Evaluating the risk of toxicity and adverse drug interactions involving recreational GHB use and prescribed drugs

References

• Busardò FP, Kyriakou C, Napoletano S, et al. Clinical applications of sodium oxybate (GHB): from narcolepsy to alcohol withdrawal syndrome. Eur Rev Med Pharmacol Sci. 2015;19:4654–4663.
   PubMed Web of Science ®Google Scholar
• Deveaux M, Renet S, Renet V, et al. Utilisation de l’acide gamma-hydroxybutyrique (GHB) dans les rave-parties et pour la soumission chimique en France: mythe ou réalité? Acta Clin Belg. 2002;57(1):37–40.
   Google Scholar
• Wong CGT, Chan KFY, Gibson KM, et al. Gamma-hydroxybutyric acid: neurobiology and toxicology of a recreational drug. Toxicol Rev. 2004;23:3–20.
   PubMedGoogle Scholar
• Snead OC, Gibson KM. Gamma-hydroxybutyric acid. N Engl J Med. 2005;352:2721–2732.
   PubMed Web of Science ®Google Scholar
• Tillakaratne NJK, Medina-Kauwe L, Gibson KM. Gamma-aminobutyric acid (GABA) metabolism in mammalian neural and nonneural tissues. Comp Biochem Physiol A Physiol. 1995;112:247–263.
   PubMedGoogle Scholar
• Karila L, Reynaud M. GHB and synthetic cathinones: clinical effects and potential consequences. Drug Test Anal. 2011;3:552–559.
   PubMed Web of Science ®Google Scholar
• Felmlee MA, Morse BL, Morris ME. γ-Hydroxybutyric acid: pharmacokinetics, pharmacodynamics, and toxicology. AAPS J. 2021;23:22.
   PubMed Web of Science ®Google Scholar
• Jarsiah P, Roehrich J, Kueting T, et al. GHB related acids are useful in routine casework of suspected GHB intoxication cases. Forensic Sci Int. 2021;324:110833.
   PubMedGoogle Scholar
• Busardò FP, Bertol E, Vaiano F, et al. Post mortem concentrations of endogenous gamma hydroxybutyric acid (GHB) and in vitro formation in stored blood and urine samples. Forensic Sci Int. 2014;243:144–148.
   PubMed Web of Science ®Google Scholar
• Brennan R, Van Hout MC. Gamma-hydroxybutyrate (GHB): a scoping review of pharmacology, toxicology, motives for use, and user groups. J Psychoactive Drugs. 2014;46:243–251.
   PubMed Web of Science ®Google Scholar
• Ricaurte GA, McCann UD. Recognition and management of complications of new recreational drug use. Lancet. 2005;365:2137–2145.
   PubMed Web of Science ®Google Scholar
• Andresen H, Stimpfl T, Sprys N, et al. Liquid ecstasy - a significant drug problem. Dtsch Arztebl Int. 2008;105:599–603.
   PubMed Web of Science ®Google Scholar
• Drasbek KR, Christensen J, Jensen K. Gamma-hydroxybutyrate - A drug of abuse. Acta Neurol Scand. 2006;114:145–156.
   PubMed Web of Science ®Google Scholar
• Schep LJ, Knudsen K, Slaughter RJ, et al. The clinical toxicology of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4-butanediol. Clin Toxicol (Phila). 2012;50:458–470.
   PubMed Web of Science ®Google Scholar
• Hanisch S, Stachel N, Skopp G. A potential new metabolite of gamma-hydroxybutyrate: sulfonated gamma-hydroxybutyric acid. Int J Legal Med. 2016;130:411–414.
   PubMed Web of Science ®Google Scholar
• Marchei E, Tini A, Pirani F, et al. Is GHB-glucuronide useful as a biomarker for the exogenous use of GHB? Eur Rev Med Pharmacol Sci. 2019;23:2311–2313.
   PubMed Web of Science ®Google Scholar
• Gable RS. Acute toxic effects of club drugs. J Psychoactive Drugs. 2004;36:303–313.
   PubMed Web of Science ®Google Scholar
• Iven VG. Recreational drugs. Clin Sports Med. 1998;17:245–259.
