Phytochemical profiling and gut microbiota interactions of Cannabis flos extracts: Insights into postbiotic metabolite formation

Cannabis sativa L. is a medicinal plant with well-documented therapeutic potential, particularly in the management of central nervous system disorders such as epilepsy, chronic pain, and nausea. Its inflorescence ( Cannabis flos , CF) contains a diverse array of specialized metabolites, including phytocannabinoids and flavonoids, that collectively account for its pharmacological activity [ 1 ]. While inhalation remains the predominant route of CF administration, oral delivery through aqueous or hydroethanolic preparations is gaining recognition as advantageous, especially for patients with pulmonary comorbidities, difficulties operating vaporization devices, or requiring prolonged and discreet therapeutic effects [ 2 ]. Recent reports underscore the critical role of the gut microbiota in modulating the pharmacokinetics, bioavailability, and efficacy of orally administered natural products. A central aspect of this interaction is the generation of postbiotic metabolites, which may exhibit enhanced or distinct biological activities relative to their precursor compounds [ 3 ] [ 4 ]. The present study aimed to characterize the phytochemical composition of Cannabis flos oral formulations, including infusions and water-ethanolic extracts prepared with or without prior plant material decarboxylation, and to investigate their interactions with human gut microbiota. Qualitative profiling and identification of postbiotic metabolites were performed using high-performance liquid chromatography coupled with diode-array detection and tandem mass spectrometry (HPLC-DAD-MS/MS). The analyses demonstrated the predominance of selected phytocannabinoids and flavonoids, emphasizing the influence of extraction conditions and thermal processing on the phytochemical profile and potential therapeutic properties of CF preparations. Furthermore, chromatographic profiling enabled the detection of several postbiotic metabolites, the biological significance of which warrants further investigation in future studies. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany