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Human Toxicity Caused by Indole and Indazole Carboxylate Synthetic Cannabinoid Receptor Agonists: From Horizon Scanning to Notification

Lookup NU author(s): Dr Simon Hill, Dr Michael Dunn, Dr Celine Cano, Dr Suzannah Harnor, Dr Ian Hardcastle, Professor Simon Thomas

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Association for Clinical Chemistry, 2018.

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Abstract

Background. The emergence of Novel Psychoactive Substances (NPS), particularly Synthetic Cannabinoid Receptor Agonists (SCRA), has involved hundreds of potentially harmful chemicals in a highly dynamic international market challenging users’, clinicians’ and regulators’ understanding of what circulating substances are causing harm. We describe a toxicovigilance system for NPS that predicted the UK emergence and identified the clinical toxicity caused by novel indole and indazole carboxylate SCRA.Methods. To assist early accurate identification, we synthesised 5 examples of commercially-unavailable indole and indazole carboxylate SCRA (FUB-NPB-22, 5F-NPB-22, 5F-SDB-005, FUB-PB-22, NM-2201). We analysed plasma and urine samples from 160 patients presenting to emergency departments with severe toxicity after suspected NPS use during 2015-2016 for these and other NPS using data-independent liquid chromatography–tandem mass spectrometry. Results. We successfully synthesised five carboxylate SCRA, using established synthetic and analytical chemistry methodologies. We identified at least one SCRA in samples from 49 patients, including an indole or indazole carboxylate SCRA in 17 (35%), specifically 5F-PB-22 (14%), FUB PB-22 (6%), BB-22 (2%), 5F NPB-22 (20%), FUB NPB-22 (2%), and 5F-SDB-005 (4%). In these 17 patients, there was analytical evidence of other substances in 16. Clinical features included agitation / aggression (82%), reduced consciousness (76%), acidosis (47%), hallucinations / paranoid features (41%), tachycardia (35%), hypertension (29%), raised creatine kinase (24%) and seizures (12%).Conclusions. This toxicovigilance system predicted the emergence of misuse of indole and indazole carboxylate SCRA, documented associated clinical harms, and notified relevant agencies. Toxicity appears consistent with other SCRA, including mental state disturbances and reduced consciousness.


Publication metadata

Author(s): Hill SL, Dunn M, Cano C, Harnor SJ, Hardcastle IR, Grundlingh J, Dargan PI, Wood DM, Tucker S, Bartram T, Thomas SHL

Publication type: Article

Publication status: Published

Journal: Clinical Chemistry

Year: 2018

Volume: 64

Issue: 2

Pages: 346-354

Print publication date: 01/02/2018

Online publication date: 01/02/2018

Acceptance date: 19/09/2017

Date deposited: 28/09/2017

ISSN (print): 0009-9147

ISSN (electronic): 1530-8561

Publisher: American Association for Clinical Chemistry

URL: https://doi.org/10.1373/clinchem.2017.275867

DOI: 10.1373/clinchem.2017.275867


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