In vitro cannabinoid receptor activity, metabolism, and detection in seized samples of CH-PIATA, a new indole-3-acetamide synthetic cannabinoid

The rapidly evolving synthetic cannabinoid receptor agonist (SCRA) market poses significant challenges for forensic scientists. Since the enactment of a generic ban in China, a variety of new drugs have emerged capable of evading the legislation by carrying new structural features. One recent example of a SCRA with new linker and head moieties is CH-PIATA (CH-PIACA, CHX-PIATA, and CHX-PIACA). CH-PIATA bears an additional methylene spacer in the linker moiety between the indole core and the traditional carbonyl component of the linker. CH-PIATA was detected once in a seized powder by Belgian customs and 12 times in Scottish prisons in infused papers or resin. The metabolites of CH-PIATA were investigated via in vitro human liver microsome (HLM) incubations and eight metabolites were identified, dominated by oxidative biotransformations. A blood sample was confirmed to contain a mixture of SCRAs including CH-PIATA via presence of the parent and at least five of the metabolites identified from HLM incubations. Furthermore, this paper evaluates the intrinsic in vitro cannabinoid 1 and 2 receptor (CB1 and CB2) activation potential of CH-PIATA reference material and the powder seized by Belgian customs by means of β-arrestin 2 (βarr2) recruitment assays. Both the reference and the seized powder showed a weak activity at both CB receptors with signs of antagonism found. Based on these results, the expected harm potential of this newly emerging substance remains limited.

NORMAN Caitlyn;  DEVENTER Marie;  DREMANN Olivia;  REID Robert;  VAN UYTFANGHE Katleen;  GUILLOU Claude;  VINCKIER Inge;  NIC DAÉID Niamh;  KROTULSKI Alex;  STOVE Christophe; 

2024-11-27

WILEY

JRC132807

1942-7603 (online),   

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/dta.3555,    https://publications.jrc.ec.europa.eu/repository/handle/JRC132807,   

10.1002/dta.3555 (print),