Nematicidal effects of hemp (Cannabis sativa) may not be mediated by cannabinoid receptors

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Abstract
Few nematodes infest the roots of hemp (Cannabis sativa L.) plants, and hemp plant extracts have been utilised as botanical nematicides. The responsible constituent may be δ9‐tetrahydrocannabinol (δ9‐THC). In humans, δ9‐THC exerts its effects via a family of G protein‐coupled receptors, known as cannabinoid (CB) receptors. CB receptors are phylogenetically ancient, and occur in many vertebrates and invertebrates. We therefore searched for evidence of CB receptors in nematodes. All nematode cDNA sequences at GenBank, including the entire genome of Caenorhabditis elegans, were screened for homologs of human CB receptors using BLAST 2.0 as a sequence alignment search engine. We also searched for homologs of fatty acid amide hydrolase (FAAH), the enzyme in vertebrates that metabolises the endogenous ligands of CB receptors. Several C. elegans gene products with low homology to CB receptors and FAAH were identified. Close examination of these sequences revealed crippling substitutions at critical amino acid residues. These results suggest the genes for CB receptors are absent in C. elegans, and the nematicidal activities of δ9‐THC and Cannabis are not mediated through CB receptors.