Table 4.
Summary of the drug–drug interactions of CBD with anthracyclines.
| Anthracyclines | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| CT | Aim | Model | Administration | CBD c | CT c | Evaluation Time | Special Condition | Results of Combined Treatment | References |
| DOX | Cardiomyopathy | Male Sprague-Dawley rats | IP | 5 mg/kg/day for 4 weeks | 2.5 mg/kg 6x every 48 h for 2 weeks | 4 weeks + 1 day | Attenuation of cardiomyopathy | Fouad et al. (2013) [110] | |
| Cardiomyopathy | Male C57BL/6J mice | IP | 10 mg/kg 1.5 h before DOX and daily | 20 mg/kg | 5 days | Attenuation of cardiomyopathy | Hao et al. (2015) [109] | ||
| Drug accumulation | Caco-2 cells | 1, 3, 10, 30 µM | 1 µM | 1 h | Increased drug accumulation | Zhu et al. (2006) [26] | |||
| Drug accumulation | LLC-PK1 and LLC-PK1/MDR1 | 5, 20, 100 µM | 1 µM | 1 h | Increased drug accumulation | ||||
| Viability | U87MG, MZC, NHA | 10 µM | 10–5–10–3 M | 24, 72 h | Increased toxicity except for NHA | Nabissi et al. (2013) [49] | |||
| Colony formation | U87MG, MZC | 10 µM | 200 µM | 14 days | Decreased colony formation | ||||
| Apoptosis | U87MG, MZC | 10 µM | 200 µM | 6 h | Increased annexin | ||||
| DOX uptake | MZC | 10 µM 30 min before DOX | 5 µM | 0.5 + 2 h | TRPV2 dependent | ||||
| TRPV2 function | U87MG, MZC | 10 µM | 200 µM | 1 day | TRPV2 dependent | ||||
| TRPV2 function | Murine BNL1 ME A.7R.1 cells | 10 µM co- treatment and after DOX washout | 1 µM | Seconds | TRPV2 dependent | Neumann-Raizel et al. (2019) [111] | |||
| p-gp inhibition, viability, colony formation | Murine BNL1 ME A.7R.1 cells | 10 µM | 0.1 µM | 24 h | Increased toxicity | ||||
| DOX uptake | SUM159 and MDA-MB231 | 5 µM 2 h before DOX | 5 µM | 2 + 0.5 h | Higher DOX uptake | Elbaz et al. (2018) [112] | |||
| Viability | SUM159 and MDA-MB232 | 5 µM | 0.025–64 µM | 24 h | Increased toxicity | ||||
| Apoptosis | SUM159 | 5 µM | 0.5 µM | 24 h | Increased apoptosis | ||||
| Colony formation | SUM159 and MDA-MB232 | 5 µM | 0.5 µM | 6 days | Reduced serum | Decreased colony formation | |||
| Tumour growth/apoptosis | Female NU/NU nude mice with SUM159 xenograft | PT CBD; IP DOX | 5 mg/kg once per week 2 h before DOX | 5 mg/kg | 4 weeks | Lower tumour volume, increased pro-apoptotic markers | |||
| Viability | Ishikawa | 3.92 µg/ml | 0.015 and 0.03 µg/ml | 72 h | Increased toxicity | Marinelli et al. (2020) [69] | |||
| Viability, pre-administration strategy | MCF-7, MDA-MB-231 | 2.5, 5 and 10 µM (MCF-7); 1.25, 2.5 and 5 µM (MDA-MB-231) 24 h before DOX | 0.1–20 µM | 24 + 48 h | Increased toxicity (more in MDA-MB-231) | Fraguas-Sánches et al. (2020) [94] | |||
| Viability, co-treatment strategy | MCF-7, MDA-MB-231 | 10, 15 and 20 µM (MCF-7); 5, 7.5 and 10 µM (MDA-MB-231) | 0.1–20 µM | 48 h | Increased toxicity (except 10 µM CBD in MCF7) | ||||
| Viability, combination studies | MCF-7, MDA-MB-231 | CBD in solution 5 or 10 µM daily; CBD-Mps (single administration), started 24 h before DOX | 0.1–20 µM | 24 + 48 h | Increased toxicity with both formulations | ||||
| Viability, pre-administration study | SKOV-3 | 1 and 10 µM for 24 h before DOX | 1–60 µM | 24 + 48 h | Not statistically significant | Fraguas-Sánches et al. (2020) [70] | |||
| Viability, coadministration study | SKOV-3 | 10, 15, and 20 µM | 1–120 µM | 48 h | Not statistically significant | ||||
| Viability, pre- and coadministration study | SKOV-3 | CBD in solution 10 µM daily; CBD-Mps (single administration), started 24 h before DOX | 0.1–20 µM | 24 + 48 h | Increased toxicity | ||||
| Viability | MDA-MB-231 | CBD and CBD EV 1 µM (24 h before DOX) | 0.156–10 µM | 24 + 48 h | Increased sensitivity | Patel et al. (2021) [113] | |||
| Cell cycle, apoptosis, inflammatory, and metastatic markers | MDA-MB-231 | CBD and CBD EV 1 µM (24 h before DOX) | 500 nM | 24 + 48 h | Increased G1 and apoptosis, decreased inflammation and metastasis | ||||
| Cell migration | MDA-MB-231 | CBD EV 1 µM | 500 nM | 40 h (reading every 10 min) | Decreased migration | ||||
| Tumour volume, apoptosis, inflammatory and metastatic markers | Envigo nude mice (MDA-MB-231) | IP (CBD and CBD EV), IV (DOX) | CBD, CBD EV 5 mg/kg (1 day before DOX; twice weekly) | 2 mg/kg (twice weekly) | Days 1, 4, 10, and 14 | Lower tumour volume, increased apoptosis, decreased inflammation, and metastasis | |||
| Viability and synergy study | MCF7 | CBD:DOX (1:9, 2:8, 3:7, 4:6, 5:5, 6:4, 7:3, 8:2, and 9:1, v/v) |
72 h | Found the most synergistic ration | Alsherbiny et al. (2021) [95] | ||||
| Apoptosis, necrosis | MCF7 | 38, 42 µM | 0.2 µM | 24 h | Increased apoptosis and necrosis | ||||
| Viability | Canine neoplastic cell lines | 0.34, 0.67, 1.25, 2.5, 5, 10, 20 g/ml | 0.033–2 µM | 48 h | Reduced cell proliferation | Henry et al. (2021) [103] | |||
| Viability, combinatorial effect | MDA-MB-231, MDA-MB-468 | 1, 2.5 (2D); 5 (3D) µM | 0.39–25 µM (2D); 5–100 µM (3D) | 24 + 48h; 48h | Increased toxicity | Surapaneni et al. (2022) [114] | |||
| Cell migration | MDA-MB-231 | 1 µM | 500 nM | 40 h (reading every 10 min) | Anti-migratory effect | ||||
| Immunoblotting | MDA-MB-468 | 1 µM | 1 µM | 24 + 48 h | Increased cell sensitivity against DOX | ||||
c: concentration; CBD: cannabidiol; CT: chemotherapeutics; D: dimensional; DOX: doxorubicin; EV: extracellular vesicles; IP: intraperitoneal; IV: intravenous; Mps: microparticles; NHA: normal human astrocytes; PT: peritumoural.