Quantifying Heart Rate Changes After Delta-9-Tetrahydrocannabinol Administration Using a PBPK-PD Model in Healthy Adults.

ABSTRACT: Background: As cannabis becomes legal in several U.S. states, the risk of THC-induced tachycardia increases. This study aimed to develop and verify a physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) model to assess the impact of THC and its active metabolite, 11-hydroxy-THC (11-OH-THC), on the heart rate of healthy adults. Methods: A PBPK-PD model for intravenous (IV) 11-OH-THC administration was first developed. Secondly, a PBPK-PD model for IV THC, combined with the metabolized 11-OH-THC, was established, verified, and validated. Direct PD models driven by the plasma, brain, and heart concentrations of THC and 11-OH-THC predicted using our previously verified PBPK model were tested for model development. Finally, the risks of tachycardia at a rest condition f

SUBMITTER: Qian L 

PROVIDER: S-EPMC11858910 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature