Effect of Piperine Codelivery on the Oral Bioavailability of Cannabidiol: Insights from In Vitro Digestion and In Vivo Pharmacokinetics

This study investigated whether coencapsulation of cannabidiol (CBD) and piperine (PIP) in food-grade nanostructured lipid carriers (NLCs) enhances the CBD oral bioavailability. NLCs containing long-chain fatty acids were formulated with 1% CBD and 1% PIP using either a CBD isolate (CBD(iso)) or a CBD extract (CBD(ext)). Both systems showed high encapsulation efficiency and good stability over 28 days, with similar physicochemical properties. However, the CBD form strongly influenced digestion…

J Agric Food Chem. 2026 Jun 17. doi: 10.1021/acs.jafc.6c02678. Online ahead of print.

ABSTRACT

This study investigated whether coencapsulation of cannabidiol (CBD) and piperine (PIP) in food-grade nanostructured lipid carriers (NLCs) enhances the CBD oral bioavailability. NLCs containing long-chain fatty acids were formulated with 1% CBD and 1% PIP using either a CBD isolate (CBDiso) or a CBD extract (CBDext). Both systems showed high encapsulation efficiency and good stability over 28 days, with similar physicochemical properties. However, the CBD form strongly influenced digestion behavior: NLC-PIP-CBDiso exhibited high bioaccessibility for CBD (87 ± 5%), while NLC-PIP-CBDext showed markedly lower values (13 ± 4%). Based on these results, NLC-PIP-CBDiso was evaluated in a mouse pharmacokinetic study against NLC-CBDiso and CBD in hemp seed oil. While NLC-CBDiso did not improve absorption, NLC-PIP-CBDiso doubled the CBD systemic exposure, confirming that PIP codelivery significantly enhanced oral CBD absorption.

PMID:42311044 | DOI:10.1021/acs.jafc.6c02678