Table 2.
Summary of the drug–drug interactions of CBD with alkylating agents and platinum-based drugs.
| Alkylating Agents and Platinum-Based Drugs | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| CT | Aim | Model | Administration | CBD c | CT c | Evaluation Time | Special Condition | Results of Combined Treatment | References |
| BCNU | Viability | U87MG, MZC, NHA | 10 µM | 10−5–10−3 M/200 µM | 24, 72 h | Increased toxicity, except for NHA | Nabissi et al. (2013) [49] | ||
| Colony formation | U87MG, MZC | 10 µM | 200 µM | Day 14 | Decreased colony formation | ||||
| Apoptosis | U87MG, MZC | 10 µM | 200 µM | 6 h | Increased annexin | ||||
| TRPV2 function | U87MG, MZC | 10 µM | 200 µM | Day 1 | TRPV2 dependent | ||||
| Cell viability, differentiation, apoptosis, mitochondrial activity | GCS lines of patients with cancer | 10 µM | 200 µM | 24 h | Medium + EGF and bFGF | Restoration of BCNU sensitivity | Nabissi et al. (2015) [52] | ||
| Proliferation, viability | GBM (Hu, Ms), Ms NPCL | 0.3–100 µM | 3 µM to 1 mM | 72 h | Concentration-dependent effect | Deng et al. (2017) [53] | |||
| TMZ | Viability | U87MG, MZC, NHA | 10 µM | 10−5–10−2 M/400 µM | 24, 72 h | Increased toxicity except for NHA | Nabissi et al. (2013) [49] | ||
| Colony formation | U87MG, MZC | 10 µM | 400 µM | Day 14 | Decreased colony formation | ||||
| Apoptosis | U87MG, MZC | 10 µM | 400 µM | 6 h | Increased annexin | ||||
| TRPV2 function | U87MG, MZC | 10 µM | 400 µM | Day 1 | TRPV2 dependent | ||||
| EV release, miRs, prohibitin | LN18, LN229 | 5 µM | 800 µM | 1 h | Anti-oncogenic effect | Kosgodage et al. (2019) [58] | |||
| Proliferation and viability (effect of CBD up to BCNU toxicity) | GBM (Hu, Ms) + Ms NPCL | 0.3–100 µM | 1 µM to 1 mM | 72 h | Concentration-dependent effect | Deng et al. (2017) [53] | |||
| Survival | Patients with brain cancer | Capsule (CBD) | 100 mg twice daily, increased up to 200 mg twice daily | Standard therapy | Surgical resection + radiotherapy | Prolonged life | Likar et al. (2019) [61] | ||
| Tumour volume | Nude mice with U87 MG | Oral (CBD), IP (TMZ) | 15 mg/kg/day | 5 mg/kg/day | Day 15 | Increased tumour growth | López-Valero et al. (2018) [59] | ||
| Viability | Patient-derived GBM cells and four Glioma cell lines (U251, U87 MG, LN18) |
10, 20, 30 µM | 200, 500 µM | 48 h | Synergic effect | Huang et al. (2021) [60] | |||
| Growth inhibition | U251, LN18, and GL261 sphere culture | 30 µM | 200 µM | 24, 48 h | Synergic effect | ||||
| Colony formation assay | U251, U87 MG | 20 µM | 500 µM | Day 7 | Synergic effect | ||||
| Autophagy markers, mitophagy induction (U251) | U251, U87 MG | 30 µM | 500 µM | 24, 48 h | Increased autophagy and mitophagy | ||||
| Tumour growth, survival, markers of autophagy, mitophagy, and proliferation | Nude mice with U87 MG-GFP-luc | IP | 15 mg/kg/once daily | 25 mg/kg/once daily | Days 7, 14, 21, and 28 | Decreased tumour growth | |||
| CDDP | Renal function | Male C57BL/6J mice | IP | (2.5, 5), 10 mg/kg 1.5 before (or 12 h after) CDDP, daily | 20 mg/kg single administration | 72 (+ 1.5) h | Decreased renal toxicity | Pan et al. (2009) [64] | |
| Histopathological damage, ROS production, apoptosis, inflammation response, nitrosative stress | Male C57BL/6J mice | IP | 10 mg/kg/day 1.5 h before CDDP | 20 mg/kg single administration | 72 (+ 1.5) h | Decreased renal toxicity | |||
| CDDP-induced vomiting | Shrews | IP | 5 (attenuation), 40 (potentiation) mg/kg 0.5 h before CDDP treatment | 20 mg/kg | 1 h observation | Mealworms 15 min before pre-treatment | Modulation according to the concentration of CBD | Kwiatkowska et al. (2004) [65] | |
| CDDP-induced vomiting | Shrews | SC (CBD), IP (CDDP) | 5, 10 mg/kg 30 min before CDDP |
20, (40) mg/kg | 1 h observation | Mealworms 15 min before pre-treatment | Anti-emetic and anti-nausea effect | Rock et al. (2012) [66] | |
| CDDP-induced vomiting | Shrews | IP | CBCA: 0.5 mg/kg 45 min before CDDP | 20 mg/kg | 70 min observation | mealworms 15 min before pre-treatment | Attenuation of vomiting | Bolognini et al. (2013) [68] | |
| Viability | Ishikawa | 3.92 µg/ml | 0.25, 0.5 µg/ml | 72 h | Increased CDDP toxicity | Marinelli et al. (2020) [69] | |||
| Viability | SKOV-3 | 1, 10 µM pre-treatment for 24 h; 10, 15, 20 µM co-treatment | 5–100 µM | (24 +) 48 h | No effect (or antagonistic effect) | Fraguas-Sánchez et al. (2020) [70] | |||
| Proliferation, viability | GBM (Hu, Ms) + Ms NPCL | 0.3–100 µM | 0.1–100 µM | 72 h | Concentration-dependent effect | Deng et al. (2017) [53] | |||
| L-OHP | Mechanical allodynia | Male C57Bl6 mice | IP | 1.25–10 mg/kg 15 min before L-OHP | 6 mg/kg single administration | Days 2, 4, 7, and 10 | Attenuation of mechanical allodynia | King et al. (2017) [74] | |
| Chemotherapy efficiency—viability, cell death, autophagy, ROS, oxygen concentration, mitochondrial function | colo205 R, DLD-1 R | 4 µM | 10 µM | 6, 12, 24 h | Sensitization of resistant cells | Jeong et al. (2019) [76] | |||
| Tumour growth, autophagy | Female BALB/c nude mice with colo205 R | IP | 10 mg/kg every 2 days | 5 mg/kg every 2 days | Day 18 | Lower tumour weight | |||
| Peripheral sensory neuropathy | Swiss male mice | PO (CBD), IV (L-OHP) | 10 mg/kg, 3 times/week 1 h before L-OHP or in mid-term between L-OHP injections | 2 mg/kg twice a week | Days 28 and 56 | Mechanical hyperalgesia—the tip of a rigid filament 1 week before drug injection, repeated once a week. Cold allodynia—tail immersed in cold water, once a week, 120 s cut-off time |
Attenuation of peripheral sensory neuropathy | Pereira et al. (2021) [75] | |
| CBDCA | Viability, combination index, apoptosis | AXA, Orig, and SH cell lines |
0.03–300 μM; IC50: 5.77, 5.30, and 5.48 μM (and derived concentration series) |
0.01–1 mM; IC50: 384, 529, and 398 μM (and derived concertation series) | 24 h | 0.1% FBS | Antagonistic effect | Inkol et al. (2021) [81] | |
BCNU: carmustine; bFGF: basic fibroblast growth factor; CBD: cannabidiol; CBDCA: carboplatin; CBDA: cannabidiolic acid; CDDP: cisplatin; c: concentration; CT: chemotherapeutics; EGF: epithelial growth factor; EV: extracellular vesicles; GBM: glioblastoma; GSC: glioblastoma stem-like cells; Hu: human; IP: intraperitoneal; IV: intravenous; L-OHP: oxaliplatin; Ms: mouse; NHA: normal human astrocytes; NPCL: neural progenitor cell line; PO: per os; ROS: reactive oxygen species; SC: subcutaneous; TRPV2: transient receptor potential vanilloid 2; TMZ: temozolomide.