Synthetic cannabinoid receptor agonists (SCRA) share minimal structural similarities to tetrahydrocannabinol or themselves. Due to their heterogeneous structures and the rapid appearance and disappearance of new SCRA on the drug scene, the quantitation of SCRA has not been attempted extensively. We present a wide series of SCRA concentrations based on a single-point calibration using peak height ratios for the extracted ion chromatogram of the protonated precursor ion against that of the internal standard. These concentrations are viewed as indicative only given the use of a single concentration “calibrator” based on the response of a deuterated analogue of a structurally related compound. What is of note, is that, despite the potential differences in potency the majority of SCRA seem to have relatively similar concentrations in postmortem cases.
MillsBYepesANugentK. Synthetic cannabinoids. Am J Med Sci. 2015;350(1):59–62.
2.
PertweeRG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol. 2006;147(S1):S163–S171.
3.
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). European Monitoring Centre for Drugs and Drug Addiction: European Drug Report 2018: Trends and Developments. EMCDDA; June2018.
4.
ØiestadELKarinenRHauglandKØiestadÅM. Screening of synthetic cannabinoids. In: PreedyVR ed., Handbook of Cannabis and Related Pathologies Biology, Pharmacology, Diagnosis, and Treatment. Academic Press; 2017:981–997. doi:10.1016/B978-0-12-800756-3.00118-6
5.
Home Office. Psychoactive Substances Act 2016: Guidance for Researchers. GOV.UK; 2016:1–63.
6.
GrabenauerMKrolWLWileyJLThomasBF. Analysis of synthetic cannabinoids using high-resolution mass spectrometry and mass defect filtering: implications for nontargeted screening of designer drugs. Anal Chem. 2012;84(13):5574–5581. doi:10.1021/ac300509 h
7.
KronstrandRRomanMAnderssonMEklundA. Toxicological findings of synthetic cannabinoids in recreational users. J Anal Toxicol. 2013;37(8):534–541.
8.
KnittelJLHollerJMChmielJD, et al.Analysis of parent synthetic cannabinoids in blood and urinary metabolites by liquid chromatography tandem mass spectrometry. J Anal Toxicol. 2016;40(3):173–186. doi:10.1093/jat/bkv137
9.
ErnstLLangerNBockelmannASalkhordehEBeuerleT. Identification and quantification of synthetic cannabinoids in ‘spice-like’ herbal mixtures: update of the German situation in summer 2018. Forensic Sci Int. 2019;294:96–102. doi:10.1016/j.forsciint.2018.11.001
10.
TeskeJWellerJPFieguthARothämelTSchulzYTrögerHD. Sensitive and rapid quantification of the cannabinoid receptor agonist naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in human serum by liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci. 2010;878(27):2659–2663. doi:10.1016/j.jchromb.2010.03.016
11.
KacinkoSLXuAHomanJWMcMullinMMWarringtonDMLoganBK. Development and validation of a liquid chromatography-tandem mass spectrometry method for the identification and quantification of JWH-018, JWH-073, JWH-019, and JWH-250 in human whole blood. J Anal Toxicol. 2011;35(7):386–393.
12.
HasegawaKWuritaAMinakataK, et al.Identification and quantitation of 5-fluoro-ADB, one of the most dangerous synthetic cannabinoids, in the stomach contents and solid tissues of a human cadaver and in some herbal products. Forensic Toxicol. 2015;33(1):112–121. doi:10.1007/s11419-014-0259-0
13.
HasegawaKWuritaAMinakataK, et al.Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms. Forensic Toxicol. 2015;33(1):45–53. doi:10.1007/s11419-014-0245-6
14.
AdamowiczPMeissnerEMaślankaM. Fatal intoxication with new synthetic cannabinoids AMB-FUBINACA and EMB-FUBINACA. Clin Toxicol. 2019;57(11):1103–1108.
15.
SharpPHudsonSHikinLSmithPRMorleySR. The changing pattern of synthetic cannabinoid use within England, April 2014 to March 2018. Med Sci Law. 2019;59(3):180–186.
SchaeferNKröllAKKörbelC, et al.Time- and temperature-dependent postmortem concentration changes of the (synthetic) cannabinoids JWH-210, RCS-4, as well as Δ9-tetrahydrocannabinol following pulmonary administration to pigs. Arch Toxicol. 2020;94(5):1585. doi:10.1007/s00204-020-02707-4
18.
SchaeferNKröllAKKörbelC, et al.Distribution of the (synthetic) cannabinoids JWH-210, RCS-4, as well as Δ9-tetrahydrocannabinol following pulmonary administration to pigs. Arch Toxicol. 2019;93(8):2211–2218. doi:10.1007/s00204-019-02493-8
19.
BolandDMReidyLJSeitherJMRadtkeJMLewEO. Forty-three fatalities involving the synthetic cannabinoid, 5-fluoro-ADB: forensic pathology and toxicology implications. J Forensic Sci. 2020;65(1):170–182.
20.
ElmoreJSBaumannMH. Repeated exposure to the spice cannabinoid JWH-018 induces tolerance and enhances responsiveness to 5-HT1A receptor stimulation in male rats. Front Psychiatry. 2018;9:55. doi:10.3389/fpsyt.2018.00055
21.
