Linking in vitro and ex vivo CB1 activity with serum concentrations and clinical features in 5F-MDMB-PICA users to better understand SCRAs and their metabolites.
Arch Toxicol
; 96(11): 2935-2945, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-35962200
ABSTRACT
Synthetic cannabinoid receptor agonists (SCRAs) pose a danger to public health. This study focused on individuals experiencing recreational drug toxicity who had used 5F-MDMB-PICA.Patient records were evaluated regarding vital signs, Glasgow Coma Scale (GCS) and clinical features. Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) confirmed and quantified the presence of 5F-MDMB-PICA (and/or metabolites) as the only SCRA present in the serum of 71 patients. Cannabinoid activity was evaluated by a cannabinoid receptor (CB1) bioassay, to assess the relationship between serum concentrations and ex vivo human CB1 activation potential. Furthermore, a link with the clinical presentation was appraised.5F-MDMB-PICA and five metabolites were pharmacologically profiled in vitro, revealing theoretically possible contributions of two active in vivo metabolites to overall cannabinoid activity. Serum concentrations of 5F-MDMB-PICA were correlated to the ex vivo cannabinoid activity, revealing a sigmoidal relationship. The latter could also be predicted based on pharmacological characterization of 5F-MDMB-PICA and its metabolites and an in-depth investigation of the bioassay outcome. Clinically, the GCS showed a significant trend (decrease) with increasing ex vivo cannabinoid activity.This is the first study to evaluate possible toxic effects of 5F-MDMB-PICA in a unique large patient cohort. It allows a better understanding of 5F-MDMB-PICA and metabolites in humans, suggesting a negligible contribution by 5F-MDMB-PICA metabolites to the overall cannabinoid activity in serum. Additionally, this work shows that in vitro pharmacological characterization allows close prediction of an individual's ex vivo CB1 activity, the latter showing a relationship with the level of consciousness.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canabinoides
/
Drogas Ilícitas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article