Busardò Francesco Paolo, Pérez-Acevedo Ana Pilar, Pacifici Roberta, Mannocchi Giulio, Gottardi Massimo, Papaseit Esther, Pérez-Mañá Clara, Martin Soraya, Poyatos Lourdes, Pichini Simona, Farré Magí
Department of Excellence-Biomedical Sciences and Public Health, Università Politecnica delle Marche, 60121 Ancona, Italy.
Clinical Pharmacology Unit, Hospital Universitari Germans Trias i Pujol and Institut de Recerca Germans Trias i Pujol (HUGTiP-IGTP), 08916 Badalona, Spain.
Pharmaceuticals (Basel). 2021 Jan 13;14(1):59. doi: 10.3390/ph14010059.
Inhalation by vaporization is a useful application mode for medical cannabis. In this study, we present the disposition of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, and their metabolites in serum, oral fluid, and urine together with the acute pharmacological effects in 14 healthy individuals treated with vaporized medical cannabis. THC and CBD peaked firstly in serum and then in oral fluid, with higher concentrations in the first biological matrices and consequent higher area under the curve AUCs. Acidic precursors Δ-9-tetrahydrocannabinolic acid A (THCA) and cannabidiolic acid (CBDA) showed a similar time course profile but lower concentrations due to the fact that vaporization partly decarboxylated these compounds. All THC and CBD metabolites showed a later onset with respect to the parent compounds in the absorption phase and a slower decrease to baseline. In agreement with serum kinetics, THC-COOH-GLUC and 7-COOH-CBD were the significantly most excreted THC and CBD metabolites. The administration of vaporized medical cannabis induced prototypical effects associated with the administration of cannabis or THC in humans, with a kinetic trend overlapping that of parent compounds and metabolites in serum. The pharmacokinetics of cannabinoids, their precursors, and their metabolites in biological fluids of individuals treated with vaporized medical cannabis preparations showed a high interindividual variability as in the case of oral medical cannabis decoction and oil. Inhaled medical cannabis was absorbed into the organism earlier than decoction and oil. Cannabinoids reached higher systemic concentrations, also due to the fact that the acid precursors decarboxylated to parent cannabinoids at high temperatures, and consequently, the physiological and subjective effects occurred earlier and resulted with higher intensity. No serious adverse effects were observed.
通过汽化吸入是医用大麻的一种有用的应用方式。在本研究中，我们展示了14名接受汽化医用大麻治疗的健康个体中，血清、口腔液和尿液中Δ9-四氢大麻酚（THC）、大麻二酚（CBD）、它们的酸性前体及其代谢物的处置情况，以及急性药理作用。THC和CBD首先在血清中达到峰值，然后在口腔液中达到峰值，在第一种生物基质中的浓度更高，因此曲线下面积（AUC）也更高。酸性前体Δ-9-四氢大麻酚酸A（THCA）和大麻二酚酸（CBDA）显示出相似的时间进程曲线，但浓度较低，这是因为汽化使这些化合物部分脱羧。所有THC和CBD代谢物在吸收阶段相对于母体化合物出现得较晚，并且下降至基线的速度较慢。与血清动力学一致，THC-COOH-GLUC和7-COOH-CBD是排泄量显著最多的THC和CBD代谢物。汽化医用大麻的给药诱导了与人类使用大麻或THC相关的典型效应，其动力学趋势与血清中母体化合物和代谢物的趋势重叠。与口服医用大麻汤剂和油的情况一样，接受汽化医用大麻制剂治疗的个体生物流体中大麻素、其前体及其代谢物的药代动力学显示出高度的个体间变异性。吸入的医用大麻比汤剂和油更早被机体吸收。大麻素达到更高的全身浓度，这也是因为酸性前体在高温下脱羧为母体大麻素，因此生理和主观效应出现得更早且强度更高。未观察到严重不良反应。
