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Objective: The present study examined the in vitro effects on oral squamous cell carcinoma cells (HSC-3) of cannabidiol (CBD), the main chemical component of Cannabis, proposed as a novel adjuvant therapy in the treatment of cancers., Design: Cell viability (MTT assay), morphology (SEM), apoptosis and cell cycle (flow cytometry), and DNA damage (phospho-γ-H2AX immunofluorescence) were evaluated. Cytotoxicity was evaluated with concentrations between 100 µM and 1 µM, and two concentrations were selected for subsequent analysis: 25 µM, as toxic dose, and 6.25 µM, as non-toxic., Results: CBD caused a dose- and time-dependent reduction in viability of 64 %, 96 %, and 99 % with 25 µM, 50 µM and 100 µM, respectively, after 72 h (p < 0.001), cell cycle arrest in G0-G1 phase with increased apoptosis in particular at 72 h for 25 µM (p < 0.001), significant morphological alterations with 25 µM, still present even at 6.25 µM, and significantly increased cell damage considering a significant increase in the percentage of highly positive cells (5 phosphorylated γH2AX foci), which is around 29 % for 25 µM and 19 % for 6.25 µM after 24 h., Conclusions: CBD inhibits oral cancer growth causing DNA damage. In general, induced cell cytotoxicity appears to be dose- and time-related. Doses of CBD ≥25 μM showed a high reduction in viability. CBD could possibly represent a new therapeutic molecule for its cytotoxic effects against oral squamous cell carcinoma. The mechanism involved in the suppressive effect caused by CBD needs further investigation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cannabidiol is gaining increasing interest for its potential anti-inflammatory, immunomodulatory, and antineoplastic effects. The purpose of this study is to investigate the biological effects of acute and chronic CBD administration on gingival fibroblasts and oral keratinocytes. Viability, morphology, migration, apoptosis and cell cycle, and expression of related genes (p53, BCL2, p21, and BAX) and of endocannabinoid system receptors (CB1, CB2 and GPR55) with real-time PCR and DNA damage with phospho-γ-H2AX immunofluorescence detection were analyzed. Concentrations between 100 μM and 0.001 μM were used: 50 μM (toxic dose), 25 μM (viability promoter), and 1 μM (nontoxic), were selected for subsequent chronic analysis. Acute treatment reveals significant effects than chronic, in particular in fibroblasts: concentrations ≥50 μM are highly cytotoxic, with increased apoptosis and reduced migration. Cell death correlates with increased p53 and BAX, followed by arrest in G0/G1 phase, with elevated p21 levels, suggesting a time- and dose-dependent damage. An increase in H2AX phosphorylation was observed with 25 μM and 50 μM, while 1 μM was biocompatible. Keratinocytes showed less cytotoxic effect than fibroblasts. Induced cell damage was dose- and time-related, with less damage after chronic treatment. Further investigations are needed with longer time frames to evaluate CBD dose- and time-dependent effects to identify an effective therapeutic dose., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This systematic review examine the biological effects of CBD, a major component of therapeutic Cannabis, on human pathological and cancer cell populations of integumentary, gastro-intestinal, genital and breast, respiratory, nervous, haematopoietic and skeletal districts in terms of cell viability, proliferation, migration, apoptosis, inflammation, metastasis, and CBD receptor expression. The included studies were in English, on human cell lines and primary culture from non-healthy donors with CBD exposure as variable and no CBD exposure as control. Quality assessment was based on ToxRtool with a reliability score ranging from 15 to 18. Following the PRISMA statement 4 independent reviewers performed an electronic search using MEDLINE via PubMed, Scopus and Web of Science. From 3974 articles, 83 studies have been selected. Data showed conflicting results due to different concentration exposure, administrations and time points. CBD inhibited cell viability and proliferation in most cellular districts except the integumentary apparatus. Also a significant inhibition of migration was observed in all cell types, while an increase in apoptosis at both high and low doses (greater and less than 10 μM respectively). Considering inflammation, CBD caused an anti-inflammatory effect on nervous cells at low doses and on gastro-intestinal cells at high doses, while metastatic power was reduced even at low doses, but in a skeletal cell line there was an increased angiogenesis. CB1 receptor has been related to viability effects, CB2 to apoptosis and TRPV1 to inflammation and invasiveness. A detailed insight into these aspects would allow therapeutic use of this substance without possible side effects., (Copyright © 2022 Elsevier Ltd. All rights reserved.)