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Inhibition of Nicotine Metabolism by Cannabidiol (CBD) and 7-Hydroxycannabidiol (7-OH-CBD)

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Cannabis-based products have experienced notable increases in co-usage alongside tobacco products. Several cannabinoids exhibit inhibition of a number of cytochrome P450 (CYP) and UDP glucuronosyltransferase (UGT) enzymes, but few studies have examined their inhibition of enzymes involved in nicotine metabolism. The goal of the present study was to examine potential drug–drug interactions occurring in the nicotine metabolism pathway perpetrated by cannabidiol (CBD) and its active metabolite, 7-hydroxy-CBD (7-OH-CBD). The inhibitory effects of CBD and 7-OH-CBD were tested in microsomes from HEK293 cells overexpressing individual metabolizing enzymes and from human liver tissue. Assays with overexpressing microsomes demonstrated that CBD and 7-OH-CBD inhibited CYP-mediated nicotine metabolism.

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Endocannabinoid signaling in glioma

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High-grade gliomas constitute the most frequent and aggressive form of primary brain cancer in adults. These tumors express cannabinoid CB1 and CB2 receptors, as well as other elements of the endocannabinoid system. Accruing preclinical evidence supports that pharmacological activation of cannabinoid receptors located on glioma cells exerts overt anti-tumoral effects by modulating key intracellular signaling path- ways. The mechanism of this cannabinoid receptor-evoked anti-tumoral activity in experimental models of glioma is intricate and may involve an inhibition not only of cancer cell survival/proliferation, but also of invasiveness, angiogenesis, and the stem cell-like properties of cancer cells, thereby affecting the complex tumor microenvi- ronment. However, the precise biological role of the endocannabinoid system in the generation and progression of glioma seems very context-dependent and remains largely unknown. Increasing our basic knowledge on how (endo)cannabinoids act on glioma cells could help to optimize experimental cannabinoid-based anti-tumoral therapies, as well as the preliminary clinical testing that is currently underway.

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