Cannabidiol rescues acute hepatic toxicity and seizure induced by cocaine.

Luciano Rezende Vilela,Fabrício De Araújo Moreira,Maísa Mota Antunes,Gustavo Batista Menezes,Bruna Araújo David,Ariane Barros Diniz,Lindisley Ferreira Gomides

doi:10.1155/2015/523418

Luciano Rezende Vilela, Fabrício De Araújo Moreira + Show 5 more

Open Access

https://doi.org/10.1155/2015/523418

Copy DOI

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.

Highlights

Drug abuse and addiction constitute a public health problem of great importance with a high prevalence worldwide
To investigate the hepatotoxic effects of acute cocaine intake, mice received a single administration of cocaine (75 mg/Kg; i.p.) and livers were imaged under confocal intravital microscopy
We have previously shown that hepatocytes released DNA into the liver, leading to a widespread hepatic DNA accumulation, which was directly correlated with injury severity and progression

Summary

Introduction

Drug abuse and addiction constitute a public health problem of great importance with a high prevalence worldwide. The estimated number of cocaine users globally ranges between 14 and 21 million (0.3–0.5% of the population aged between 15 and 64 years) [1]. Besides its toxicity for the cardiovascular central nervous systems, cocaine causes liver injury in human and animal models [2, 3]. This drug may lead to severe acute hepatotoxicity due to hepatocellular necrosis, which can be life threatening. As diminished liver function contributes to various adverse health effects, hepatotoxicity has been linked to the mortality in cocaine abusers [4]

Methods

Results

Conclusion