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Low doses of widely consumed cannabinoids (cannabidiol and cannabidivarin) cause DNA damage and chromosomal aberrations in human-derived cells

Cannabidiol (CBD) and cannabidivarin (CBDV) are natural cannabinoids which are consumed in increasing amounts worldwide in cannabis extracts, as they prevent epilepsy, anxiety, and seizures. It was claimed that they may be useful in cancer therapy and have anti-inflammatory properties. Adverse long-term effects of these drugs (induction of cancer and infertility) which are related to damage of the genetic material have not been investigated. Therefore, we studied their DNA-damaging properties in…

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. 2019 Jan;93(1):179-188.

doi: 10.1007/s00204-018-2322-9. Epub 2018 Oct 19.

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Chiara Russo et al. Arch Toxicol. .

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Abstract

Cannabidiol (CBD) and cannabidivarin (CBDV) are natural cannabinoids which are consumed in increasing amounts worldwide in cannabis extracts, as they prevent epilepsy, anxiety, and seizures. It was claimed that they may be useful in cancer therapy and have anti-inflammatory properties. Adverse long-term effects of these drugs (induction of cancer and infertility) which are related to damage of the genetic material have not been investigated. Therefore, we studied their DNA-damaging properties in human-derived cell lines under conditions which reflect the exposure of consumers. Both compounds induced DNA damage in single cell gel electrophoresis (SCGE) experiments in a human liver cell line (HepG2) and in buccal-derived cells (TR146) at low levels (≥ 0.2 µM). Results of micronucleus (MN) cytome assays showed that the damage leads to formation of MNi which reflect chromosomal aberrations and leads to nuclear buds and bridges which are a consequence of gene amplifications and dicentric chromosomes. Additional experiments indicate that these effects are caused by oxidative base damage and that liver enzymes (S9) increase the genotoxic activity of both compounds. Our findings show that low concentrations of CBD and CBDV cause damage of the genetic material in human-derived cells. Furthermore, earlier studies showed that they cause chromosomal aberrations and MN in bone marrow of mice. Fixation of damage of the DNA in the form of chromosomal damage is generally considered to be essential in the multistep process of malignancy, therefore the currently available data are indicative for potential carcinogenic properties of the cannabinoids.

Keywords: CBD; CBDV; Genotoxicity; MN assay; SCGE assay.

Conflict of interest statement

The authors state that they have no conflict of interest.

Figures

Fig. 1

Fig. 1

Chemical structure of the test compounds. a ∆9-THC (CAS Nr. 1972-08-3), b CBD (CAS Nr. 13956-29-1), c CBDV (CAS Nr. 24274-48-4) is a propyl derivative of CBD

Fig. 2

Fig. 2

a, b Induction of DNA damage by CBD and CBDV in a human-derived liver cell line (HepG2). The cells were treated with different concentrations of the test compounds for 3 and 24 h. Methanol was used as a solvent control [for 3 h CBD: 1.70% (v/v) and CBDV: 1.55% (v/v); for 24 h CBD: 0.56% (v/v) for CBDV: 0.52% (v/v)]. Hydrogen peroxide (50 µM) was used as a positive control (the cells were treated for 5 min on ice) and induced clear positive effects (26.57 ± 3.64% DNA in tail). Bars indicate means ± SD of results obtained with two parallel cultures per experiment (from each culture two slides were made and 50 cells were evaluated per slide). Stars indicate statistical significance (p ≤ 0.05, ANOVA). All statistical calculations are based on comparisons between results which were obtained with cells which had been treated with the test compounds and results which were obtained with corresponding solvent controls

Fig. 3

Fig. 3

a, b Induction of DNA damage by CBD and CBDV in a human-derived buccal cell line (TR146). The cells were treated with different concentrations of the test compounds for 3 h. Methanol was used as solvent control [CBD: 1.70% (v/v) and CBDV: 1.55% (v/v)]. Hydrogen peroxide (50 µM) was used as a positive control (the cells were treated for 5 min on ice). The peroxide induced clear positive effects (20.12 ± 1.84% DNA in tail). Bars indicate means ± SD of results obtained with two parallel cultures per experiment (from each culture two slides were made and 50 cells were evaluated per slide). Stars indicate statistical significance (p ≤ 0.05, ANOVA). All statistical calculations are based on comparisons between results which were obtained with cells which had been treated with the test compounds and results which were obtained with corresponding solvent controls

