Effect of Cannabidiol on the Long-Term Toxicity and Lifespan in the Preclinical Model Caenorhabditis elegans

dc.creatorLand, M. Hunter
dc.creatorToth, Marton L.
dc.creatorMacNair, Laura
dc.creatorVanapalli, Siva A. (TTU)
dc.creatorLefever, Timothy W.
dc.creatorPeters, Erica N.
dc.creatorBonn-Miller, Marcel O.
dc.date.accessioned2022-04-21T20:51:17Z
dc.date.available2022-04-21T20:51:17Z
dc.date.issued2021
dc.description© M. Hunter Land et al. 2021; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.description.abstractIntroduction: Despite widespread use of cannabidiol (CBD), no lifelong toxicity study has been published to date. Caenorhabditis elegans is often used in preclinical lifelong toxicity studies, due to an estimated 60–80% of their genes having a human ortholog, and their short lifespan of ∼2–3 weeks. In this study, we examined both acute and long-term exposure studies of CBD at physiologically relevant concentrations. Materials and Methods: Acute toxicity was determined by treating day 1 adults with a wide range of CBD concentrations (0.4 μM to 4 mM) and assessing mortality and motility compared to control animals. Thermotolerance was examined by treating adult animals with CBD (0.4 μM to 4 mM) and exposing them to 37°C for 4 h, and then scoring for the number of alive animals treated with CBD compared to controls. Long-term toxicity was assessed by exposing day 1 adults to 10, 40, and 100 μM CBD until all animals perished. Control animals had no active drug exposure. Results: We report both acute and long-term exposure studies of CBD to adult C. elegans at physiologically relevant concentrations. Acute toxicity results showed that no animal died when exposed to 0.4–4000 μM CBD. The thermotolerance study showed that 40 μM CBD, but not other treatment levels, significantly increased resistance to heat stress by 141% compared to the untreated controls. Notably, whole-life exposure of C. elegans to 10–100 μM CBD revealed a maximum life extension of 18% observed at 40 μM CBD. In addition, motility analysis of the same groups revealed an increase in late-stage life activity by up to 206% compared to controls. Conclusion: These results serve as the only CBD lifelong exposure data in an in vivo model to date. While further research into the lifelong use of CBD should be carried out in mammalian models, the C. elegans model indicates a lack of long-term toxicity at physiologically relevant concentrations.en_US
dc.identifier.citationM. Hunter Land, Marton L. Toth, Laura MacNair, Siva A. Vanapalli, Timothy W. Lefever, Erica N. Peters, and Marcel O. Bonn-Miller.Cannabis and Cannabinoid Research.Dec 2021.522-527.http://doi.org/10.1089/can.2020.0103en_US
dc.identifier.urihttps://doi.org/10.1089/can.2020.0103
dc.identifier.urihttps://hdl.handle.net/2346/89129
dc.language.isoengen_US
dc.subjectCannabidiolen_US
dc.subjectToxicityen_US
dc.subjectLifespanen_US
dc.subjectMotilityen_US
dc.subjectAgingen_US
dc.subjectHealthen_US
dc.titleEffect of Cannabidiol on the Long-Term Toxicity and Lifespan in the Preclinical Model Caenorhabditis elegansen_US
dc.typeArticleen_US

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