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ORIGINAL RESEARCH article

Front. Toxicol.
Sec. Developmental and Reproductive Toxicology
Volume 6 - 2024 | doi: 10.3389/ftox.2024.1469341
This article is part of the Research Topic The toxicology of cannabis and cannabis-based products View all articles

Assessment of the effects of cannabidiol (CBD) and a CBD-rich hemp extract in Caenorhabditis elegans

Provisionally accepted
Jessica A. Camacho Jessica A. Camacho Bonnie Welch Bonnie Welch Martine Ferguson Martine Ferguson Estatira Sepehr Estatira Sepehr Cory Vaught Cory Vaught Yang Zhao Yang Zhao Suzanne Fitzpatrick Suzanne Fitzpatrick Jeffrey Yourick Jeffrey Yourick Robert Sprando Robert Sprando Piper R. Hunt Piper R. Hunt *
  • Center for Food Safety and Applied Nutrition, United States Food and Drug Administration, College Park, Maryland, United States

The final, formatted version of the article will be published soon.

    Consumer use of cannabidiol (CBD) is growing, but there are still data gaps regarding possible adverse effects of CBD on reproduction and development. Multiple pathways and signaling cascades involved in organismal development and neuronal function, including endocannabinoid synthesis and signaling systems, are well conserved across phyla, suggesting that Caenorhabditis elegans can model in vivo effects of exogenous cannabinoids. Effects in C. elegans on oxidative stress response (OxStrR), developmental timing, juvenile and adult spontaneous locomotor activity, reproductive output, and organismal CBD concentrations were assessed after exposures to purified CBD or a hemp extract suspended in 0.5% sesame oil emulsions. In C. elegans, this emulsion vehicle is equivalent to a high-fat diet (HFD). As in mammals, HFD was associated with oxidative stress related gene expression in C. elegans adults. CBD reduced HFD-induced OxStrR in transgenic adults and counteracted the hypoactivity observed in HFD exposed wild-type adults. In C. elegans exposed to CBD from the onset of feeding, delays to later milestone acquisition were irreversible, while later juvenile locomotor activity effects were reversible with removal of CBD exposure. CBD-induced reductions in mean juvenile population body size were cumulative when chronic exposures were initiated at parental reproductive maturity. Purified CBD was slightly more toxic than matched concentrations of CBD in hemp extract for all tested endpoints, and both were more toxic to juveniles than to adults. Dosimetry indicated that all observed C. elegans adverse effect levels far exceeded recommended CBD dosing for humans.1%Tw80: 1% Tween (polysorbate) 80 in non-fat cows' milk 0.1%Tw80: a 1:9 mix of 1%Tw80 in CeHM

    Keywords: Cannabidiol, hemp extract, C. elegans, alternative in vivo toxicity test model, irreversible developmental effect, chronic exposure effects Indent: Left: -0.25" Formatted: Indent: Left: 0.25" Formatted: Font: Italic Formatted: Font: Italic Formatted: Font: Italic

    Received: 23 Jul 2024; Accepted: 27 Aug 2024.

    Copyright: © 2024 Camacho, Welch, Ferguson, Sepehr, Vaught, Zhao, Fitzpatrick, Yourick, Sprando and Hunt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Piper R. Hunt, Center for Food Safety and Applied Nutrition, United States Food and Drug Administration, College Park, 20740, Maryland, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.