA. The treatment of alcoholic withdrawal states with oxygen and nitrous oxide. S Afr Med J 1982;61(10):349351.Google Scholar
Randhawa, G, Bodenham, A. The increasing recreational use of nitrous oxide: history revisited. Br J Anaesth 2016;116(3):321324. https://doi.org/10.1093/bja/aev297Google Scholar
Wagner, SA, Clark, MA, Wesche, DL, Doedens, DJ, Lloyd, AW. Asphyxial deaths from the recreational use of nitrous oxide. J Forensic Sci 1992;37(4):10081015.Google Scholar
Gillman, M. Polydrug abuse associated with nitrous oxide causes death. Oxf Med Case Reports 2016;2016(6):117.Google Scholar
Advisory Council on the Misuse of Drugs (ACMD). Consideration of the Novel Psychoactive Substances (Legal Highs). London, Home Office, October 2011.Google Scholar
Garakani, A, Jaffe, RJ, Savla, D, et al. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: a systematic review of the case literature. Am J Addict 2016;25:358369.Google Scholar
Dohrn, CS, Lichtor, JL, Finn, RS, et al. Subjective and psychomotor effects of nitrous oxide in healthy volunteers. Behav Pharmacol 1992;3(1):1930.Google Scholar
Hwang, JC, Himel, HN, Edlich, RF. Frostbite of the face after recreational misuse of nitrous oxide. Burns 1996;22(2):152153.Google Scholar
Brouette, T, Anton, R. Clinical review of inhalants. Am J Addict 2001;10(1):7994.Google Scholar
Sanders, RD, Weimann, J, Maze, M. Biologic effects of nitrous oxide: a mechanistic and toxicologic review. Anesthesiology 2008;109(4):707722.Google Scholar
Rosenberg, H, Orkin, FK, Springstead, J. Abuse of nitrous oxide. Anesth Analg 1979;58(2):104106.Google Scholar
Ghobrial, GM, Dalyai, R, Flanders, AE, Harrop, J. Nitrous oxide myelopathy posing as spinal cord injury. J Neurosurg Spine 2012;16(5):489491. https://doi.org/10.3171/2012.2.SPINE11532Google Scholar
Chadly, A, Marc, B, Barres, D, Durigon, M. Suicide by nitrous oxide poisoning. Am J Forensic Med Pathol 1989;10(4):330331.Google Scholar
Suruda, AJ, McGlothlin, JD. Fatal abuse of nitrous oxide in the workplace. J Occup Med 1990;32(8):682684.Google Scholar
Pasternak, JJ, Lanier, WL. Is nitrous oxide use appropriate in neurosurgical and neurologically at-risk patients? Curr Opin Anaesthesiol 2010;23(5):544550.Google Scholar
Sanders, RD, Weimann, J, Maze, M. Biologic effects of nitrous oxide: a mechanistic and toxicologic review. Anesthesiology 2008;109(4):707722.Google Scholar
Randhawa, G, Bodenham, A. The increasing recreational use of nitrous oxide: history revisited. Br J Anaesth 2016;116(3):321324. https://doi.org/10.1093/bja/aev297Google Scholar
Garakani, A, Jaffe, RJ, Savla, D, et al. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: a systematic review of the case literature. Am J Addict 2016;25:358369.Google Scholar
Rosenberg, H, Orkin, FK, Springstead, J. Abuse of nitrous oxide. Anesth Analg 1979;58(2):104106.Google Scholar
Zacny, JP, Walker, DJ, Derus, LM. Choice of nitrous oxide and its subjective effects in light and moderate drinkers. Drug Alcohol Depend 2008;98(1–2):163168.Google Scholar
Mancke, F, Kaklauskaite, G, Kollmer, J, Weiler, M. Psychiatric comorbidities in a young man with subacute myelopathy induced by abusive nitrous oxide consumption: a case report. Subst Abuse Rehab 2016:7:155159.Google Scholar
Sheldon, R, Reid, M, Schon, F, Poole, N. Just say N2O – nitrous oxide misuse: essential information for psychiatrists. BJPsych Advances 2020;26(2):7281. https://doi.org/10.1192/bja.2019.57Google Scholar