   PubMed Web of Science ®Google Scholar
• Guerreiro DF, Carmo AL, Da Silva JA, et al. Um novo perfil de abuso de substâncias em adolescentes e jovens adultos. Acta Med Port. 2011;24:739–756.
   PubMedGoogle Scholar
• Busardò FP, Jones AW. Interpreting γ-hydroxybutyrate concentrations for clinical and forensic purposes. Clin Toxicol (Phila). 2019;57:149–163.
   PubMed Web of Science ®Google Scholar
• Fuller DE, Hornfeldt CS. From club drug to orphan drug: sodium oxybate (Xyrem) for the treatment of cataplexy. Pharmacotherapy. 2003;23:1205–1209.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Cruz V, Morris ME. γ -Hydroxybutyric Acid-Ethanol Drug-Drug Interaction: reversal of toxicity with MCT1 inhibitors. J Pharmacol Exp Ther. 2021;378:42–50.
   PubMed Web of Science ®Google Scholar
• Graeme KA. New drugs of abuse. Emerg Med Clin North Am. 2000;18:625–636.
   PubMed Web of Science ®Google Scholar
• Anderson IB, Kim SY, Dyer JE, et al. Trends in γ-hdroxybutyrate (GHB) and related drug intoxication: 1999 to 2003. Ann Emerg Med. 2006;47:177–183.
   PubMed Web of Science ®Google Scholar
• Gahlinger PM. Club drugs: MDMA, gamma-hydroxybutyrate (GHB), Rohypnol, and ketamine. Am Fam Physician. 2004;69:2619–2627.
   PubMed Web of Science ®Google Scholar
• Degenhardt L, Copeland J, Dillon P. Recent trends in the use of “club drugs”: an Australian review. Subst Use Misuse. 2005;40:1241–1256.
   PubMed Web of Science ®Google Scholar
• Jones AW, Holmgren A, Kugelberg FC, et al. Relationship between postmortem urine and blood concentrations of GHB furnishes useful information to help interpret drug intoxication deaths. J Anal Toxicol. 2018;42:587–591.
   PubMed Web of Science ®Google Scholar
• Wong CGT, Gibson KM, Snead OC. From the street to the brain: neurobiology of the recreational drug γ-hydroxybutyric acid. Trends Pharmacol Sci. 2004;25:29–34.
   PubMed Web of Science ®Google Scholar
• Busardò FP, Gottardi M, Tini A, et al. Replacing GHB with GBL in Recreational Settings: a New Trend in Chemsex. Curr Drug Metab. 2018;19:1080–1085.
   PubMed Web of Science ®Google Scholar
• Tini A, Del Rio A. Has GBL replaced GHB in recreational settings? Arh Hig Rada Toksikol. 2020;71:167–168.
   PubMed Web of Science ®Google Scholar
• Di Trana A, Beck R, Del Rio A. Management of GHB acute intoxications. Clin Ter. 2021;171:e49–e51.
   PubMedGoogle Scholar
• Marinelli E, Beck R, Malvasi A, et al. Gamma-hydroxybutyrate abuse: pharmacology and poisoning and withdrawal management. Arh Hig Rada Toksikol. 2020;71:19–26.
   PubMed Web of Science ®Google Scholar
• WHO. Gamma-butyrolactone (GBL) critical review report Agenda item 4.3 expert committee on drug dependence thirty-sixth meeting [Internet]. [cited 2021 Jul 17]. Available from: https://www.who.int/medicines/areas/quality_safety/4_3_Review.pdf
   Google Scholar
• Palmer RB. Gamma-butyrolactone and 1,4-butanediol: abused analogues of gamma-hydroxybutyrate. Toxicol Rev. 2004;23:21–31.
   PubMedGoogle Scholar
• EMCCDA. GHB and its precursor GBL: an emerging trend case study [Internet]. cited 2021 Jul 17]. Available from: https://www.emcdda.europa.eu/system/files/publications/505/TP_GHB_and_GBL_107300.pdf
   Google Scholar
• Giorgetti R, Tagliabracci A, Schifano F, et al. When “Chems” meet sex: a rising phenomenon called “ChemSex. Curr Neuropharmacol. 2017;15:762–770.
