The toxicology of orally administered Δ⁹-tetrahydrocannabinol in sheep

Introduction: As part of a larger study to assess the potential value of industrial hemp biomass (the low Δ9-tetrahydrocannabinol (Δ9-THC) variety of Cannabis sativa L.) as a feed for ruminants, a pharmacokinetics study of Δ9-THC, one of the main cannabinoids of interest, was undertaken. In undertaking this study, the toxicology of orally administered Δ9-THC was incidentally investigated and was discussed in the current paper. Methods: Eight Merino ewes were administered with two per os (PO) doses of 88.5 mg Δ9-THC/kg bodyweight (BW) 12 h apart. Blood samples were taken periodically to determine the pharmacokinetics of Δ9-THC but also to check blood troponin I concentrations post dose administration as in the pharmacokinetics study there were adverse effects to the heart following intravenous administration of Δ9-THC. Results: Following the PO dose of Δ9-THC, the pharmacokinetics were able to be determined (and were published separately); however, significant adverse clinical signs were observed in the sheep. Clinical signs included ataxia (stumbling, swaying), abnormal posture (head held low, head resting on the wall of the pen, back legs crossed over), somnolence, wool pulling, increased salivation, a prolonged reduction in feed intake and consequent decrease in BW. Plasma troponin I concentrations were elevated in three of the eight sheep following the PO dose of Δ9-THC. Conclusions: The adverse clinical signs noted have implications for iHemp biomass as a potential feed for ruminants due to both animal health and production effects. Further research is required to investigate appropriate feeding strategies for iHemp biomass to be utilised as a feed for ruminants.