Cannabidiol(CBD): CYP2C19 Inhibitor for Intractable Epilepsy & Precision Oncology

Empirical studies have confirmed that cannabidiol (CBD) potently inhibits the enzymatic activity of human cytochrome P450 2C19 (CYP2C19).¹

Figure 1. CBD

Cannabidiol (CBD) has been demonstrated in multiple studies to inhibit cytochrome P450 2C19 (CYP2C19) through competitive or non-competitive mechanisms, thereby impairing the enzyme's catalytic activity. This inhibition significantly compromises the efficacy and safety of therapeutics metabolized via this enzymatic pathway.

Therapeutically leveraged inhibition of CYP2C19 by cannabidiol (CBD) offers significant translational potential through:

1.Targeted prodrug enhancement​​—delaying metabolic activation of clobazam (60% ↑ active metabolite AUC) to improve refractory epilepsy control;

2.Metabolic homeostasis modulation​​—mitigating neurotoxicity via suppression of pro-oxidant CYP2C19 metabolites (↓45% neuronal apoptosis in vivo);

3.Precision pharmacotherapy​​—strategically inducing functional CYP2C19 poor metabolizer phenotypes to optimize narrow-therapeutic-index drugs (e.g., tamoxifen sensitivity ↑2.3-fold). Key applications require genotype-guided dosing and therapeutic drug monitoring to maximize efficacy while mitigating interaction risks.

Reference

1.Rongrong Jiang et al. Cannabidiol is a potent inhibitor of the catalytic activity of cytochrome P450 2C19. Drug Metab Pharmacokinet. 2013;28(4):332-8.doi: 10.2133/dmpk.dmpk-12-rg-129. Epub 2013 Jan 15.