Fig. 4

Fig. 4

a, b Impact of liver enzyme homogenate on the DNA-damaging activity of CBD and CBDV in TR146 cells. The cells were treated with 2.0 µM of the cannabinoids and in parallel with liver enzyme homogenate (for details see “Materials and methods”). Bars indicate means ± SD of results obtained with two parallel cultures per experiment (from each culture two slides were made and 50 cells were evaluated per slide). Stars indicate statistical significance (p ≤ 0.05, Two-tailed paired t test). All statistical calculations are based on comparisons between results which were obtained with cells which had been treated with the test compounds and results which were obtained with corresponding solvent controls

Fig. 5

Fig. 5

a, b Formation of oxidized purines in HepG2 cells by CBD and CBDV. The cells were exposed to the test compounds for 3 h. Subsequently, the nuclei were isolated after lysis and treated with FPG or with the corresponding buffers before electrophoresis for 30 min. Bars indicate means ± SD of results obtained with two cultures per experimental point. From each culture, two slides were made and 50 cells were evaluated per slide. Stars indicate statistical significance (p ≤ 0.05, ANOVA). All statistical calculations are based on comparisons between results which were obtained with cells which had been treated with the test compounds and results which were obtained with corresponding solvent controls

Fig. 6

Fig. 6

a, b Formation of oxidized pyrimidines in HepG2 cells by CBD and CBDV. The cells were exposed to the test compounds for 3 h. Subsequently, the nuclei were isolated after lysis and treated with ENDO III or with the corresponding buffers before electrophoresis for 45 min. Bars indicate means ± SD of results obtained with two cultures per experimental point. From each culture, two slides were made and 50 cells were evaluated per slide. Stars indicate statistical significance (p ≤ 0.05, ANOVA). All statistical calculations are based on comparisons between results which were obtained with cells which had been treated with the test compounds and results which were obtained with corresponding solvent controls

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References

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What is one of the strongest CBD in vaping form?

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Visit our community site for vetted suppliers at http://theCBD.place. It’s time that this subject was given more internet exposure. We are here to discuss topics related to medical marijuana and our experiences using CBD. Please do not assume that anyone here is a medical professional.

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Anzac Day march increased to 5000 in Sydney's CBD

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Any veteran who wishes to participate in the Sydney CBD march will be required to register via the RSL NSW website.

In previous years, veterans and their descendants have not been required to register to march, with more than 12,000 taking to Sydney’s streets in 2019.

Earlier on Tuesday, Mr Morrison said he would like to see Anzac Day celebrations “return to normal as much as we possibly can”.

“I respect ultimately these are calls that have got to be made by state governments, but I want Anzac Day on,” he told reporters in Sydney.

“If people can party, and if people can protest, then we can remember as a nation and honour our veterans on Anzac Day. And I would like to see that done as fully and as safely as possible.”

In 2020, Anzac Day marches across Australia were cancelled as the nation entered strict coronavirus restrictions. In lieu of the march, “Light Up the Dawn” driveway services were held in neighbourhoods across the country.

Tuesday marked NSW’s 51st consecutive day of no locally acquired coronavirus cases.

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Source: https://www.google.com/url?rct=j&sa=t&url=https://www.smh.com.au/national/nsw/anzac-day-march-increased-to-5000-in-sydney-s-cbd-20210309-p5792r.html&ct=ga&cd=CAIyGjQ2MzM1ZTBkNWQyZmIyYzc6Y29tOmVuOlVT&usg=AFQjCNGJKXeFEPybOePsWcm_wHfdMbTZww

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Anzac Day march increased to 5000 in Sydney's CBD

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The Anzac Day march in Sydney's CBD will be capped at 5000 after RSL NSW reached an agreement with the NSW government and police to … Checkout PrimeXBT
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