Aims: Cannabidiol (CBD), one of the major constituents in marijuana, has been shown to be extensively metabolized by experimental animals and humans. However, human hepatic enzymes responsible for the CBD metabolism remain to be elucidated. In this study, we examined in vitro metabolism of CBD with human liver microsomes (HLMs) to clarify cytochrome P450 (CYP) isoforms involved in the CBD oxidations. Main methods: Oxidations of CBD in HLMs and recombinant human CYP enzymes were analyzed by gas chromatography/mass spectrometry. Key findings: CBD was metabolized by pooled HLMs to eight monohydroxylated metabolites (6α-OH-, 6β-OH-, 7-OH-, 1″-OH-, 2″-OH-, 3″-OH-, 4″-OH-, and 5″-OH-CBDs). Among these metabolites, 6α-OH-,...

Increasing interest in the biology, chemistry, pharmacology, and toxicology of cannabinoids and in the development of cannabinoid medications necessitates an understanding of cannabinoid pharmacokinetics and disposition into biological fluids and tissues. A drug's pharmacokinetics determines the onset, magnitude, and duration of its pharmacodynamic effects. This review of cannabinoid pharmacokinetics encompasses absorption following diverse routes of administration and from different drug formulations, distribution of analytes throughout the body, metabolism by different tissues and organs, elimination from the body in the feces, urine, sweat, oral fluid, and hair, and how these processes change over time. Cannabinoid pharmacokinetic research has been especially challenging due to low analyte...