Toxicological safety of VOHO Hemp Oil; a supercritical fluid extract from the aerial parts of hemp

Dziwenka, Margitta M.; Dolan, Laurie C.; Mitchell, James

doi:10.1371/journal.pone.0261900

Cited by 10 publications

(25 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From the studies assessed by EFSA [7], only 3 animal studies were identified with suitable dose-response data for benchmark dose modelling, and additionally a study of Dziwenka et al [9] was included. Two of the studies (GWTX1412 and GWTX1413) were published in the context of the approval process of the CBD medicinal product Epidiolex as part of the application review files on the US Food and Drug Administration (FDA) website [13].…”

Section: Resultsmentioning

confidence: 99%

“…As the extract was of a comparably high purity of CBD, the authors decided to still include the study for comparative reasons. Similarly, Dziwenka et al [9,15] recently provided 2 studies of hemp extracts; while the 2020 study [15] did not provide raw data necessary for BMD modelling, the 2021 study [9] was included for comparative reasons as well.…”

Section: Resultsmentioning

confidence: 99%

“…j Data shown for comparative reasons only because CBD was applied in the form of a hemp mixture with other phytochemicals. k The study of Dziwenka et al [9] was conducted with a hemp oil extract containing 28.14% cannabinoids and 25.2% CBD. The levels were adjusted to reflect pure CBD.…”

Section: Resultsmentioning

confidence: 99%

“…The data analysed in this study were obtained from the EFSA statement [7]. No additional searches for data were conducted, apart from inclusion of another informative study of Dziwenka et al [9] not included by EFSA. The data were checked for the suitability of benchmark dose-response modelling according to the criteria of Hindelang et al [10]: (i) a study considered for inclusion in this research had to have administered at least 3 different doses and a control group receiving vehicle, while dose spacing was not considered relevant, (ii) applied doses had to be administered in mg/kg of body weight, (iii) the number of animals per dose group had to be declared, and (iv) studies reporting concomitant treatment with other medications were not included.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Does Cannabidiol (CBD) in Food Supplements Pose a Serious Health Risk? Consequences of the EFSA Clock Stop Regarding Novel Food Authorisation

Lachenmeier¹,

Sproll²,

Golombek³

et al. 2022

Preprint

View full text Add to dashboard Cite

At present, foods containing cannabidiol (CBD) and other cannabinoids are internationally being widely advertised and sold in increasing quantities. In the European Union (EU), these products require pre-marketing authorisation under the novel food regulation, so that all available CBD oils and CBD-containing food supplements in the EU are currently placed on the market with an infringement of the food laws. Currently, 19 CBD applications are under assessment at the European Food Safety Authority (EFSA). During the initial assessment of the application files, EFSA located several knowledge gaps that need to be addressed before the safety evaluation of CBD can be concluded. Namely, the effect of CBD on the liver, gastrointestinal tract, endocrine system, nervous system, psychological function, and reproductive system needs to be clarified. Nevertheless, the available literature allows a benchmark dose (BMD)-response modelling of several bioassays, resulting in a BMD lower confidence limit (BMDL) of 20 mg/kg bw/day for liver toxicity in rats. Human data in healthy volunteers found increases in the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a study at 4.3 mg/kg bw/day, which was defined by EFSA as a lowest observed adverse effect level (LOAEL). The EFSA panel currently concluded that the safety of CBD as a novel food cannot be evaluated, leading to a so-called clock stop of the applications until the applicants provide the required data. Meanwhile, the authors suggest that CBD products still available on the EU market despite the lack of authorisation must be considered as “unsafe”. Products exceeding a reference dose of 10 mg/day must be considered as being “unfit for consumption” (Article 14(1) and (2) (b) of Regulation No 178/2002), while the ones in exceedance of the human LOAEL must be considered “injurious to health” (Article 14(1) and (2) (a) of Regulation No 178/2002).

