Products containing cannabidiol (CBD) have proliferated after the 2018 Farm Bill legalized hemp (cannabis with ≤0.3% delta-9-tetrahydrocannabinol, Δ9-THC). CBD-containing topical products have surged in popularity but controlled clinical studies on them are limited. This study characterized the effects of five commercially available hemp-derived high CBD/low Δ9-THC topical products. Healthy adults (N=46) received one of six study drugs: a CBD-containing cream (N =8), lotion (N =8), patch (N =7), balm (N=8), gel (N =6), or placebo (N=9; matched to an active formulation). The protocol included three phases conducted over 17 days: 1) an acute drug application laboratory session; 2) a 9-day outpatient phase with twice daily product application (visits occurred on Days 2, 3, 7, and 10); and 3) a 1-week washout phase. In each phase, whole blood, oral fluid, and urine specimens were collected and analyzed via liquid chromatography with tandem mass spectrometry (LC-MS/MS) for CBD, Δ9-THC, and primary metabolites of each and pharmacodynamic outcomes (subjective, cognitive/psychomotor, physiological effects) were assessed. Transdermal absorption of CBD was observed for three active products. On average, CBD/metabolite concentrations peaked after 7-10 days of product use and were highest for the lotion, which contained the most CBD and a permeation enhancer (vitamin E). Δ9-THC/metabolites were below the limit of detection in blood for all products and no urine samples tested “positive” for cannabis using current U.S. federal workplace drug testing criteria (immunoassay cutoff of 50ng/mL and confirmatory LC-MS/MS cutoff of 15ng/mL). Unexpectedly, nine participants (seven lotion, one patch, one gel) exhibited Δ9-THC oral fluid concentrations ≥ 2ng/mL (current U.S. federal workplace threshold for a “positive” test). Products did not produce discernable pharmacodynamic effects and were well-tolerated. This study provides important initial data on the acute/chronic effects of hemp-derived topical CBD products, but more research is needed given the diversity of products in this market.

中文翻译：

---

五种不同市售大麻衍生外用大麻二酚 (CBD) 产品的药代动力学和药效学

2018 年农业法案使大麻（δ9-四氢大麻酚，Δ9-THC 含量≤0.3% 的大麻）合法化后，含有大麻二酚 (CBD) 的产品激增。含有 CBD 的外用产品越来越受欢迎，但对其进行的对照临床研究却很有限。这项研究表征了五种市售大麻衍生的高 CBD/低 Δ9-THC 外用产品的效果。健康成年人 (N = 46) 接受六种研究药物之一：含 CBD 的乳膏 (N = 8)、乳液 (N = 8)、贴剂 (N = 7)、香膏 (N = 8)、凝胶 (N = 6) 或安慰剂（N=9；与活性制剂匹配）。该方案包括在 17 天内进行的三个阶段：1）急性药物应用实验室会议；2) 为期 9 天的门诊阶段，每天两次使用产品（第 2、3、7 和 10 天就诊）；3) 1 周的清除阶段。在每个阶段，收集全血、口腔液和尿液样本，并通过液相色谱串联质谱法 (LC-MS/MS) 分析 CBD、Δ9-THC 和每种药物的主要代谢物以及药效学结果（主观、认知） /精神运动、生理效应）进行了评估。观察到三种活性产品的 CBD 透皮吸收。平均而言，CBD/代谢物浓度在产品使用 7-10 天后达到峰值，并且乳液中的浓度最高，其中含有最多的 CBD 和渗透增强剂（维生素 E）。所有产品的 Δ9-THC/代谢物均低于血液中的检测限，并且使用现行美国联邦工作场所药物检测标准（免疫测定截止值为 50ng/mL，确认性 LC-MS/MS 截止值为15纳克/毫升）。出乎意料的是，9 名参与者（7 种洗剂、1 种贴剂、1 种凝胶）表现出 Δ9-THC 口腔液浓度 ≥ 2 ng/mL（当前美国联邦工作场所“阳性”测试阈值）。产品没有产生明显的药效作用并且耐受性良好。这项研究提供了有关大麻衍生外用 CBD 产品的急性/慢性影响的重要初步数据，但鉴于该市场产品的多样性，还需要进行更多研究。