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.