   PubMed Web of Science ®Google Scholar
• Bourne A, Reid D, Hickson F, et al. 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;91:564–568.
   PubMed Web of Science ®Google Scholar
• Bohn A, Sander D, Köhler T, et al. Chemsex and mental health of men who have sex with men in Germany. Front Psychiatry. 2020;11:542301.
   PubMedGoogle Scholar
• Barrett P, O’Donnell K, Fitzgerald M, et al. Drug use among men who have sex with men in Ireland: prevalence and associated factors from a national online survey. Int J Drug Policy. 2019;64:5–12.
   PubMed Web of Science ®Google Scholar
• Tomkins A, Vivancos R, Ward C, et al. How can those engaging in chemsex best be supported? An online survey to gain intelligence in Greater Manchester. Int J STD AIDS. 2018;29:128–134.
   PubMed Web of Science ®Google Scholar
• Whipple JK, Quebbeman EJ, Lewis KS, et al. Difficulties in diagnosing narcotic overdoses in hospitalized paitents. Ann Pharmacother. 1994;28:446–450.
   PubMed Web of Science ®Google Scholar
• Sivilotti MLA, Burns MJ, Aaron CK, et al. Pentobarbital for severe gamma-butyrolactone withdrawal. Ann Emerg Med. 2001;38:660–665.
   PubMed Web of Science ®Google Scholar
• Corkery JM, Loi B, Claridge H, et al. Deaths in the lesbian, gay, bisexual and transgender United Kingdom communities associated with GHB and precursors. Curr Drug Metab. 2018;19:1086–1099.
   PubMed Web of Science ®Google Scholar
• Tay EM, Graham RI, Day RO. Severe GHB withdrawal delirium managed with dexmedetomidine. Med J Aust. 2016;205:251–252.
   PubMed Web of Science ®Google Scholar
• Ryan JM, Stell I. Gamma hydroxybutyrate - a coma inducing recreational drug. J Accid Emerg Med. 1997;14:259–261.
   PubMedGoogle Scholar
• Boyce SH, Padgham K, Miller LD, et al. Gamma hydroxybutyric acid (GHB): an increasing trend in drug abuse. Eur J Emerg Med. 2000;7:177–181.
   PubMedGoogle Scholar
• Espinosa G, Miró Ò, Nogué S, et al. Liquid ecstasy poisoning: study of 22 cases. Med Clin (Barc). 2001;117:56–58.
   PubMed Web of Science ®Google Scholar
• Muller AA. GHB poisoning: three recent cases reflect the continuing danger. J Emerg Nurs. 2003;29:72–74.
   PubMedGoogle Scholar
• Pichini S, Marchei E, Pacifici R, et al. Chemsex intoxication involving sildenafil as an adulterant of GHB. Drug Test Anal. 2017;9:956–959.
   PubMed Web of Science ®Google Scholar
• Bosman IJ, Lusthof KJ. Forensic cases involving the use of GHB in The Netherlands. Forensic Sci Int. 2003;133:17–21.
   PubMed Web of Science ®Google Scholar
• Caldicott DGE, Chow FY, Burns BJ, et al. Fatalities associated with the use of γ-hydroxybutyrate and its analogues in Australasia. Med J Aust. 2004;181:310–313.
   PubMed Web of Science ®Google Scholar
• Kugelberg FC, Holmgren A, Eklund A, et al. Forensic toxicology findings in deaths involving gamma-hydroxybutyrate. Int J Legal Med. 2010;124:1–6.
   PubMed Web of Science ®Google Scholar
• Zvosec DL, Smith SW, Hall BJ. Three deaths associated with use of Xyrem. Sleep Med. 2009;10:490–493.
   PubMed Web of Science ®Google Scholar
• Grimsrud MM, Brekke M, Syse VL, et al. Acute poisoning related to the recreational use of prescription drugs: an observational study from Oslo, Norway. BMC Emerg Med. 2019;19:55.
   PubMed Web of Science ®Google Scholar
• Brunetti P, Giorgetti R, Tagliabracci A, et al. Designer benzodiazepines: a review of toxicology and public health risks. Pharmaceuticals (Basel). 2021;14:560.
   PubMedGoogle Scholar
• Ansseau M, Doumont A, Thiry D, et al. Initial study of methylclonazepam in generalized anxiety disorder - Evidence for greater power in the cross-over design. Psychopharmacology (Berl). 1985;87:130–135.
   PubMed Web of Science ®Google Scholar
• Lader MH. Limitations on the use of benzodiazepines in anxiety and insomnia: are they justified? Eur Neuropsychopharmacol. 1999;9(6):S399–405.
   PubMedGoogle Scholar
• Barnas C, Rossmann M, Roessler H, et al. Benzodiazepines and other psychotropic drugs abused by patients in a methadone maintenance program: familiarity and preference. Clin Neuropharmacol. 1992;12:397–402.
   Google Scholar
• Talbert JJ. Club drugs: coming to a patient near you. Nurse Pract. 2014;39:20–25; quiz 25–26.
   PubMedGoogle Scholar
• Britt GC, McCance-Katz EF. A brief overview of the clinical pharmacology of “club drugs. Subst Use Misuse. 2005;40:1189–1201.
   PubMed Web of Science ®Google Scholar
• Couper FJ, Thatcher JE, Logan BK. Suspected GHB overdoses in the emergency department. J Anal Toxicol. 2004;28:481–484.
   PubMed Web of Science ®Google Scholar
• Akins BE, Miranda E, Matthew Lacy J, et al. A multi-drug intoxication fatality involving Xyrem (GHB). J Forensic Sci. 2009;54:495–496.
   PubMed Web of Science ®Google Scholar
• Armstrong SC, Cozza KL. Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part II. Psychosomatics. 2003;44:515–520.
   PubMed Web of Science ®Google Scholar
• Inturrisi CE. Clinical pharmacology of opioids for pain. Clin J Pain. 2002;18:S3–13.
   PubMed Web of Science ®Google Scholar
• Guerzoni S, Pellesi L, Pini LA, et al. Drug-drug interactions in the treatment for alcohol use disorders: a comprehensive review. Pharmacol Res. 2018;133:65–76.
   PubMed Web of Science ®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;53:52–78.
   PubMed Web of Science ®Google Scholar
• EMA. Xyrem® (sodium oxybate) product information [Internet] Accessed17 Jul 2021. Available from: https://www.ema.europa.eu/en/documents/product-information/xyrem-epar-product-information_en.pdf
   Google Scholar
• FDA. Xyrem® (sodium oxybate) oral solution information [Internet] Accessed17 Jul 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021196s030lbl.pdf
   Google Scholar
• Weiss T, Müller D, Marti I, et al. Gamma-hydroxybutyrate (GHB) and topiramate - Clinically relevant drug interaction suggested by a case of coma and increased plasma GHB concentration. Eur J Clin Pharmacol. 2013;69:1193–1194.
   PubMed Web of Science ®Google Scholar
• Caputo F, Bernardi M. Medications acting on the GABA system in the treatment of alcoholic patients. Curr Pharm Des. 2010;16:2118–2125.
   PubMed Web of Science ®Google Scholar
• Wilens TE, Adler LA, Adams J, et al. Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry. 2008;47:21–31.
   PubMed Web of Science ®Google Scholar
• Fischer BA, Boggs DL. The role of antihistaminic effects in the misuse of quetiapine: a case report and review of the literature. Neurosci Biobehav Rev. 2010;34:555–558.
   PubMed Web of Science ®Google Scholar
• Frauger E, Amaslidou D, Spadari M, et al. Patterns of methylphenidate use and assessment of its abuse among the general population and individuals with drug dependence. Eur Addict Res. 2016;22:119–126.
   PubMed Web of Science ®Google Scholar
• Sullivan M, Evans E. Abuse and misuse of antidepressants. Subst Abuse Rehabil. 2014;5:107–120.
   PubMedGoogle Scholar
• Hasnain M, Vieweg WVR. QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review. CNS Drugs. 2014;28:887–920.
   PubMed Web of Science ®Google Scholar
• Avidan AY, Kushida CA. The sodium in sodium oxybate: is there cause for concern? Sleep Med. 2020;75:497–501.
