TABLE 3

Summary of Ki values and inhibition type for major cannabinoids and THC metabolites against hepatic CYP450 enzymes

Microsomal ProteinTHC11-OH-THCTHC-COO-GlucCBDCBN
KiaKi,uaTbKiKi,uTKiKi,uTKiKi,uTKiKi,uT
rCYP1A2c2.1 ± 0.620.090 ± 0.027CNAdNA1.9 ±1.20.12 ± 0.074MNA
HLM2.0 ± 1.10.10 ± 0.056C2.1 ± 1.10.21 ± 0.11M
rCYP3A4NANANA1.5 ± 0.590.093 ± 0.037CNA
HLM2.2 ± 0.450.22 ± 0.044C
rCYP2B65.7 ± 1.00.25 ± 0.043C1.1 ± 0.850.086 ± 0.066C2.0 ± 1.20.90 ± 0.54C1.1 ± 0.240.068 ± 0.015C0.62 ± 0.190.19 ± 0.057C
HLM7.5 ± 0.560.38 ± 0.029C2.8 ± 0.440.26 ± 0.041C2.6 ± 1.11.1 ± 0.47C2.2 ± 0.530.22 ± 0.052C1.7 ± 0.420.88 ± 0.22C
rCYP2C91.7 ± 0.530.073 ± 0.023C0.73 ± 0.560.057 ± 0.044C4.7 ± 1.82.1 ± 0.81C1.5 ± 0.570.093 ± 0.035C1.0 ± 0.190.30 ± 0.057C
HLM3.4 ± 0.910.17 ± 0.046M2.2 ± 0.340.21 ± 0.032C7.8 ± 0.653.4 ± 0.28M1.9 ± 0.150.19 ± 0.015C1.9 ± 1.30.99 ± 0.68C
rCYP2C191.3 ± 0.420.056 ± 0.018MNANA0.81 ± 0.0920.050 ± 0.0057CNA
HLM4.1 ± 1.60.21 ± 0.082M0.94 ± 0.0630.092 ± 0.0062M
rCYP2D62.5 ± 0.350.11 ± 0.015C1.9 ± 0.860.15 ± 0.067C5.0 ± 1.22.3 ± 0.54C1.2 ± 0.770.074 ± 0.048CNA
HLM5.4 ± 0.580.28 ± 0.030C3.4 ± 2.50.32 ± 0.24C6.2 ± 1.72.7 ± 0.73C3.2 ± 1.40.31 ± 0.14C
rCYP2E1NANANA0.34 ± 0.0980.021 ± 0.0061C0.21 ± 0.0970.063 ± 0.029C
HLM0.59 ± 0.230.058 ± 0.023C0.33 ± 0.0910.17 ± 0.047C
  • a,bValues are expressed as µM; shown are the mean ± S.D. for three independent experiments performed for the inhibition of each CYP450 enzyme by each cannabinoid.

  • bT, type of inhibition. C, competitive inhibition; M, mixed inhibition.

  • cThe probe substrate used were phenacetin, midazolam, bupropion, diclofenac, omeprazole, dextromethorphan, and chlorzoxazone for CYP1A2, CYP3A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, respectively.

  • dNA, not analyzed.