Organophosphate and Pyrethroid Pesticides and Cannabis in the United States: Trends in State-level Regulations and Applications of New Approach Methodologies

The presence of pesticide contaminants in cannabis, such as organophosphate and pyrethroid pesticides, has resulted in multiple recalls by manufacturers in the U.S. There are no national guidelines to mitigate the health risk of pesticide exposure in cannabis because it is an illicit Schedule I substance under federal law. Here, we reviewed the state-level regulations of organophosphate and pyrethroid pesticides in cannabis between 2019 and 2023 and found that 14 more jurisdictions (for a total of 29) are regulating organophosphate or pyrethroid pesticides in the U.S. We evaluated the potential connections between pyrethroids, organophosphates, cannabinoids, and Parkinson’s disease using the Comparative Toxicogenomics Database (CTD). 10 pyrethroids, 27 organophosphates, and 15 cannabinoids were associated with 68 genes to form 2,320 inferred and curated Chemical-Gene-Phenotype-Disease tetramers. Exposure to chlorpyrifos and permethrin, but not Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), results in dose-dependent effects on 1-nonanol repulsive behaviors in Caenorhabditis elegans, indicating dopaminergic neurotoxicity (p < 0.01). Dose-dependent effects of chlorpyrifos, but not permethrin, are different in the presence of Δ9-THC and CBD (p < 0.001). Our findings show that (1) U.S. states are reaching a consensus on pesticide regulation in cannabis and (2) regulators need to consider the mechanistic interaction of pesticides and cannabinoids. Further research should apply new approach methodologies such as C. elegans and CTD can help inform pesticide regulation in cannabis by chemical class.