Heat Exposure of Cannabis sativa Extracts Affects the Pharmacokinetic and Metabolic Profile in Healthy Male Subjects
Heat Exposure of Cannabis sativa Extracts Affects the Pharmacokinetic and Metabolic Profile in Healthy Male Subjects
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DOI：
10.1055/s-0031-1298334
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发表时间：
2012-05-01
期刊：
影响因子：
2.7
通讯作者：
Drewe, Juergen
中科院分区：
文献类型：
--
作者：
Eichler, Martin;Spinedi, Luca;Drewe, Juergen
大麻最重要的精神活性成分是 Delta(9)-四氢大麻酚 (THC)。大麻二酚 (CBD) 是另一种重要成分，能够调节 THC 独特的不良精神作用。在C. sativa的天然植物提取物中，大量的THC和CBD以THCA-A（THC-acid-A）和CBDA（大麻二酚酸）的形式出现，通过加热可转化为THC和CBD。先前有关大麻或具有较高 CBD/THC 比例的大麻制剂的药用以及以其天然、未加热形式使用的报告表明，药理作用通常伴随着较低的不良反应发生率。因此，在本研究中，在一项涉及 9 名健康男性志愿者的双盲、随机、单中心、三阶段交叉研究中，将 CBD/THC 比率 > 1 的两种不同的苜蓿提取物（加热和未加热）的药代动力学和代谢特征与合成 THC（屈大麻酚）进行比较。大麻素的药代动力学变化很大。给予不同形式后，代谢模式显着不同：加热的提取物显示出比未加热的提取物更低的中位 THC 血浆 AUC（24 小时），分别为 2.84 和 6.59 pmol h/mL。后者略高于屈大麻酚(4.58 pmol h/mL)。另一方面，加热提取物的代谢物（THC、11-OH-THC、THC-COOH、CBN）血浆 AUC（24 小时）中位数总和高于未加热提取物。未加热提取物的 CBD 血浆 AUC（24 小时）中位数几乎是加热提取物的 2 倍。这些结果表明，使用未加热的提取物可能会导致代谢模式发生有益的变化，并可能带来更好的耐受性。
The most important psychoactive constituent of Cannabis sativa L. is Delta(9)-tetrahydrocannabinol (THC). Cannabidiol (CBD), another important constituent, is able to modulate the distinct unwanted psychotropic effect of THC. In natural plant extracts of C. sativa, large amounts of THC and CBD appear in the form of THCA-A (THC-acid-A) and CBDA (cannabidiolic acid), which can be transformed to THC and CBD by heating. Previous reports of medicinal use of cannabis or cannabis preparations with higher CBD/THC ratios and use in its natural, unheated form have demonstrated that pharmacological effects were often accompanied with a lower rate of adverse effects. Therefore, in the present study, the pharmacokinetics and metabolic profiles of two different C. sativa extracts (heated and unheated) with a CBD/THC ratio > 1 were compared to synthetic THC (dronabinol) in a double-blind, randomized, single center, three-period cross-over study involving 9 healthy male volunteers. The pharmacokinetics of the cannabinoids was highly variable. The metabolic pattern was significantly different after administration of the different forms: the heated extract showed a lower median THC plasma AUC(24 h) than the unheated extract of 2.84 vs. 6.59 pmol h/mL, respectively. The later was slightly higher than that of dronabinol (4.58 pmol h/mL). On the other hand, the median sum of the metabolites (THC, 11-OH-THC, THC-COOH, CBN) plasma AUC(24 h) was higher for the heated than for the unheated extract. The median CBD plasma AUC(24 h) was almost 2-fold higher for the unheated than for the heated extract. These results indicate that use of unheated extracts may lead to a beneficial change in metabolic pattern and possibly better tolerability.