Pharmacokinetics of Two Nanoemulsion Formulations of Δ⁸-Tetrahydrocannabinol in Rats

The use of Δ⁸-tetrahydrocannabinol (Δ⁸-THC) has increased in recent years. Given that the oral absorption of cannabinoids in oil formulations is typically slow and variable, nanoemulsions may be an improved delivery vehicle. Therefore, we characterized the pharmacokinetics (PK) in Sprague-Dawley rats following the administration of three different oral formulations containing 10 mg/kg Δ⁸-THC: a translucent liquid nanoemulsion, a reconstituted powder nanoemulsion, and a medium chain triglyceride (MCT) oil solution for comparison. Δ⁸-THC was also administered intravenously at 0.6 mg/kg. Plasma samples were quantified for Δ⁸-THC and two metabolites, 11-hydroxy-Δ⁸-THC (11-OH-Δ⁸-THC) and 11-carboxy-Δ⁸-THC (COOH-Δ⁸-THC). Non-compartmental PK parameters were calculated, and a PK model was developed based on pooled data. Despite a smaller median droplet size of the translucent liquid nanoemulsion (26.9 nm) compared to the reconstituted powder nanoemulsion (168 nm), the PK was similar for both. The median T_max values of Δ⁸-THC for the nanoemulsions (0.667 and 1 h) were significantly shorter than the median T_max of Δ⁸-THC in MCT oil (6 h). This resulted in an approximately 4-fold higher Δ⁸-THC exposure over the first 4 h for the nanoemulsions relative to the MCT oil solution. The active 11-OH-Δ⁸-THC metabolite followed a similar pattern to Δ⁸-THC. The non-compartmental bioavailability estimates of Δ⁸-THC for the nanoemulsions (11-16.5%) were lower than for the MCT oil solution (>21.5%). However, a model-based analysis indicated similar bioavailability for all three oral formulations. These results demonstrate favorable absorption properties of both nanoemulsions, despite the difference in droplet sizes, compared to an MCT oil formulation.