   PubMed Web of Science ®Google Scholar
• Hoaken PNS, Stewart SH. Drugs of abuse and the elicitation of human aggressive behavior. Addict Behav. 2003;28:1533–1554.
   PubMed Web of Science ®Google Scholar
• Frati P, Busardò FP, Cipolloni L, et al. Anabolic androgenic steroid (AAS) related deaths: autoptic, histopathological and toxicological findings. Curr Neuropharmacol. 2015;13:146–159.
   PubMed Web of Science ®Google Scholar
• Petersson A, Garle M, Holmgren P, et al. Toxicological findings and manner of death in autopsied users of anabolic androgenic steroids. Drug Alcohol Depend. 2006;81:241–249.
   PubMed Web of Science ®Google Scholar
• Busardò FP, Frati P, Sanzo M, et al. The impact of nandrolone decanoate on the central nervous system. Curr Neuropharmacol. 2015;13:122–131.
   PubMed Web of Science ®Google Scholar
• Romanelli F, Smith KM. Recreational use of sildenafil by HIV-positive and -negative homosexual/bisexual males. Ann Pharmacother. 2004;38:1024–1030.
   PubMed Web of Science ®Google Scholar
• UNODC. World Drug Report 2021. Booklet 5 - COVID-19 and drugs: impact and outlook [Internet] Accessed17 Jul 2021. Available from: https://www.unodc.org/res/wdr2021/field/WDR21_Booklet_5.pdf
   Google Scholar
• EMCDDA. European drug report 2021. Trends and Developments [Internet]. Accessed17 Jul 2021. Available from: https://www.emcdda.europa.eu/system/files/publications/13838/TDAT21001ENN.pdf
   Google Scholar
• Busardò FP, Jones A. GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome. Curr Neuropharmacol. 2015;13:47–70.
   PubMed Web of Science ®Google Scholar
• Kamal RM, van Noorden MS, Wannet W, et al. Pharmacological treatment in γ-Hydroxybutyrate (GHB) and γ-Butyrolactone (GBL) Dependence: detoxification and relapse prevention. CNS Drugs. 2017 Jan;31(1):51–64.
   PubMed Web of Science ®Google Scholar
• Kintz P, Villain M, Pélissier AL, et al. Unusually high concentrations in a fatal GHB case. J Anal Toxicol. 2005;29:582–585.
   PubMed Web of Science ®Google Scholar
• Mazarr-Proo S, Kerrigan S. Distribution of GHB in tissues and fluids following a fatal overdose. J Anal Toxicol. 2005;29:398–400.
   PubMed Web of Science ®Google Scholar
• Busardò FP, Pichini S, Zaami S, et al. Hair testing of GHB: an everlasting issue in forensic toxicology. Clin Chem Lab Med. 2018;56:198–208.
   PubMed Web of Science ®Google Scholar
• UNODC. Guidelines for the forensic analysis of drugs facilitating sexual assault and other criminal acts [Internet] Accessed 17 Jul 2021. Available from: https://www.unodc.org/documents/scientific/forensic_analys_of_drugs_facilitating_sexual_assault_and_other_criminal_acts.pdf
   Google Scholar
• Bertol E, Mari F, Vaiano F, et al. Determination of GHB in human hair by HPLC-MS/MS: development and validation of a method and application to a study group and three possible single exposure cases. Drug Test Anal. 2015;7:376–384.
   PubMed Web of Science ®Google Scholar
• Busardò FP, Kyriakou C. GHB in biological specimens: which cut-off levels should be taken into consideration in forensic toxicological investigation? Recent Pat Biotechnol. 2014;8:206–214.
   PubMedGoogle Scholar
• Busardò FP, Vaiano F, Mannocchi G, et al. Twelve months monitoring of hair GHB decay following a single dose administration in a case of facilitated sexual assault. Drug Test Anal. 2017;9:953–956.
   PubMed Web of Science ®Google Scholar
• Giorgetti R, Busardò FP, Tagliabracci A. Interpreting GHB concentrations in hair: can a cut-off be established? Forensic Sci Int. 2020;306 110009. Available from
   PubMed Web of Science ®Google Scholar