van Amsterdam, J, den Brink, W. Recreational nitrous oxide use: prevalence and risks. Regul Toxicol Pharmacol 2015;73(3):790796.Google Scholar
Gillman, MA. Nitrous oxide abuse in perspective. Clin Neuropharmacol 1992;15:297306.Google Scholar
Gilman, MA. Nitrous oxide – an opioid agent: review of the evidence. Am J Med 1986; 81:97102.Google Scholar
Mancke, F, Kaklauskaite, G, Kollmer, J, Weiler, M. Psychiatric comorbidities in a young man with subacute myelopathy induced by abusive nitrous oxide consumption: a case report. Subst Abuse Rehab 2016;7:155159.Google Scholar
Tym, MK, Alexander, J. Nitrous oxide induced manic relapse. Aust NZ J Psychiatry 2011;45(11):1002.Google Scholar
Sethi, NK, Mullin, P, Torgovnick, J, Capasso, G. Nitrous oxide ‘whippit’ abuse presenting with cobalamin responsive psychosis. J Med Toxicol 2006;2(2):7174.Google Scholar
Cousaert, C, Heylens, G, Audenaert, K. Laughing gas abuse is no joke: an overview of the implications for psychiatric practice. Clin Neurol Neurosurg 2013;115(7):859862.Google Scholar
Garakani, A, Jaffe, RJ, Savla, D, et al. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: a systematic review of the case literature. Am J Addict 2016;25:358369.Google Scholar
Miller, MA, Martinez, V, McCarthy, R, et al. Nitrous oxide ‘whippit’ abuse presenting as clinical B12 deficiency and ataxia. Am J Emerg Med 2004;22:124.Google Scholar
Stacy, CB, Di Rocco, A, Gould, RJ. Methionine in the treatment of nitrous-oxide-induced neuropathy and myeloneuropathy. J Neurol 1992;239:401403.Google Scholar
Luis-Ferdinand, RT. Myelotoxic, neurotoxic and reproductive adverse effects of nitrous oxide. Adverse Drug React Toxicol Rev 1994;13:193206.Google Scholar
Al-Sadawi, M, Hidalgo, C, Chinyere, A, Apoorva, J, Modupe, O, McFarlane, SI. Inhaled nitrous oxide ‘whip-its!’ causing subacute combined degeneration of spinal cord. Am J Med Case Rep 2018;6(12):237240. https://doi.org/10.12691/ajmcr-6-12-3Google Scholar
Van Amsterdam, J, Nabben, T, van den Brink, W. Recreational nitrous oxide use: prevalence and risks. Regul Toxicol Pharmacol 2015;73:790796.Google Scholar
Stabler, SP. Vitamin B12 deficiency. N Engl J Med 2013;368:20412042.Google Scholar
Massey, TH, Pickersgill, TT, Peal, KJ. Nitrous oxide misuse and vitamin B12 deficiency. BMJ Case Rep 2016 (online). https://doi.org/10.1136/bcr-2016-215728Google Scholar
Cartner, M, Sinnott, M, Silburn, P. Paralysis caused by ‘nagging’. Med J Aust 2007;187:366367.Google Scholar
Garakani, A, Jaffe, RJ, Savla, D, et al. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: a systematic review of the case literature. Am J Addict 2016;25:358369.Google Scholar
Oussalah, A, Julien, M, Levy, J, et al. Global burden related to nitrous oxide exposure in medical and recreational settings: a systematic review and individual patient data meta-analysis. J Clin Med 2019;8:551.Google Scholar
Oussalah, A, Julien, M, Levy, J, et al. Global burden related to nitrous oxide exposure in medical and recreational settings: a systematic review and individual patient data meta-analysis. J Clin Med 2019;8:551.Google Scholar
van Amsterdam, J, van den Brink, W. Recreational nitrous oxide use: prevalence and risks. Regul Toxicol Pharmacol 2015;73(3):790796.Google Scholar
Richardson, PG. Peripheral neuropathy following nitrous oxide abuse. Emerg Med Australas 2010;22(1):8890.Google Scholar
