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Article 2024 · 3 citations

A study on the possible neurotoxic effects of CUMYL-4CN-BINACA in Sprague Dawley rats

Lafzi, Ayse, Demirci, Tuba, Yuce, Neslihan, Annac, Ebru, Cicek, Mustafa, Sisman, Turgay

Abstract

Substances such as Delta 9-tetrahydrocannabinol (THC) and cannabidiol cross the blood-brain barrier. Detecting the damage of these substances in the brain provides important data in drug abuse studies. The aim of the study is to define the neurotoxicity of a novel synthetic cannabinoid (CUMYL-4CN-BINACA) in the Sprague-Dawley rats. Histopathological, immunohistochemical, behavioral, and biochemical examinations were performed to determine the acute and subacute toxicity of the cannabinoid. Three cannabinoid doses were administered for 2 days in the acute exposure groups and 14 days in the subacute exposure groups. Observations were made for 14 days and various changes such as mortality, injury, and illness were recorded daily. No mortality was determined. Serious pathological changes such as neurodegeneration, focal plague formation, vacuolation, edema, congestion, and fibrosis were observed in the cerebral cortex and hippocampus of the brain in a dose-dependent manner. Brain tissue caspase-3 activity showed that the cannabinoid triggered apoptosis in the rat brain. The detected cellular oxidative stress (higher lipid peroxidation and lower antioxidant enzyme activity) also supported neurotoxicity. Significant behavioral abnormalities were also observed in the acute groups, while no behavioral changes were detected in the subacute groups. This study showed for the first time that CUMYL-4CNBINACA adversely affects the rat brain. It can be estimated that the abuse of the cannabinoid may harm human health in the same way.

Keywords
CUMYL-4CN-BINACA Preclinical profile Brain histology Behavioral analysis Oxidative stress Apoptosis CANNABINOIDS CUMYL-PINACA SYNTHETIC CANNABINOIDS LOCOMOTOR-ACTIVITY IN-VITRO DOWN-REGULATION CB1 RECEPTOR PHARMACOLOGY APOPTOSIS TOXICITY MICE
WoS Categories
Medicine, Legal Social Sciences, Biomedical
Sustainable Development Goals
Citation
Journal
LEGAL MEDICINE
Year
2024
Volume
67
ISSN
1344-6223
DOI
10.1016/j.legalmed.2023.102389
WoS UID
WOS:001155101700001
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