TABLE 4

Prediction of the maximum magnitude of a drug interaction when CBD or THC is administered orally or by inhalation (THC only) with the indicated object drug based on the ability of the cannabinoids to inhibit CYPs in a time-dependent and/or reversible manner

PrecipitantCYP EnzymeObject DrugPredicted AUCR after Oral Administration (Inhibition of Hepatic and Gut Metabolism)Predicted AUCR after Inhalation (Inhibition of Hepatic Metabolism)
Iinlet,max,uaImax,u and Iinlet,max,ubImax,uc
CBD (70 mg, oral)1A2Theophylline3.93.0–
2C9Diclofenac2.62.6–
2C19Omeprazole6.21.9–
2D6Dextromethorphan1.11.1–
3AMidazolam13.54.4–
CBD (700 mg, oral)1A2Theophylline4.03.9–
2C9Diclofenac11.111.1–
2C19Omeprazole7.56.4–
2D6Dextromethorphan2.32.3–
3AMidazolam15.013.4–
CBD (2000 mg, oral)1A2Theophylline4.04.0–
2C9Diclofenac23.623.6–
2C19Omeprazole7.67.4–
2D6Dextromethorphan4.84.8–
3AMidazolam15.114.8–
THC (20 mg, oral)1A2Theophylline1.1─–
2C9Diclofenac2.2─–
2C19Omeprazole1.0─–
2D6Dextromethorphan1.0─–
3AMidazolam1.8─–
THC (130 mg, oral)1A2Theophylline1.4─–
2C9Diclofenac5.6─–
2C19Omeprazole1.1─–
2D6Dextromethorphan1.0─–
3AMidazolam1.8─–
THC (160 mg, oral)1A2Theophylline1.4─–
2C9Diclofenac6.5─–
2C19Omeprazole1.1─–
2D6Dextromethorphan1.0─–
3AMidazolam1.8─–
THC (25 mg, inhaled)1A2Theophylline–─1.0
2C9Diclofenac–─1.9
2C19Omeprazole–─1.0
2D6Dextromethorphan–─1.0
3AMidazolam–─1.8
THC (70 mg, inhaled)1A2Theophylline–─1.1
2C9Diclofenac–─2.5
2C19Omeprazole–─1.0
2D6Dextromethorphan–─1.0
3AMidazolam–─1.8
THC (100 mg, inhaled)1A2Theophylline–─1.1
2C9Diclofenac–─2.9
2C19Omeprazole–─1.0
2D6Dextromethorphan–─1.0
3AMidazolam–─1.8

  • ─, time-dependent inhibition was not evident; –, not predicted.

  • ↵a Estimated unbound plasma concentration of inhibitor/inactivator in portal vein.

  • ↵b Imax,u for inactivation and Iinlet,max,u for reversible inhibition.

  • ↵c Unbound systemic plasma concentration of inhibitor/inactivator.