Ghobrial, GM, Dalyai, R, Flanders, AE, Harrop, J. Nitrous oxide myelopathy posing as spinal cord injury. J Neurosurg Spine 2012;16(5):489491. https://doi.org/10.3171/2012.2.SPINE11532Google Scholar
Cheng, HM, Park, JH, Hernstadt, D. Subacute combined degeneration of the spinal cord following recreational nitrous oxide use. BMJ Case Rep 2013;8:bcr2012008509. https://doi.org/10.1136/ bcr-2012-008509Google Scholar
Miller, MA, Martinez, V, McCarthy, R, et al. Nitrous oxide ‘whippit’ abuse presenting as clinical B12 deficiency and ataxia. Am J Emerg Med 2004;22:124.Google Scholar
Shulman, RM, Geraghty, TJ, Tadros, M. A case of unusual substance abuse causing myeloneuropathy. Spinal Cord 2007;45:314317.Google Scholar
Tatum, WO, Bui, DD, Grant, EG, et al. Pseudo-Guillain-Barre syndrome due to ‘whippet’-induced myeloneuropathy. J Neuroimaging 2010;20:400401.Google Scholar
Richardson, PG. Peripheral neuropathy following nitrous oxide abuse. Emerg Med Australas 2010;22(1):8890.Google Scholar
Diamond, AL, Diamond, R, Freedman, SM, Thomas, FP. ‘Whippets’-induced cobalamin deficiency manifesting as cervical myelopathy. J Neuroimaging 2004;14(3):277280.Google Scholar
Hsu, CK, Chen, YQ, Lung, VZ, His, SC, Lo, HC, Shyu, HY. Myelopathy and polyneuropathy caused by nitrous oxide toxicity: a case report. Am J Emerg Med 2012;30(6):1016.e36. https://doi.org/10.1016/j. ajem.2011.05.001CrossRefGoogle ScholarPubMed
Probasco, JC, Felling, RJ, Carson, JT, Dorsey, ER, Niessen, TM. Teaching neuroimages: myelopathy due to B12 deficiency in long-term colchicine treatment and nitrous oxide misuse. Neurology 2011;77(9):e51. https://doi.org/10.1212/WNL.0b013e31822c910fGoogle Scholar
Sotirchos, ES, Saidha, S, Becker, D. Neurological picture: nitrous oxide-induced myelopathy with inverted V-sign on spinal MRI. J Neurol Neurosurg Psychiatry 2012;83(9):915916.Google Scholar
Waters, MF, Kang, GA, Mazziotta, JC, DeGiorgio, CM. Nitrous oxide inhalation as a cause of cervical myelopathy. Acta Neurol Scand 2005;12(4):270272.Google Scholar
Massey, TH, Pickersgill, TT, Peall, JK. Nitrous oxide misuse and vitamin B12 deficiency. Case Rep 2016;2016: bcr2016215728.Google Scholar
Richardson, PG. Peripheral neuropathy following nitrous oxide abuse. Emerg Med Australas 2010;22(1):8890.CrossRefGoogle ScholarPubMed
Miller, MA, Martinez, V, McCarthy, R, et al. Nitrous oxide ‘whippit’ abuse presenting as clinical B12 deficiency and ataxia. Am J Emerg Med 2004;22:124.CrossRefGoogle ScholarPubMed
Dong X, Ba F, Wang R, , Zheng D. Imaging appearance of myelopathy secondary to nitrous oxide abuse: a case report and review of the literature. Int J Neurosci 2019;129(3):225229https://doi.org/10.1080/00207454.2018.1526801Google Scholar
Williamson, J, Huda, S, Damodaran, D. Nitrous oxide myelopathy with functional vitamin B 12 deficiency. BMJ Case Rep CP 2019;12:e227439.Google Scholar
Miller, MA, Martinez, V, McCarthy, R, et al. Nitrous oxide ‘whippit’ abuse presenting as clinical B12 deficiency and ataxia. Am J Emerg Med 2004;22:124.Google Scholar
Glijn, NHP, van der Linde, D, Ertekin, E, van Burg, PLM, Grimbergen, YAM, Libourel, EJ. Is nitrous oxide really that joyful? Neth J Med 2017;75(7):304306.Google Scholar
Garriott, J, Petty, CS. Death from inhalant abuse: toxicological and pathological evaluation of 34 cases. Clin Toxicol 1980;16:305315.Google Scholar