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Does Cannabidiol (CBD) in Food Supplements Pose a Serious Health Risk? Consequences of the EFSA Clock Stop Regarding Novel Food Authorisation

Lachenmeier¹,

Sproll²,

Golombek³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The data analysed in this study were obtained from the statement of the EFSA NDA panel [7]. No additional searches for data were conducted, apart from inclusion of another informative study of Dziwenka et al [9] not included in the EFSA statement [7].…”

Section: Methodsmentioning

confidence: 99%

Does Cannabidiol (CBD) in Food Supplements Pose a Serious Health Risk? Consequences of the EFSA Clock Stop Regarding Novel Food Authorisation

Lachenmeier¹,

Sproll²,

Golombek³

et al. 2022

Preprint

View full text Add to dashboard Cite

In the European Union (EU), cannabidiol products require pre-marketing authorisation under the novel food regulation. Currently, 19 CBD applications are under assessment at the European Food Safety Authority (EFSA). During the initial assessment of the application files, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) located several knowledge gaps in their 07 June 2022 statement on safety of cannabidiol as a novel food that need to be addressed before the evaluation of CBD can be concluded. Namely, the effect of CBD on the liver, gastrointestinal tract, endocrine system, nervous system, psychological function, and reproductive system needs to be clarified. Nevertheless, the available literature allows a benchmark dose (BMD)-response modelling of several bioassays, resulting in a BMD lower confidence limit (BMDL) of 20 mg/kg bw/day for liver toxicity in rats. Human data in healthy volunteers found increases in the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a study at 4.3 mg/kg bw/day, which was defined by EFSA NDA panel as a lowest observed adverse effect level (LOAEL). The EFSA NDA panel currently concluded that the safety of CBD as a novel food cannot be evaluated, leading to a so-called clock stop of the applications until the applicants provide the required data. Meanwhile, the authors suggest that CBD products still available as food supplements on the EU market despite the lack of authorisation must be considered as “unsafe”. Products exceeding a health-based guidance value of 10 mg/day must be considered as being “unfit for consumption” (Article 14(1) and (2) (b) of Regulation No 178/2002), while the ones in exceedance of the human LOAEL must be considered “injurious to health” (Article 14(1) and (2) (a) of Regulation No 178/2002).

show abstract

An evaluation of the genotoxicity and 90‐day repeated‐dose toxicity of a CBD‐rich hemp oil

Clewell,

Glávits,

Endres

et al. 2023

J of Applied Toxicology

View full text Add to dashboard Cite

Currently, there is much interest in the sales and study of consumable Cannabis sativa L. products that contain relatively high levels of cannabidiol (CBD) and low levels of Δ‐9‐tetrahydrocannabinol. While there are published safety evaluations for extracts containing low concentrations of CBD, toxicological assessments for those with higher concentrations are still scant in the public domain. In this paper, genotoxicity tests and a 90‐day repeated‐dose toxicity study of an ethanolic extract of C. sativa containing ~85% CBD were performed following relevant OECD guidelines. No increased gene mutations were observed in a bacterial reverse mutation assay compared to controls up to the maximum recommended concentration of the guideline. An in vitro chromosomal aberration assay showed no positive findings in the short‐term (3 h) treatment assays. Long‐term treatment (20 h) showed an increased number of cells containing aberrations at the highest dose of 2 μg/mL, which was outside of historical control levels, but not statistically significantly different from the controls. An in vivo micronucleus study showed no genotoxic potential of the test item in mice. A 90‐day repeated‐dose gavage study using 0, 75, 125, and 175 mg/kg bw/day showed several slight findings that were considered likely to be related to an adaptive response to consumption of the extract by the animals but were not considered toxicologically relevant. These included increases in liver and adrenal weights compared to controls. The NOAEL was determined as 175 mg/kg bw/day, the highest dose tested (equivalent to approximately 150 mg/kg bw/day of CBD).

show abstract

Toxicological safety of VOHO Hemp Oil; a supercritical fluid extract from the aerial parts of hemp

Cited by 10 publications

References 10 publications

Does Cannabidiol (CBD) in Food Supplements Pose a Serious Health Risk? Consequences of the EFSA Clock Stop Regarding Novel Food Authorisation

Does Cannabidiol (CBD) in Food Supplements Pose a Serious Health Risk? Consequences of the EFSA Clock Stop Regarding Novel Food Authorisation

Does Cannabidiol (CBD) in Food Supplements Pose a Serious Health Risk? Consequences of the EFSA Clock Stop Regarding Novel Food Authorisation

An evaluation of the genotoxicity and 90‐day repeated‐dose toxicity of a CBD‐rich hemp oil

Contact Info

Product

Resources

About