TABLE 1

IC50 values of cannabinoids and THC metabolites against major hepatic CYP450 enzymes in microsomes from recombinant CYP450-overexpressing cells or HLMs

Probe SubstrateMicrosomal ProteinTHC11-OH-THCTHC-COO-GlucCBDCBN
IC50aIC50,ua,bIC50IC50,uIC50IC50,uIC50IC50,uIC50IC50,u
PhenacetinrCYP1A22.7 ± 1.20.12 ± 0.052NAcNA2.1 ± 0.930.13 ± 0.058NA
HLM5.2 ± 2.10.27 ± 0.11NANA6.8 ± 1.50.67 ± 0.15NA
MidazolamrCYP3A4NANANA3.0 ± 0.520.19 ± 0.032NA
HLMNANANA4.6 ± 1.30.45 ± 0.13NA
BupropionrCYP2B610 ± 6.40.43 ± 0.287.1 ± 3.30.55 ± 0.265.5 ± 1.62.5 ± 0.722.1 ± 0.610.13 ± 0.0382.1 ± 0.870.63 ± 0.26
HLM19 ± 2.30.97 ± 0.128.2 ± 3.70.77 ± 0.355.3 ± 2.42.3 ± 1.02.7 ± 2.40.26 ± 0.241.7 ± 0.590.88 ± 0.31
DiclofenacrCYP2C94.5 ± 3.00.19 ± 0.133.8 ± 1.10.30 ± 0.08615 ± 4.56.8 ± 2.03.6 ± 1.60.22 ± 0.0991.4 ± 0.440.42 ± 0.13
HLM7.2 ± 2.60.37 ± 0.134.8 ± 2.60.45 ± 0.2418 ± 2.57.7 ± 1.14.9 ± 1.60.48 ± 0.162.9 ± 0.511.51 ± 0.27
OmeprazolerCYP2C193.6 ± 0.700.15 ± 0.030NANA2.5 ± .500.16 ± 0.031NA
HLM4.2 ± 1.10.21 ± 0.056NANA3.7 ± 1.50.36 ± 0.15NA
DextromethorphanrCYP2D611 ± 1.80.47 ± 0.0774.3 ± 1.50.34 ± 0.127.8 ± 1.63.5 ± 0.723.1 ± 0.640.19 ± 0.040NA
HLM15 ± 5.30.77 ± 0.276.5 ± 3.40.61 ± 0.3213 ± 3.65.6 ± 1.55.3 ± 1.00.52 ± 0.10NA
ChlorzoxazonerCYP2E1NANANA0.59 ± 0.130.037 ± 0.00810.92 ± 0.100.28 ± 0.030
HLMNANANA1.4 ± 0.250.14 ± 0.0251.1 ± 0.720.57 ± 0.37
  • aValues are the mean ± S.D. in µM for four independent experiments with three replicates per group.

  • bIC50,u values represent IC50 values after correction for unbound fraction (fu,inc) of individual cannabinoids as described in Materials and Methods.

  • cNA, not analyzed.