Table 2 Therapeutic properties of cannabidiol (CBD) in human cells, bacteria, and animal models
Properties | Experiments/aim | Dose/duration of treatment | Models/population | Results/outcomes | Author & year of publication |
|---|---|---|---|---|---|
Antimicrobial | In vitro activity of CBD when used in combination with polymyxin B (PB) was examined against some Gram-negative bacteria (including Klebsiella pneumoniae, Enterococcus faecium, Acinetobacter baumannii, Pseudomonas aeruginosa) using the standard broth dilution method | 4 µg/mL | Bacterial cells | The growth of these bacteria was inhibited with singular use of CBD but when used in combination with PB, a stronger antibiotic activity was observed | (Abichabki et al. 2021) |
CBD was used in combination with kanamycin against Esherichia coli and Staphylococcus aureus | 1 or 5 µM | Bacterial cells | CBD functioned as an adjuvant agent in increasing antibiotic reaction against microorganisms | (Kosgodage et al. 2019) | |
The antimicrobial activity of CBD against Neisseria gonorrhoeae and S. aureus was studied | 35 µg | Bacterial cells | Neisseria gonorrhoeae was inhibited, and reduction was observed in the growth of S. aureus | (Blaskovich et al. 2021) | |
The antibacterial properties of CBD against Salmonella typhimurium and S. newington was examined through bacterial kinetics, fluorescence microscopy, and biological assays | 0.00125 – 1.25 µg/mL | Bacterial cells | CBD inhibited the growth of S. typhimurium and S. Newington | (Gildea et al. 2022) | |
In vitro assay/microbial susceptibility test to study the effects of cannabinoids on E. coli and S. aureus was conducted | 100 µL | Human cells: alveolar basal epithelial adenocarcinoma (A549), colon adenocarcinoma (Caco-2), hepatoblastoma cell line (Hep G2), epithelial breast adenocarcinoma cell line (MDA-MB-231) and hTERT-immortalized dermal fibroblast cell line (TelCOFS02MA, CRL4005) | Both organisms were susceptible to CBD effects with greater susceptibility seen in S. aureus | (Russo et al. 2021) | |
In vitro/time-kill assay test to determine the effect of combined treatment of CBD and polymyxin against Mycobacterium tuberculosis, S. lugdunensis, Micrococcus luteus, Enterococcus casseliflavus and Rhodococcus equi | 4 µg/mL | Bacterial cells | Combination of CBD and PB inhibited the organisms | (Abichabki et al. 2022) | |
Time-kill assay to determine the potency of CBD against Neisseria gonorrhoeae and Moraxella catarrhalis | 1 – 4 µg/mL | Bacterial cells | CBD displayed excellent activity against biofilms and showed significant antimicrobial activity against the two microorganisms | (Blaskovich et al. 2021) | |
Anti-inflammatory | Examination of the influence of CBD on the interactions of Porphyromonas gingivalis, Filifactor alocis and Treponema denticola with the immune system | 1 µg/mL | Bacterial cells | CBD suppressed pro-inflammatory cytokines (IL-12 p40, IL-8, IL-6 and TNF) induced by P. gingivalis whereas it boosted the production of anti-inflammatory cytokines | (Gu et al. 2019) |
The effect of CBD on immune response markers associated with COVID-19 inflammation was examined in vitro | 5 µg/mL | Human cells: alveolar epithelial cell line (A549), macrophage cell line (KG1) | Significant reduction in the production of IL-6 and IL-8 | (Anil et al. 2021) | |
CBD’s ability to interfere with interleukin (IL-12 and IL-10) production was studied in vivo and in vitro | 15, 30 mg Kg−1 of CBD was administered intraperitoneally, and animals sacrificed after 1 h | Swiss male mice (18-20 g) | The production of IL-12 was enhanced by CBD, whereas it decreased IL-10 production | (Sacerdote et al. 2005) | |
The anti-inflammatory effects of CBD and cannabigerol (CBG), singularly and in combination, were examined against lipopolysaccharide (LPS)-induced pulmonary inflammation | Intraperitoneal or oral administration at 10, 50/100Â mg/kg for one day | Male adult Dunkin-Hartley guinea pigs (250-350Â g) | CBD and CBG showed a clear anti-inflammatory effect in the lung by decreasing the potential of LPS in inducing neutrophil infiltration | (Cabrera et al. 2021) | |