Bowen, SE, Daniel, J, Balster, RL. Deaths associated with inhalant abuse in Virginia from 1987 to 1996. Drug Alcohol Depend 1999;53:239245.Google Scholar
Suruda, AJ, McGlothlin, JD. Fatal abuse of nitrous oxide in the workplace. J Occup Med 1990;32:682684.Google Scholar
Winstock, AR. Ferris, JA. Nitrous oxide causes peripheral neuropathy in a dose-dependent manner among recreational users. J Psychopharmacol 2020;34(2):229236https://doi.org/10.1177/0269881119882532Google Scholar
Garakani, A, Jaffe, RJ, Savla, D, et al. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: a systematic review of the case literature. Am J Addict 2016;25:358369.Google Scholar
Stabler, SP. Vitamin B12 deficiency. N Engl J Med 2013;368:20412042.Google Scholar
Massey, TH, Pickersgill, TT, Peal, KJ. Nitrous oxide misuse and Vitamin B12 deficiency. BMJ Case Rep 2016 (online). https://doi.org/10.1136/bcr-2016-215728Google Scholar
Mishra, VA, Harbada, R, Sharma, A. Vitamin B12 and vitamin D deficiencies: an unusual cause of fever, severe hemolytic anemia and thrombocytopenia. J Fam Med Prim Care 2015;4:145148.Google Scholar
Carey, C, Clark, A, Saner, A. Excellent results with analgesic nitrous oxide for addictive withdrawal states in general practice. S Afr Med J 1991;79(8):516.Google Scholar
Cheng, HM, Park, JH, Hernstadt, D. Subacute combined degeneration of the spinal cord following recreational nitrous oxide use. BMJ Case Rep 2013;2013:bcr2012008509. https://doi.org/10.1136/ bcr-2012-008509Google Scholar
Randhawa, G, Bodenham, A. The increasing recreational use of nitrous oxide: history revisited. Br J Anaesthesia 2016;116(3):321324. https://doi.org/10.1093/bja/aev297Google Scholar
Cartner, M, Sinnott, M, Silburn, P. Paralysis caused by ‘nagging’. Med J Aust 2007;187:366367.CrossRefGoogle ScholarPubMed
Sethi, NK, Mullin, P, Torgovnick, J, Capasso, G. Nitrous oxide ‘whippit’ abuse presenting with cobalamin responsive psychosis. J Med Toxicol 2006;2(2):7174.Google Scholar
Al-Sadawi, M, Hidalgo, C, Chinyere, A, Apoorva, J, Modupe, O, McFarlane, SI. Inhaled nitrous oxide ‘whip-its!’ causing subacute combined degeneration of spinal cord. Am J Med Case Rep 2018;6(12):237240. https://doi.org/10.12691/ajmcr-6-12-3Google Scholar
Massey, TH, Pickersgill, TT, Peal, KJ. Nitrous oxide misuse and Vitamin B12 deficiency. BMJ Case Rep 2016 (online). https://doi.org/10.1136/bcr-2016-215728Google Scholar
Miller, MA, Martinez, V, McCarthy, R, et al. Nitrous oxide ‘whippit’ abuse presenting as clinical B12 deficiency and ataxia. Am J Emerg Med 2004;22:124.Google Scholar
Butzkueven, H, King, JO. Nitrous oxide myelopathy in an abuser of whipped cream bulbs. J Clin Neurosci 2000;7(1):7375.Google Scholar
Cheng, HM, Park, JH, Hernstadt, D. Subacute combined degeneration of the spinal cord following recreational nitrous oxide use. BMJ Case Rep 2013;2013:bcr2012008509. https://doi.org/10.1136/ bcr-2012-008509Google Scholar
Miller, MA, Martinez, V, McCarthy, R, et al. Nitrous oxide ‘whippit’ abuse presenting as clinical B12 deficiency and ataxia. Am J Emerg Med 2004;22:124.Google Scholar
Richardson, PG. Peripheral neuropathy following nitrous oxide abuse. Emerg Med Australas 2010;22(1):8890.Google Scholar
Diamond, AL, Diamond, R, Freedman, SM, Thomas, FP. ‘Whippets’-induced cobalamin deficiency manifesting as cervical myelopathy. J Neuroimaging 2004;14(3):277280.Google Scholar
