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
| Precipitant | CYP Enzyme | Object Drug | Predicted AUCR after Oral Administration (Inhibition of Hepatic and Gut Metabolism) | Predicted AUCR after Inhalation (Inhibition of Hepatic Metabolism) | |
|---|---|---|---|---|---|
| Iinlet,max,ua | Imax,u and Iinlet,max,ub | Imax,uc | |||
| CBD (70 mg, oral) | 1A2 | Theophylline | 3.9 | 3.0 | – |
| 2C9 | Diclofenac | 2.6 | 2.6 | – | |
| 2C19 | Omeprazole | 6.2 | 1.9 | – | |
| 2D6 | Dextromethorphan | 1.1 | 1.1 | – | |
| 3A | Midazolam | 13.5 | 4.4 | – | |
| CBD (700 mg, oral) | 1A2 | Theophylline | 4.0 | 3.9 | – |
| 2C9 | Diclofenac | 11.1 | 11.1 | – | |
| 2C19 | Omeprazole | 7.5 | 6.4 | – | |
| 2D6 | Dextromethorphan | 2.3 | 2.3 | – | |
| 3A | Midazolam | 15.0 | 13.4 | – | |
| CBD (2000 mg, oral) | 1A2 | Theophylline | 4.0 | 4.0 | – |
| 2C9 | Diclofenac | 23.6 | 23.6 | – | |
| 2C19 | Omeprazole | 7.6 | 7.4 | – | |
| 2D6 | Dextromethorphan | 4.8 | 4.8 | – | |
| 3A | Midazolam | 15.1 | 14.8 | – | |
| THC (20 mg, oral) | 1A2 | Theophylline | 1.1 | ─ | – |
| 2C9 | Diclofenac | 2.2 | ─ | – | |
| 2C19 | Omeprazole | 1.0 | ─ | – | |
| 2D6 | Dextromethorphan | 1.0 | ─ | – | |
| 3A | Midazolam | 1.8 | ─ | – | |
| THC (130 mg, oral) | 1A2 | Theophylline | 1.4 | ─ | – |
| 2C9 | Diclofenac | 5.6 | ─ | – | |
| 2C19 | Omeprazole | 1.1 | ─ | – | |
| 2D6 | Dextromethorphan | 1.0 | ─ | – | |
| 3A | Midazolam | 1.8 | ─ | – | |
| THC (160 mg, oral) | 1A2 | Theophylline | 1.4 | ─ | – |
| 2C9 | Diclofenac | 6.5 | ─ | – | |
| 2C19 | Omeprazole | 1.1 | ─ | – | |
| 2D6 | Dextromethorphan | 1.0 | ─ | – | |
| 3A | Midazolam | 1.8 | ─ | – | |
| THC (25 mg, inhaled) | 1A2 | Theophylline | – | ─ | 1.0 |
| 2C9 | Diclofenac | – | ─ | 1.9 | |
| 2C19 | Omeprazole | – | ─ | 1.0 | |
| 2D6 | Dextromethorphan | – | ─ | 1.0 | |
| 3A | Midazolam | – | ─ | 1.8 | |
| THC (70 mg, inhaled) | 1A2 | Theophylline | – | ─ | 1.1 |
| 2C9 | Diclofenac | – | ─ | 2.5 | |
| 2C19 | Omeprazole | – | ─ | 1.0 | |
| 2D6 | Dextromethorphan | – | ─ | 1.0 | |
| 3A | Midazolam | – | ─ | 1.8 | |
| THC (100 mg, inhaled) | 1A2 | Theophylline | – | ─ | 1.1 |
| 2C9 | Diclofenac | – | ─ | 2.9 | |
| 2C19 | Omeprazole | – | ─ | 1.0 | |
| 2D6 | Dextromethorphan | – | ─ | 1.0 | |
| 3A | Midazolam | – | ─ | 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.