A high-fat meal significantly impacts the bioavailability and biphasic absorption of cannabidiol (CBD) from a CBD-rich extract in men and women

Cannabidiol (CBD), a specialized metabolite (phytocannabinoid) abundant in Cannabis sativa, is attracting increasing attention for its alleged health-promoting properties. The present study aimed to investigate the pharmacokinetics of CBD and its primary metabolite, 7-hydroxy-cannabidiol (7-OH-CBD), following a single oral dose of a CBD-rich Cannabis sativa extract, equivalent to 70 mg CBD, in healthy male (n=5) and female (n=6) participants. Using a randomized crossover design, the study evaluated the impact of a standardized high-fat meal compared to fasting on the oral bioavailability of CBD. Consumption of a high-fat meal significantly increases the bioavailability of CBD. The geometric mean ratio (GMR) of CBD C_max was 17.4 (90% CI 12.4-24.2 and of the AUC 9.7 (90% CI 7.7-12.3), demonstrating a substantial increase in peak concentration and total CBD exposure under fed conditions. A notable double peak phenomenon was observed after meal consumption, with a less pronounced effect in the fasted state. This contributes to sustained high plasma concentrations and may be (partially) attributed to lymphatic transport, enterohepatic recirculation, and/or a secondary meal effect.This trial was registered on October 19, 2020, with ClinicalTrials.gov under the identifier NCT04589455. The registration title is: Determination of Pharmacokinetics and Food-effect of CBD from a Hemp Extract in Healthy Human Volunteers.