TaiSHyattWSGuC, et al.Repeated administration of phytocannabinoid Δ9-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner. Pharmacol Res. 2015;102:22–23. doi:10.1016/j.phrs.2015.09.006
22.
SaitoTNameraAMiuraN, et al.A fatal case of MAM-2201 poisoning. Forensic Toxicol. 2013;31(2):333–337. doi:10.1007/s11419-013-0190-9
23.
SasakiCSaitoTShinozukaT, et al.A case of death caused by abuse of a synthetic cannabinoid N-1-naphthalenyl-1-pentyl-1H-indole-3-carboxamide. Forensic Toxicol. 2015;33(1):165–169. doi:10.1007/s11419-014-0246-5
24.
GiorgettiABusardòFPTittarelliRAuwärterVGiorgettiR. Post-mortem toxicology: a systematic review of death cases involving synthetic cannabinoid receptor agonists. Front Psychiatry. 2020;11:464. doi:10.3389/fpsyt.2020.00464
25.
AdamsAJBanisterSDIrizarryLTreckiJSchwartzMGeronaR. Zombie outbreak caused by the synthetic cannabinoid AMB-FUBINACA in New York. N Engl J Med. 2017;376(3):235–242. doi:10.1056/NEJMoa1610300
26.
ThomsenRNielsenLMHolmNBRasmussenHBLinnetK; INDICES Consortium. Synthetic cannabimimetic agents metabolized by carboxylesterases. Drug Test Anal. 2015;7(7):565–576. doi:10.1002/dta.1731
27.
VikingssonSGréenHBrinkhagenLMukhtarSJosefssonM. Identification of AB-FUBINACA metabolites in authentic urine samples suitable as urinary markers of drug intake using liquid chromatography quadrupole tandem time of flight mass spectrometry. Drug Test Anal. 2016;8(9):950–956. doi:10.1002/dta.1896
28.
Hsin-Hung ChenMDipAAhmedM, et al.Detection and characterization of the effect of AB-FUBINACA and its metabolites in a rat model. J Cell Biochem. 2016;117(4):1033–1043. doi:10.1002/jcb.25421
29.
CastanetoMSWohlfarthAPangS, et al.Identification of AB-FUBINACA metabolites in human hepatocytes and urine using high-resolution mass spectrometry. Forensic Toxicol. 2015;33(2):295–310. doi:10.1007/s11419-015-0275-8
30.
TruverMTWatanabeSÅstrandA, et al.5F-MDMB-PICA metabolite identification and cannabinoid receptor activity. Drug Test Anal. 2020;12(1):127–135. doi:10.1002/dta.2688
31.
SherpaDPaudelBMSubediBHChowRD. Synthetic cannabinoids: the multi-organ failure and metabolic derangements associated with getting high. J. Community Hosp Intern Med Perspect. 2015;5(4):27540. doi:10.3402/jchimp.v5.27540
32.
HessCStockhausenSKernbach-WightonGMadeaB. Death due to diabetic ketoacidosis: induction by the consumption of synthetic cannabinoids?Forensic Sci Int. 2015;257:e6–e11. doi:10.1016/j.forsciint.2015.08.012
33.
NagappanAShinJJungMH. Role of cannabinoid receptor type 1 in insulin resistance and its biological implications. Int J Mol Sci. 2019;20(9):2109. doi:10.3390/ijms20092109
34.
KrotulskiAJMohrALKacinkoSL, et al.4F-MDMB-BINACA: a new synthetic cannabinoid widely implicated in forensic casework. J Forensic Sci. 2019;64(5):1451–1461. doi:10.1111/1556-4029.14101
35.
WatanabeSVikingssonSÅstrandAGréenHKronstrandR.Biotransformation of the new synthetic cannabinoid with an alkene, MDMB-4en-PINACA, by human hepatocytes, human liver microsomes, and human urine and blood. AAPS J. 2020;22(1):1–9. doi:10.1208/s12248-019-0381-3
36.
SeywrightATorranceHJWylieFMMcKeownDALoweDJStevensonR. Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA. Clin Toxicol. 2016;54(8):632–637. doi:10.1080/15563650.2016.1186805
37.
ShanksKGBehonickGS. Death after use of the synthetic cannabinoid 5F-AMB. Forensic Sci Int. 2016;262:e21–e24.
38.
ShanksKGClarkWBehonickG. Death associated with the use of the synthetic cannabinoid ADB-FUBINACA. J Anal Toxicol. 2016;40(3):236–239. doi:10.1093/jat/bkv142
39.
MaedaHKikura-HanajiriRKawamuraMNagashimaEYoshidaKI. AB-CHMINACA-induced sudden death from non-cardiogenic pulmonary edema. Clin Toxicol. 2018;56(2):143–145. doi:10.1080/15563650.2017.1340648
40.
SchwartzMDTreckiJEdisonLASteckARArnoldJKGeronaRR. A common source outbreak of severe delirium associated with exposure to the novel synthetic cannabinoid ADB-PINACA. J Emerg Med. 2015;48(5):573–580. doi:10.1016/j.jemermed.2014.12.038
