Exploring the safety of cannabidiol (CBD) : a comprehensive in vitro evaluation of the genotoxic and mutagenic potential of a CBD isolate and extract from Cannabis sativa L.

Štern, Alja (author), Novak, Matjaž (author), Kološa, Katja (author), Trontelj, Jurij (author), Žabkar, Sonja (author), Šentjurc, Tjaša (author), Filipič, Metka (author), Žegura, Bojana (author)

Cannabidiol (CBD), a naturally occurring cyclic terpenoid found in Cannabis sativa L., is renowned for its diverse pharmacological benefits. Marketed as a remedy for various health issues, CBD products are utilized by patients as a supplementary therapy or post-treatment failure, as well as by healthy individuals seeking promised advantages. Despite its widespread use, information regarding potential adverse effects, especially genotoxic properties, is limited. The present study is focused on the mutagenic and genotoxic activity of a CBD isolate (99.4 % CBD content) and CBD-rich Cannabis sativa L extract (63.6 % CBD content) in vitro. Both CBD samples were non-mutagenic, as determined by the AMES test (OECD 471) but exhibited cytotoxicity for HepG2 cells (~IC$_{50 (4 h)}$ 26 µg/ml, ~IC$_{50 (24 h)}$ 6–8 µg/ml, MTT assay). Noncytotoxic concentrations induced upregulation of genes encoding metabolic enzymes involved in CBD metabolism, and CBD oxidative as well as glucuronide metabolites were found in cell culture media, demonstrating the ability of HepG2 cells to metabolize CBD. In this study, the CBD samples were found non-genotoxic. No DNA damage was observed with the comet assay, and no influence on genomic instability was observed with the cytokinesis block micronucleus and the γH2AX and p-H3 assays. Furthermore, no changes in the expression of genes involved in genotoxic stress response were detected in the toxicogenomic analysis, after 4 and 24 h of exposure. Our comprehensive study contributes valuable insights into CBD’s safety profile, paving the way for further exploration of CBD’s therapeutic applications and potential adverse effects.

• Language: English
• Keywords: cannabidiol, CBD, metabolism, cytotoxicity, genotoxicity, mutagenicity
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 13 str.
• Numbering: Vol. 177, art. 116969
• PID: 20.500.12556/RUL-166740
• UDC: 615.9
• ISSN on article: 1950-6007
• DOI: 10.1016/j.biopha.2024.116969
• COBISS.SI-ID: 200108803
• Publication date in RUL: 23.01.2025

Record is a part of a journal

• Title: Biomedicine & pharmacotherapy
• Shortened title: Biomed. pharmacother.
• Publisher: Éditions scientifiques et médicales Elsevier
• ISSN: 1950-6007
• COBISS.SI-ID: 23136261

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.

Secondary language

• Language: Slovenian
• Keywords: kanabidol, CBD, izvleček Cannabis sativa L., varnost, genotoksičnost