Population Pharmacokinetics of Oral-Based Administration of Cannabidiol in Healthy Adults: Implications for Drug Development

Cannabidiol (CBD) is increasingly studied as a therapeutic option, but its pharmacokinetics remain incompletely understood, complicating oral dose-form development. This study used a population pharmacokinetic approach, based on a four-way crossover Phase I trial in 12 healthy adults, to characterize CBD pharmacokinetics with Monte Carlo simulations of chronic twice-daily dosing performed using Phoenix NLME. A three-compartment model with transit absorption compartments best described CBD disposition, revealing substantial inter-individual variability (up to 60% CV) not explained by measured covariates, along with a 3.6-fold difference in steady-state exposure and up to three weeks’ variability in time to reach steady state. These findings indicate that a one-size-fits-all CBD dosing approach may not be feasible given the large observed pharmacokinetic variability, with implications for future trial design.