Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol

Abstract

Cannabis sativa L., used for millennia for medicinal and industrial purposes, has a complex chemical composition, with particular emphasis on phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC). Despite advances in pharmacological research, gaps remain regarding the toxicity of full-spectrum extracts, which are essential to support their safe therapeutic use. This study aimed to evaluate the in silico toxicity of isolated Δ9-THC and CBD, as well as the acute toxicological profile of a full-spectrum extract enriched with Δ9-THC and CBD, identifying potential toxicity targets and contributing to a better understanding of their safety. For the in silico assessment, three computational tools were employed: ADMETsar, PASS online, and ProTox. The in silico results indicated acute oral toxicity classes III and IV for the chemical structures of Δ9-tetrahydrocannabinol and cannabidiol, respectively, according to the ADMETsar and ProTox analyses. Additionally, several toxicity endpoints were predicted, including respiratory toxicity, immunotoxicity, and ecotoxicity, among others. An acute oral toxicity test was conducted in an animal model following the OECD Guideline 423 (2001), using a single administration of 2000 mg/kg with a 14-day observation period. Pharmacological screening was performed, and parameters were monitored throughout the 14 days. After euthanasia, blood samples were collected for hematological and biochemical analyses. Macroscopic necropsy and histopathological examinations were also carried out. Regarding acute toxicity, no alterations were observed in hematological and histopathological parameters. The results demonstrate a favorable safety profile for the full-spectrum Cannabis sativa extract enriched with Δ9-THC and CBD, supporting its potential for controlled therapeutic applications. This research provides a scientific basis for the regulation of cannabis-based products in Brazil, contributing to clinical and regulatory decisionmaking by ANVISA.