Assessment of intestinal absorption of five cannabinoids from an ethanolic CBD-rich hemp extract using Caco-2 cells in vitro

Cannabinoids are highly lipophilic constituents of the hemp plant, which is present in several products intended for consumption. While cannabidiol (CBD) effects to humans have been extensively investigated, there is limited information on other minor cannabinoids. CBD oral bioavailability is low but increases with food and high-fat intake. We used Caco-2 cells in vitro to assess intestinal absorption of five cannabinoids (CBD, CBC, CBG, CBN, and CBDV) present in a CBD-rich hemp extract. We used a fed-state simulated intestinal fluid (Fessif) for dissolution of cannabinoids. Cannabinoids did not alter Caco-2 monolayer integrity. Except for CBC, recovery of cannabinoids decreased significantly after 90-minute incubation, compared to 60-minute incubation. No measurable cannabinoids were identified in the bottom chambers. Recovery of CBD, CBC, CBG and CBN after incubation with hemp extract or cannabinoid mix containing 30 μM CBD was unchanged, but CBDV recovery decreased. With hemp extract or a mix containing 10 μM CBD, recovery of CBD and CBC did not change, CBG recovery was lower (80-82 %), and CBN and CBDV were unquantifiable. This study highlights the challenges of evaluating permeability of cannabinoids by Caco-2 cells to predict intestinal absorption, including the physicochemical properties of these compounds, incubation time and cell properties.