The effect of CBD on cell viability, intracellular calcium, and cytokine production was studied in rheumatoid arthritis synovial fibroblasts |  ≥ 5 µM | Rheumatoid arthritis synovial fibroblasts | CBD increased intracellular calcium, reduced cell viability and IL-6/MMP-3/IL-8 production of rheumatoid arthritis synovial fibroblasts | (Lowin et al. 2020) | |
The reaction of CBD with th17 (characterized by production of interleukin-17) inflammatory autoimmune phenotype was examined | 0.1 – 5 µM | MOG35-55 T cell line established from lymph node cells of C57BL/6 female mice | Significant decrease in the th17 phenotype, a decrease in the secretion of cytokines, including IL-17, whereas the secretion of the anti-inflammatory cytokine IL-10 was enhanced | (Kozela et al. 2013) | |
The effects of CBD on the function of human sebaceous glands were explored | 1 – 10 µM | Human sebocytes | Apart from suppressing sebocyte proliferation, CBD exerted anti-inflammatory effects such as inhibiting the expression of tumour necrosis factor (TNFα) | (Oláh et al. 2014) | |
Antioxidative | Animal model of mania was induced by D-amphetamine (D-AMPH) to investigate CBD effect on amphetamine-induced oxidative stress | Intraperitoneally for 14Â days | Male Wistar rats (250-300Â g) | CBD increased brain-derived neurotrophic factor and protected against D-AMPH-induced oxidative protein damage | (Valvassori et al. 2011) |
Consequence of CBD on oxidative stress, myocardial dysfunction, and interrelated signalling pathways was studied | Intraperitoneal administration of 1, 10/20 mg/kg CBD for 4–11 weeks | Male C57/BL6J Mice | Significant attenuation of oxidative stress observed | (Rajesh et al. 2010) | |
In vivo evaluation was conducted on oxidative stress parameters in the brain and peripheral organs of male Wistar rats to study the effect of acute and extended administration of CBD | 2.5, 5, and 10Â mg/kg CBD was administered intraperitoneally once for the rats in the acute group and for 9Â days for those in the extended group | Male Wistar rats (220-310Â g) | Reduced oxidative stress in both the brain and peripheral organs | (Cassol-Jr et al. 2010) | |
The antioxidant effect of CBD was explored in mice with carbon tetrachloride-induced liver fibrosis | 4 and 8Â mg/kg CBD was administered intraperitoneally twice a week for ten weeks | Male mice (C57BL/6Â J) | Through adjustment of protein expression of gp9l and Nrf2, and suppression of the occurrence of lipid peroxidation, CBD exerted protective effect on CCl4-induced liver fibrosis in mice | (Run et al. 2022) | |
The results of CBD administration in rats irradiated with UV were evaluated | 0.6–62.3 mg of CBD was applied topically for 20 min every 12 h for four weeks | Male nude rats (Hsd: RH-Foxn1rnu, 260-302 g) | CBD penetrated the blood and caused a decrease in reactive oxygen species (ROS) generation as well as an increase in the activity of thioredoxin reductase and glutathione reductase | (Biernacki et al. 2021) | |
The antioxidant effects of cannabidiol were examined in a rat model of ischaemic stroke | 50, 100 and 200Â ng of CBD was administered through intracerebroventricular injection for 5Â days | Male Wistar rats (230-330Â g) | At a dose of 100Â ng/rat, CBD reduced the malondialdehyde level in rat brain as well as the infarction volume. It increased the activity of superoxide dismutase in the striatum and cortex | (Khaksar et al. 2022) | |
The effect of CBD in a mouse model of cisplatin-induced nephropathy was investigated | Intraperitoneal administration of CBD at 2.5 – 10 mg/kg for 3 days | Mice | By chelating transition metal ions, which were involved in the Fenton reaction, to form extremely reactive hydroxyl radicals, CBD was observed to reduce ROS. It also minimized oxidative conditions by inhibiting the formation of superoxide radicals, which were greatly produced by xanthine oxidase (XO) and NADPH oxidase (NOX4 and NOX1) | (Pan et al. 2009) | |
