2023 FDA Science Forum
Assessment of the effects of cannabidiol (CBD) in the alternative toxicity model Caenorhabditis elegans.
- Authors:
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Contributing OfficeCenter for Food Safety and Applied Nutrition
Abstract
Background:
Edible products that contain cannabinoid compounds (CCs) and extracts are widely available, and sales are increasing in the United States. Some CCs, such as cannabidiol (CBD), are well studied, but less information is available on the effects of other CCs and cannabinoid plant extracts. Many pathways and signaling cascades involved in organismal development and neuronal function, including endocannabinoid synthesis and signaling systems, are well conserved from worms to people. Studies have demonstrated concordant effects on mammals and the microscopic nematode C. elegans for chemical modes of action, as well as for apical endpoints such as developmental delay and locomotor activity changes, indicating that the C. elegans model may be useful in filling data gaps on the effects of CCs and their mixtures.
Purpose:
Complex biological processes such as organismal development and chemically induced neurobehavioral effects cannot be fully modeled with currently available in vitro and microphysiological systems. This study in progress is being conducted using C. elegans to help fill data gaps on the effects of CCs and a hemp extract.
Methodology:
Effects in C. elegans on oxidative stress response (OxStrR), unfolded protein response (UPR), developmental timing, juvenile spontaneous locomotor activity, and reproductive output have so far been assessed for CBD at exposures of 25-500µg/mL.
Results:
In C. elegans adults, CBD reduced OxStrR and UPR pathways in a dose-response manner. No effects on gross morphology or progeny-to-adult ratios were identified at exposures up to 500µg/mL. In juvenile C. elegans, there was mild hypoactivity at 200-500µg/mL exposures, and a non-significant trend to developmental delay only at the highest exposure of 500µg/mL.
Conclusions:
While toxicity in humans cannot be ruled out using C. elegans data alone, the model has high positive prediction rates for mammalian developmental toxicants, neurotoxicants, and conserved modes of chemical action. CBD had no effect on C. elegans reproductive output, but induced slight hypoactivity in developing C. elegans, consistent with mild sedation. As in mammalian cell cultures, CBD reduced OxStrR and UPR in C. elegans. These results suggest that the effects of other CCs and hemp extract planned for assessment in this study may also be conserved.
