Lambert Initiative for Cannabinoid Therapeutics, Brain and Mind Centre , The University of Sydney , Sydney , New South Wales 2050 , Australia.
Discipline of Pharmacology, Faculty of Medicine and Health , The University of Sydney , Sydney , New South Wales 2006 , Australia.
J Nat Prod. 2019 Nov 22;82(11):3047-3055. doi: 10.1021/acs.jnatprod.9b00600. Epub 2019 Nov 5.
produces a complex mixture of many bioactive molecules including terpenophenolic compounds known as phytocannabinoids. Phytocannabinoids come in neutral forms (e.g., Δ-tetrahydrocannabinol, THC; cannabidiol, CBD; etc.) or as acid precursors, which are dominant in the plant (e.g., Δ-tetrahydrocannabinolic acid, THCA; cannabidiolic acid, CBDA; etc.). There is increasing interest in unlocking the therapeutic applications of the phytocannabinoid acids; however, the present understanding of the basic pharmacology of phytocannabinoid acids is limited. Herein the brain and plasma pharmacokinetic profiles of CBDA, THCA, cannabichromenic acid (CBCA), cannabidivarinic acid (CBDVA), cannabigerolic acid (CBGA), and cannabigerovarinic acid (CBGVA) were examined following intraperitoneal administration in mice. Next it was examined whether CBDA was anticonvulsant in a mouse model of Dravet syndrome ( mice). All the phytocannabinoid acids investigated were rapidly absorbed with plasma values of between 15 and 45 min and had relatively short half-lives (<4 h). The brain-plasma ratios for the acids were very low at ≤0.04. However, when CBDA was administered in an alternate Tween 80-based vehicle, it exhibited a brain-plasma ratio of 1.9. The anticonvulsant potential of CBDA was examined using this vehicle, and it was found that CBDA significantly increased the temperature threshold at which the mice had a generalized tonic-clonic seizure.
产生了许多生物活性分子的复杂混合物，包括被称为植物大麻素的萜酚类化合物。植物大麻素以中性形式（例如 Δ-四氢大麻酚，THC；大麻二酚，CBD；等）或作为酸前体存在，这些酸前体在植物中占主导地位（例如 Δ-四氢大麻酸，THCA；大麻二酚酸，CBDA；等）。人们对开发植物大麻素酸的治疗应用越来越感兴趣；然而，目前对植物大麻素酸的基本药理学的理解有限。本文研究了 CBDA、THCA、大麻色胺酸（CBCA）、大麻二酚酸（CBDVA）、大麻二醇酸（CBGA）和大麻二醇酸（CBGVA）在腹腔给药后在小鼠中的脑和血浆药代动力学特征。接下来，研究了 CBDA 是否在 Dravet 综合征（Scn1a+/− 小鼠）的小鼠模型中具有抗惊厥作用。所有研究的植物大麻素酸均被迅速吸收，血浆 值在 15 至 45 分钟之间，半衰期较短（<4 小时）。酸的脑-血浆比值非常低，≤0.04。然而，当 CBDA 以替代的 Tween 80 为基础的载体给药时，它表现出 1.9 的脑-血浆比值。使用这种载体研究了 CBDA 的抗惊厥潜力，发现 CBDA 显著提高了 小鼠发生全身性强直-阵挛性癫痫的温度阈值。
