Regulatory Trends of Organophosphate and Pyrethroid Pesticides in Cannabis and Applications of the Comparative Toxicogenomics Database and Caenorhabditis elegans.

Organophosphate and pyrethroid pesticides are common contaminants in cannabis. Due to the status of cannabis as an illicit Schedule I substance at the federal level, there are no unified national guidelines in the U.S. to mitigate the health risk of pesticide exposure in cannabis. Here, we examined the change in the state-level regulations of organophosphate and pyrethroid pesticides in cannabis. The medians of pyrethroid and organophosphate pesticides specified by each state-level jurisdiction increased from zero pesticide in 2019 to 4.5 pyrethroid and 7 organophosphate pesticides in 2023, respectively. Next, we evaluated the potential connections between pyrethroids, organophosphates, cannabinoids, and Parkinson's disease using the Comparative Toxicogenomics Database (CTD). Eleven pyrethroids, 30 organophosphates, and 14 cannabinoids were associated with 95 genes to form 3,237 inferred and curated Chemical-Gene-Phenotype-Disease tetramers. Using a behavioral repulsion assay with the whole organism model Caenorhabditis elegans, we examined the effect of cannabinoids and insecticides on depleting dopamine synthesis. Exposure to chlorpyrifos and permethrin, but not Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), results in dose-dependent effects on 1-nonanol repulsive behaviors in C. elegans, indicating dopaminergic neurotoxicity (p < 0.01). Dose-dependent effects of chlorpyrifos are different in the presence of Δ9-THC and CBD (p < 0.001). As a proof of concept, this study demonstrated how to use new approach methodologies such as C. elegans and the CTD to inform further testing and pesticide regulations in cannabis by chemical class.