Probasco, JC, Felling, RJ, Carson, JT, Dorsey, ER, Niessen, TM. Teaching neuroimages: myelopathy due to B12 deficiency in long-term colchicine treatment and nitrous oxide misuse. Neurology 2011;77(9):e51. https://doi.org/10.1212/WNL.0b013e31822c910fGoogle Scholar
Ghobrial, GM, Dalyai, R, Flanders, AE, Harrop, J. Nitrous oxide myelopathy posing as spinal cord injury. J Neurosurg Spine 2012;16(5):489491. https://doi.org/10.3171/2012.2.SPINE11532Google Scholar
Lundin, MS, Cherian, J, Andrew, MN, et al. One month of nitrous oxide abuse causing acute vitamin B 12 deficiency with severe neuropsychiatric symptoms BMJ Case Rep 2019;12:bcr–2018–228001.Google Scholar
Diamond, AL, Diamond, R, Freedman, SM, Thomas, FP. ‘Whippets’-induced cobalamin deficiency manifesting as cervical myelopathy. J Neuroimaging 2004;14(3):277280.Google Scholar
Thompson, AG, Leite, MI, Lunn, MP, Bennett DLH. Whippits, nitrous oxide and the dangers of legal highs. Pract Neurol 2015;15:207209. https://doi.org/10.1136/practneurol-2014-001071Google Scholar
Keddie, S, Adams, A, Kelso, ARC, et al. No laughing matter: subacute degeneration of the spinal cord due to nitrous oxide inhalation J Neurol 2018;265:10891095. https://doi.org/10.1007/s00415-018-8801-3Google Scholar
Vasconcelos, OM, Poehm, EH, McCarter, RJ, Campbell, WW, Quezado, ZMN. Potential outcome factors in subacute combined degeneration: review of observational studies. J Gen Intern Med 2006;21:10631068.CrossRefGoogle ScholarPubMed
Massey, TH, Pickersgill, TT, Peal, KJ. Nitrous oxide misuse and Vitamin B12 deficiency. BMJ Case Rep 2016 (online). https://doi.org/10.1136/bcr-2016-215728Google Scholar
Shoults, K. Case report: neurological complications of nitrous oxide abuse. B C Med J 2016;58(4):192194.Google Scholar
Vasconcelos, OM, Poehm, EH, McCarter, RJ, Campbell, WW, Quezado, ZMN. Potential outcome factors in subacute combined degeneration: review of observational studies. J Gen Intern Med 2006;21:10631068.Google Scholar
Keddie, S, Adams, A, Kelso, ARC, et al. No laughing matter: subacute degeneration of the spinal cord due to nitrous oxide inhalation. J Neurol 2018; 265:10891095. https://doi.org/10.1007/s00415-018-8801-3Google Scholar
Blair, C, Tremonti, C, Edwards, L, Haber, PS, Halmagyi, GM. Vitamin B12 supplementation futile for preventing demyelination in ongoing nitrous oxide misuse Med J Aust 2019;211(9):428https://doi.org/10.5694/mja2.50371Google Scholar
Stacy, C, DiRocco, A, Gould, R. Methionine in the treatment of nitrous oxide induced neuropathy and myeloneuroapthy. J Neurol 1992;239(7):401403.Google Scholar
Ives, R, Ghelani, P. Polydrug use (the use of drugs in combination): a brief review. Drugs Educ Prev Policy 2006;13(3):225232.Google Scholar
Mancke, F, Kaklauskaite, G, Kollmer, J, Weiler, M. Psychiatric comorbidities in a young man with subacute myelopathy induced by abusive nitrous oxide consumption: a case report. Subst Abuse Rehab 2016:7 155159.Google Scholar
Garakani, A, Jaffe, RJ, Savla, D, et al. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: a systematic review of the case literature. Am J Addict 2016;25:358369.Google Scholar
Garakani, A, Jaffe, RJ, Savla, D, et al. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: a systematic review of the case literature. Am J Addict 2016;25:358369.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×