Anderson Lyndsey L, Hawkins Nicole A, Yip Ka Lai, Udoh Michael, Kearney Jennifer A, Arnold Jonathon C
Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
Discipline of Pharmacology, School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Basic Clin Pharmacol Toxicol. 2025 Jan;136(1):e14120. doi: 10.1111/bcpt.14120.
The worldwide legalization of medicinal cannabis has led to an increased use of products made by commercial operators. These products often contain minor cannabinoids such as cannabinol (CBN) which are advertised to improve sleep. Products are also available in which CBN is combined with conventional therapies, with a common product containing both CBN and the widely used sleep-aid melatonin. The combination of CBN and melatonin provides potential for a pharmacokinetic drug-drug interaction (DDI) given that cannabinoids are known to inhibit drug-metabolizing enzymes. Indeed, we recently reported that CBN potently inhibited the CYP1A2-mediated metabolism of caffeine. CYP1A2 is the major hepatic enzyme involved in the metabolism of melatonin; thus, in this study, we aimed to examine whether CBN inhibited CYP1A2-mediated metabolism of melatonin in vitro and in vivo. We found CBN potently inhibited CYP1A2-mediated metabolism of melatonin and increased the apparent oral bioavailability of melatonin in mice with a four-fold increase in the plasma melatonin exposure. Our results provide an additional example of a potential DDI involving melatonin.
药用大麻在全球范围内的合法化导致商业运营商生产的产品使用增加。这些产品通常含有诸如大麻酚（CBN）等次要大麻素，它们被宣传有助于改善睡眠。也有产品将CBN与传统疗法相结合，一种常见产品同时含有CBN和广泛使用的助眠剂褪黑素。鉴于已知大麻素会抑制药物代谢酶，CBN与褪黑素的组合存在药代动力学药物-药物相互作用（DDI）的可能性。事实上，我们最近报道CBN能有效抑制CYP1A2介导的咖啡因代谢。CYP1A2是参与褪黑素代谢的主要肝酶；因此，在本研究中，我们旨在研究CBN在体外和体内是否会抑制CYP1A2介导的褪黑素代谢。我们发现CBN能有效抑制CYP1A2介导的褪黑素代谢，并增加了小鼠体内褪黑素的表观口服生物利用度，使血浆褪黑素暴露量增加了四倍。我们的结果提供了另一个涉及褪黑素的潜在DDI的例子。
