Moazen-Zadeh Ehsan, Chisholm Alexandra, Bachi Keren, Hurd Yasmin L
medRxiv. 2023 Feb 2:2023.02.01.23285341. doi: 10.1101/2023.02.01.23285341.
In this review, we provide an updated assessment of available evidence on the pharmacokinetics (PK) of cannabidiol (CBD) and explore the impact of different factors on PK outcomes.
This systematic review and meta-regression analysis was pre-registered (PROSPERO: CRD42021269857). We systematically searched Medline, Embase, PsychInfo, 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 Tmax, Cmax, AUC0-t, AUC0-inf, 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 (n=14), oil-based (n=21), alcohol-based (n=10), water-based (n=12), Sativex (n=17), and Epidiolex (n=22). For single-dose studies, CBD doses ranged between 2-100mg in inhalation, 5-50mg in oromucosal, and 0.42-6000mg in oral administration. Sixty-six trial arms had only male participants or a higher number of males than females. The duration of the PK session was between 4h-164h. A higher CBD dose was associated with higher Cmax, AUC0-t, and AUC0-inf. Compared to oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf. Fed status was associated with higher Cmax and AUC0-t when compared to the fasting status. A higher ratio of female participants was associated with lower Tmax in oral administration and higher Cmax.
As expected, CBD dose, route of administration, and diet were major determinants of CBD pharmacokinetics with oral routes providing higher bioavailability and nanotechnology formulations a faster onset. Though CBD appeared to have a faster onset and longer duration in females, 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.
在本综述中，我们对大麻二酚（CBD）药代动力学（PK）的现有证据进行了更新评估，并探讨了不同因素对PK结果的影响。
本系统综述和meta回归分析已预先注册（PROSPERO：CRD42021269857）。我们系统检索了截至2022年11月19日的Medline、Embase、PsychInfo和Web of Science核心合集。纳入健康成年人中CBD的试验，如果它们报告了血清或血浆中至少一项感兴趣的PK参数，包括达峰时间（Tmax）、峰浓度（Cmax）、零至t时间的药时曲线下面积（AUC0-t）、零至无穷大时间的药时曲线下面积（AUC0-inf）和半衰期（T1/2）。排除患者人群或CBD与其他药物联合给药的研究。采用随机效应多变量meta回归分析。
共纳入39项研究的112个试验组；26个试验组质量为“良好”，70个为“中等”，16个为“差”。8个试验组使用吸入式CBD，29个使用口腔黏膜给药，73个使用口服给药，2个使用静脉给药。CBD制剂可分为纳米技术制剂（n = 14）、油基制剂（n = 21）、醇基制剂（n = 10）、水基制剂（n = 12）、萨替维克斯（n = 17）和艾伯维克斯（n = 22）。对于单剂量研究，吸入式CBD剂量范围为2 - 100mg，口腔黏膜给药为5 - 50mg，口服给药为0.42 - 6000mg。66个试验组仅纳入男性参与者或男性数量多于女性。PK试验的持续时间为4小时至164小时。较高的CBD剂量与较高的Cmax、AUC0-t和AUC0-inf相关。与口服给药相比，口腔黏膜给药与较低的Cmax、AUC0-t和AUC0-inf相关。与禁食状态相比，进食状态与较高的Cmax和AUC0-t相关。较高比例的女性参与者与口服给药时较低的Tmax和较高的Cmax相关。
正如预期的那样，CBD剂量、给药途径和饮食是CBD药代动力学的主要决定因素，口服途径具有更高的生物利用度，纳米技术制剂起效更快。尽管CBD在女性中似乎起效更快、持续时间更长，但需要更多研究来阐明生物学性别所起的作用。影响CBD PK的因素对药物开发和临床实践中的适当给药具有重要意义。
