Chesney Edward, Mazibuko Ndabezinhle, Oliver Dominic, Minichino Amedeo, Lamper Ayşe Doğa, Chester Lucy, Reilly Thomas J, Lloyd Millie, Kråkström Matilda, Dickens Alex M, Orešič Matej, Lynch Eric, Stoloff Gregory, Mehta Mitul A, McGuire Philip
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AB, UK.
National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
Pharmaceutics. 2024 Dec 1;16(12):1537. doi: 10.3390/pharmaceutics16121537.
: Cannabidiol (CBD) is an approved treatment for childhood epilepsies and a candidate treatment for several other CNS disorders. However, it has poor oral bioavailability. We investigated the effect of a novel lipid formulation on its absorption in humans and on its tissue distribution in mice. : In a double-blind crossover study in fasting healthy volunteers, we compared the pharmacokinetics of a single dose of 1000 mg of CBD in the lipid formulation and in a powder formulation (ClinicalTrials.gov: NCT05032807). In a second study, male CD1 mice were administered CBD in either the lipid formulation or dissolved in water, via oral gavage (n = 1 per timepoint). The tissue distribution of CBD was assessed using matrix-assisted laser desorption/ionization mass spectrometric imaging. : Plasma exposure (AUC) of CBD was nine times greater for the lipid formulation than the powder formulation (611.1 ng·h/mL [coefficient of variation {CV%}: 104.6] and 66.8 ng·h/mL [CV%: 50.7], respectively). With the powder formulation, the AUC was related to the concentration of specific gastrointestinal bacteria and bile acids. These associations were attenuated with the lipid formulation. In the animal study, after treatment with the lipid formulation, measurable concentrations of CBD were identified in all organs. For the aqueous formulation, tissue concentrations of CBD were below the limit of quantification. : Administering oral CBD in a lipid formulation was associated with an increase in its gastrointestinal absorption, as well as an attenuation of the relationship between its absorption and features of the gut microbiome.
大麻二酚（CBD）是一种已获批准用于治疗儿童癫痫的药物，也是其他几种中枢神经系统疾病的候选治疗药物。然而，它的口服生物利用度较差。我们研究了一种新型脂质制剂对其在人体中的吸收以及在小鼠体内组织分布的影响。
在一项针对空腹健康志愿者的双盲交叉研究中，我们比较了单次服用1000毫克脂质制剂和粉末制剂中CBD的药代动力学（ClinicalTrials.gov：NCT05032807）。在第二项研究中，通过口服灌胃给雄性CD1小鼠施用脂质制剂或溶于水的CBD（每个时间点n = 1）。使用基质辅助激光解吸/电离质谱成像评估CBD的组织分布。
脂质制剂中CBD的血浆暴露量（AUC）比粉末制剂高九倍（分别为611.1纳克·小时/毫升[变异系数{CV%}：104.6]和66.8纳克·小时/毫升[CV%：50.7]）。对于粉末制剂，AUC与特定胃肠道细菌和胆汁酸的浓度有关。这些关联在脂质制剂中减弱。在动物研究中，用脂质制剂治疗后，在所有器官中都检测到了可测量浓度的CBD。对于水性制剂，CBD的组织浓度低于定量限。
口服脂质制剂的CBD与其胃肠道吸收增加有关，同时也减弱了其吸收与肠道微生物群特征之间的关系。
