Effect of preincubation on inhibition of P450 activity by cannabinoids and THC metabolites in microsomes from CYP450-overexpressing cell lines
| THC | 11-OH-THC | THC-COO-Gluc | CBD | CBN | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Enzyme | (−)a | (+)b | Shiftc | (−) | (+) | Shift | (−) | (+) | Shift | (−) | (+) | Shift | (−) | (+) | Shift |
| CYP1A2 | 2.7 ± 1.0 | 1.8 ± 0.55 | 1.4 ± 0.12 | NAd | NA | 2.1 ± 0.25 | 1.8 ± 0.31 | 1.2 ± 0.20 | NA | ||||||
| CYP3A4 | NA | NA | NA | 3.1 ± 1.2 | 2.0 ± 1.1 | 1.1 ± 0.077 | NA | ||||||||
| CYP2B6 | 19 ± 5.1 | 18 ± 5.0 | 1.1 ± 0.049 | 7.3 ± 1.0 | 6.1 ± 1.0 | 1.2 ± 0.094 | 5.1 ± 1.6 | 4.1 ± 1.0 | 1.4 ± 0.16 | 1.9 ± 0.66 | 1.3 ± 0.45 | 1.3 ± 0.048 | 2.1 ± 0.83 | 2.0 ± 0.70 | 1.1 ± 0.061 |
| CYP2C9 | 3.4 ± 2.3 | 2.3 ± 1.7 | 1.4 ± 0.17 | 3.2 ± 0.61 | 2.2 ± 0.59 | 1.4 ± 0.18 | 15 ± 2.4 | 15 ± 2.7 | 1.0 ± 0.044 | 2.2 ± 1.2 | 1.8 ± 0.85 | 1.2 ± 0.12 | 3.0 ± 2.2 | 2.7 ± 2.1 | 1.1 ± 0.11 |
| CYP2C19 | 3.2 ± 2.5 | 2.5 ± 1.8 | 1.3 ± 0.13 | NA | NA | 2.5 ± 1.5 | 2.3 ± 1.3 | 1.1 ± 0.074 | NA | ||||||
| CYP2D6 | 13 ± 0.67 | 10 ± 0.92 | 1.3 ± 0.068 | 2.9 ± 0.86 | 2.1 ± 0.49 | 1.3 ± 0.14 | 8.1 ± 1.1 | 6.4 ± 2.5 | 1.4 ± 0.51 | 2.9 ± 1.1 | 2.0 ± 0.76 | 1.5 ± 0.33 | NA | ||
| CYP2E1 | NA | NA | NA | 1.1 ± 0.66 | 0.9 ± 0.40 | 1.2 ± 0.20 | 0.87 ± 0.15 | 0.73 ± 0.21 | 1.2 ± 0.16 | ||||||
↵a(−), IC50 ± S.D. (µM) value of three experiments with 30-min preincubation of test cannabinoid with enzyme without NADPH.
↵b(+), IC50 ± S.D. (µM) value of three experiments with 30-min preincubation of test cannabinoid with enzyme and NADPH.
↵cShift = (IC50 “minus NADPH”/IC50 “plus NADPH”) ± S.D. of three experiments.
↵dNA, not analyzed.