Pharmacokinetics and tolerability of liposomal synthetic cannabidiol subcutaneous depot in Holstein dairy calves

As animal welfare concerns and pain management awareness in cattle increase, long-term analgesics can become a solution for the treatment of painful husbandry procedures. Cannabidiol (CBD) has anti-inflammatory and analgesic properties. Nevertheless, poor gastrointestinal absorption and first-pass liver metabolism results in low oral bioavailability in humans. The use of injected liposomal-CBD facilitates slow-drug-release, providing prolonged CBD plasma concentrations, with increased bioavailability. Study objectives were to determine preliminary pharmacokinetics and tolerability of a single subcutaneous injection of liposomal synthetic CBD (L-sCBD; 5 mg/kg) in 6 Holstein female neonatal calves. Blood was sampled for CBD and its metabolites, complete blood count, serum chemistry and serum amyloid A up to 6-wk. Vital signs and adverse effects were monitored. Data over time were compared with baseline using linear regression mixed effects. Plasma CBD concentrations were detected up to a median of 4.5 wk; with median peak plasma concentration (Cmax) 44.1 ng/mL, median time to Cmax 1 d and median half-life 5.3 d. The primary metabolite, 7-carboxy-CBD, exceeded CBD exposure by 9-fold (4-16) based on the area under the curve. A short-term significant neutrophil count increase was observed 2-d postinjection. Serum amyloid A decreased postinjection. The main adverse reaction was local swelling, which spontaneously resolved. Subcutaneous injection of L-sCBD produced detectable CBD plasma concentrations for several wk and was well-tolerated by calves. The use of injectable L-sCBD as an additional long-term analgesic in calves undergoing routine painful procedures (e.g., disbudding, castration) appears to have potential to decrease suffering and promote animal welfare, although further research is required to evaluate efficacy.