title: Cannabidiol rescues acute hepatic toxicity and seizure induced by cocaine.
abstract: Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity. URB597 (1.0 mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg) reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.
authors.affiliation: Laboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil ; Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Luciano Rezende
authors.initials: LR
authors.lastname: Vilela
authors.affiliation: Laboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Lindisley Ferreira
authors.initials: LF
authors.lastname: Gomides
authors.affiliation: Laboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Bruna Araújo
authors.initials: BA
authors.lastname: David
authors.affiliation: Laboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Maísa Mota
authors.initials: MM
authors.lastname: Antunes
authors.affiliation: Laboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Ariane Barros
authors.initials: AB
authors.lastname: Diniz
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Fabrício de Araújo
authors.initials: Fde A
authors.lastname: Moreira
authors.affiliation: Laboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Gustavo Batista
authors.initials: GB
authors.lastname: Menezes
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002185:Cannabidiol / Q000627:therapeutic use*; D003042:Cocaine / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008099:Liver / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D002185:Cannabidiol; D000082:Acetaminophen; D000410:Alanine Transaminase; D003042:Cocaine