Enhancing cannabinoid bioavailability: a crossover study comparing a novel self-nanoemulsifying drug delivery system and a commercial oil-based formulation.

Abstract

Purpose: The oral bioavailability of cannabinoids is limited due to extensive first-pass metabolism, reducing their therapeutic efficacy. This study aimed to evaluate the pharmacokinetics and relative bioavailability of cannabinoids delivered via delta-9-tetrahydrocannabinol/cannabidiol self-emulsifying (THC/CBD-SE) powder, a self-nanoemulsifying drug delivery system, compared to standard oil-based drops.

Methods: Fourteen healthy volunteers (3 men, 11 women) participated in a crossover study. Each received a single oral doses of 8 mg THC and 8 mg CBD in both formulations, with a 30-day washout period between treatments. Blood samples were collected at specified intervals post-administration to assess pharmacokinetic parameters, including maximum plasma concentration (Cmax) and time to reach Cmax (Tmax).

Results: THC/CBD-SE Powder significantly enhanced Cmax for THC (32.79 ± 44.37 ng/mL) and its metabolite 11-OH-THC (10.91 ± 6.64 ng/mL) compared to oil-based drops (THC: 10.17 ± 11.41 ng/mL; 11-OH-THC: 4.64 ± 2.55 ng/mL). Similarly, Cmax for 7-OH-CBD was higher with THC/CBD-SE Powder (2.38 ± 1.63 ng/mL vs. 0.86 ± 0.56 ng/mL). Tmax for 11-OH-THC and 7-OH-CBD was shorter with THC/CBD-SE Powder (0.86 ± 0.36 h vs. 4.54 ± 3.44 h and 1.11 ± 0.59 h vs. 4.68 ± 3.38 h, respectively), indicating a faster onset of action. The THC/CBD-SE Powder exhibited over double the relative bioavailability of cannabinoids compared to oil drops, suggesting improved absorption and rapid onset. Both formulations were well tolerated with no serious adverse events.

Conclusion: THC/CBD-SE Powder significantly improves cannabinoid bioavailability and absorption rates compared to oil-based drops, offering a promising oral delivery method for enhanced therapeutic potential.