Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Addiction Institute, Mount Sinai Behavioral Health System, New York, New York, USA.
Cannabis Cannabinoid Res. 2024 Aug;9(4):939-966. doi: 10.1089/can.2023.0025. Epub 2023 Aug 29.
In this review, we provide an updated assessment of available evidence on the pharmacokinetics (PK) of CBD and explore the impact of different factors on PK outcomes. This systematic review and meta-regression analysis was preregistered (PROSPERO: CRD42021269857). We systematically searched Medline, Embase, PsycInfo, and Web of Science Core Collection up to November 19, 2022. Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including T, C, AUC, AUC, and T, in serum or plasma. Studies of patient populations or CBD co-administration with other medications were excluded. The was used. Random-effects multivariable meta-regression analysis was conducted. A total of 112 trial arms from 39 studies were included; 26 trial arms had a "Good" quality, 70 "Fair," and 16 "Poor." Eight arms used inhalation CBD, 29 oromucosal, 73 oral, and 2 intravenous. CBD formulations could be categorized to nanotech (=14), oil-based (=21), alcohol-based (=10), water-based (=12), Sativex (=17), and Epidiolex (=22). For single-dose studies, CBD doses ranged between 2 and 100 mg in inhalation, 5-50 mg in oromucosal, and 0.42-6000 mg in oral administration. Sixty-six trial arms had only male participants or a higher number of male than female participants. The duration of the PK session was between 4 and 164 h. A higher CBD dose was associated with higher C, AUC, and AUC. Compared with oral administration, oromucosal administration was associated with lower C, AUC, and AUC. Fed status was associated with higher C and AUC when compared with the fasting status. A higher ratio of female participants was associated with lower T in oral administration and higher C. As expected, CBD dose, route of administration, and diet were major determinants of CBD PK with oral routes providing higher bioavailability and nanotechnology formulations a faster onset. Although CBD appeared to have a faster onset and longer duration in women, more studies are required to delineate the role of biological sex. Factors that influence CBD PK have implications for medication development and appropriate dosing in clinical practice.
在这篇综述中，我们提供了对 CBD 药代动力学（PK）现有证据的最新评估，并探讨了不同因素对 PK 结果的影响。本系统评价和荟萃回归分析已预先注册（PROSPERO：CRD42021269857）。我们系统地检索了 Medline、Embase、PsycInfo 和 Web of Science Core Collection，截至 2022 年 11 月 19 日。如果试验报告了血清或血浆中至少一个感兴趣的 PK 参数，包括 T、C、AUC、AUC 和 T，则纳入健康成年人中 CBD 的试验。排除了患者人群或 CBD 与其他药物联合用药的研究。使用了偏倚风险评估工具（ROB）。进行了随机效应多变量荟萃回归分析。共纳入 39 项研究的 112 个试验臂；26 个试验臂质量为“良好”，70 个为“中等”，16 个为“差”。8 个试验臂使用吸入 CBD，29 个口腔黏膜给药，73 个口服，2 个静脉内给药。CBD 制剂可分为纳米技术（=14）、油基（=21）、酒精基（=10）、水基（=12）、Sativex（=17）和 Epidiolex（=22）。对于单剂量研究，吸入 CBD 剂量范围为 2 至 100mg，口腔黏膜给药 5 至 50mg，口服给药 0.42 至 6000mg。66 个试验臂只有男性参与者或男性参与者多于女性参与者。PK 疗程时间为 4 至 164 小时。较高的 CBD 剂量与较高的 C、AUC 和 AUC 相关。与口服给药相比，口腔黏膜给药与较低的 C、AUC 和 AUC 相关。与禁食状态相比，进食状态与更高的 C 和 AUC 相关。与口服给药相比，女性参与者比例较高与较低的 T 和较高的 C 相关。正如预期的那样，CBD 剂量、给药途径和饮食是 CBD PK 的主要决定因素，口服途径提供更高的生物利用度，纳米技术制剂具有更快的起效时间。尽管 CBD 在女性中似乎具有更快的起效时间和更长的作用持续时间，但需要更多的研究来阐明生物性别在其中的作用。影响 CBD PK 的因素对药物开发和临床实践中的适当剂量具有重要意义。