Neuroprotective | Neuroprotective prospects of CBD were examined in the cortical neuron of rat cultures exposed to toxic levels of glutamate in vitro | 2 – 4 µM | Female Wistar rat | CBD reduced glutamate toxicity | (Hampson et al. 1998) |
The potential of CBD to treat ethanol-induced neurodegeneration was conducted in vivo; neurodegeneration was assessed using fluoro-JadeB (FJB) | Transdermal gel application/intraperitoneal injection (20Â mg/kg) twice daily for 3Â days | Sprague Dawley rats (275-300Â g) | FJB cells (neurodegeneration) reduced significantly after transdermal administration of 5% CBD | (Liput et al. 2013) | |
The effect of CBD was examined in hypoxic-ischaemic newborn piglets; brain damage was studied by near-infrared spectroscopy | Singular and intraperitoneal administration of 0.1 mg/kg | Piglets | CBD administration after hypoxia–ischaemia reduced short-term brain damage | (Alvarez et al. 2008) | |
A study was conducted to determine CBD effects on dopaminergic neurodegeneration of Parkinson’s disease using Caenorhabditis elegans | 0.025, 0.05 and 0.1 mM | C. elegans | CBD enhanced lipid deposition thereby enhancing proteasome activity and reducing oxidative stress through the antioxidative pathway | (Muhammad et al. 2022) | |
The neuroprotective effects of CBD were examined in rat model of Parkinson’s disease | 3 mg/kg intraperitoneal administration for 2 weeks | Male Sprague–Dawley rats (≈250 g) | CBD provided neuroprotection against the degeneration of nigrostriatal dopaminergic neurons occurring in Parkinson’s disease | (GarcÃa-Arencibia et al. 2007) | |
The roles of CBD and CBG were examined in the regulation of hypothalamic neuromodulators | 1000Â nM | Rat hypothalamic hypo-E22 cells | CBD inhibited pro-opiomelanocortin, reduced the synthesis of hypothalamic norepinephrine, and reduced dopamine release | (di Giacomo et al. 2020) | |
The therapeutic time window of the neuroprotective effects of CBD was tested in newborn hypoxic-ischaemic (HI) brain damage | 1Â mg/kg was administered subcutaneously for 7Â days | C57BL6 Mice | CBD reduced ipsilateral hemisphere volume loss (IVHL), astrocyte damage, apoptotic damage. It also inhibited microglial population induced by HI | (Mohammed et al. 2017) | |
Pro-apoptotic, anti-proliferative anti-migratory, and anti-invasive effects | A study was conducted to determine the potency of CBD in reducing metastasis in vivo | 1.5 µM | Human breast cancer cells (MDA-MB231) | CBD inhibited human breast cancer cell proliferation and invasion through differential modulation of the extracellular signal-regulated kinase, and reactive oxygen species pathways. It reduced primary tumour mass and lung metastatic foci | (McAllister et al. 2011) |
The impact of CBD on cancer cell invasion was examined using Matrigel invasion assays | 10 µM | Human cells: HeLa, C33A and A549 | CBD inhibited invasion of cancer cells via upregulation of tissue inhibitor of matrix metalloproteinases; invasion was reversed by antagonists to CB1 and CB2, and TRPV1 | (Ramer et al. 2010) | |
The consequences were investigated of the effect of CBD on neonatal iron overload on proteins, such as cytochrome c and Caspase 8, 9, and 3, which are involved in apoptotic pathways | 10Â mg/kg CBD administered intraperitoneally for 14Â days consecutively | Pregnant Wistar rats | CBD reversed the increase in caspase 9,3 and cytochrome c caused by iron overload. It also displayed anti-apoptotic action | (da Silva et al. 2018) | |
To investigate the ability of CBD in modifying the proapoptotic effects of UV irradiation in vitro | 4 µM | Healthy and psoriatic human keratinocytes | Reduction in the apoptotic pathways, which was activated by UVB treatment. Inhibition of the expression of phosphorylated-p38 mitogen-activated protein kinase (p-p38), which promotes apoptosis | (Wójcik et al. 2021) |