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.

Keywords: 11-OH-THC; 7-OH-CBD; CBD; Cannabidiol; Cannabinoid bioavailability; Delta-9-tetrahydrocannabinol; Pharmacokinetics; SNEDDS; Self-Nanoemulsifying drug delivery systems; THC.

© 2025. The Author(s).

目的： 由于大麻素类物质在首次通过代谢中被广泛地分解，其口服生物利用度受到限制，从而降低了治疗效果。本研究旨在评估通过自微乳化（THC/CBD-SE）粉末传递的大麻二酚和四氢大麻酚的药代动力学及相对生物利用度，并与标准油基滴剂进行比较。

方法： 十四名健康志愿者（3名男性，11名女性）参与了一项交叉研究。每位受试者分别接受了THC/CBD-SE粉末和油基滴剂的单次口服剂量8毫克THC和8毫克CBD治疗，并且在两次给药之间设置了30天的洗脱期。在给药后指定的时间点采集血样，以评估包括最大血浆浓度（Cmax）和达到最大血浆浓度时间（Tmax）在内的药代动力学参数。

结果： THC/CBD-SE粉末显著提高了THC（32.79 ± 44.37 ng/mL）及其代谢产物11-OH-THC（10.91 ± 6.64 ng/mL）的Cmax值，与油基滴剂相比分别增加了（THC：10.17 ± 11.41 ng/mL；11-OH-THC：4.64 ± 2.55 ng/mL）。同样地，7-OH-CBD在THC/CBD-SE粉末中的Cmax值也更高（2.38 ± 1.63 ng/mL vs. 0.86 ± 0.56 ng/mL）。对于11-OH-THC和7-OH-CBD的Tmax时间，使用THC/CBD-SE粉末的时间更短（分别为0.86 ± 0.36 h vs. 4.54 ± 3.44 h 和 1.11 ± 0.59 h vs. 4.68 ± 3.38 h），表明其起效更快。THC/CBD-SE粉末的大麻素相对生物利用度比油基滴剂高出两倍以上，提示有更高的吸收效率和快速的起效时间。两种制剂均具有良好耐受性，并未报告严重不良事件。

结论： THC/CBD-SE粉末显著提高了大麻素类物质的生物利用度及吸收速率，与油基滴剂相比具有更好的治疗潜力，为口服给药提供了一种有前景的方法。

关键词： 11-OH-THC；7-OH-CBD；CBD；大麻二酚；大麻素生物利用度；Delta-9-四氢大麻酚；药代动力学；SNEDDS；自纳米乳化药物递送系统；THC。