TABLE 3.

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

Microsomal Protein	THC			11-OH-THC			THC-COO-Gluc			CBD			CBN
	Kia	Ki,ua	Tb	K i	K i,u	T	K i	K i,u	T	K i	K i,u	T	K i	K i,u	T
rCYP1A2c	2.1 ± 0.62	0.090 ± 0.027	C		NAd			NA		1.9 ±1.2	0.12 ± 0.074	M		NA
HLM	2.0 ± 1.1	0.10 ± 0.056	C							2.1 ± 1.1	0.21 ± 0.11	M
rCYP3A4		NA			NA			NA		1.5 ± 0.59	0.093 ± 0.037	C		NA
HLM										2.2 ± 0.45	0.22 ± 0.044	C
rCYP2B6	5.7 ± 1.0	0.25 ± 0.043	C	1.1 ± 0.85	0.086 ± 0.066	C	2.0 ± 1.2	0.90 ± 0.54	C	1.1 ± 0.24	0.068 ± 0.015	C	0.62 ± 0.19	0.19 ± 0.057	C
HLM	7.5 ± 0.56	0.38 ± 0.029	C	2.8 ± 0.44	0.26 ± 0.041	C	2.6 ± 1.1	1.1 ± 0.47	C	2.2 ± 0.53	0.22 ± 0.052	C	1.7 ± 0.42	0.88 ± 0.22	C
rCYP2C9	1.7 ± 0.53	0.073 ± 0.023	C	0.73 ± 0.56	0.057 ± 0.044	C	4.7 ± 1.8	2.1 ± 0.81	C	1.5 ± 0.57	0.093 ± 0.035	C	1.0 ± 0.19	0.30 ± 0.057	C
HLM	3.4 ± 0.91	0.17 ± 0.046	M	2.2 ± 0.34	0.21 ± 0.032	C	7.8 ± 0.65	3.4 ± 0.28	M	1.9 ± 0.15	0.19 ± 0.015	C	1.9 ± 1.3	0.99 ± 0.68	C
rCYP2C19	1.3 ± 0.42	0.056 ± 0.018	M		NA			NA		0.81 ± 0.092	0.050 ± 0.0057	C		NA
HLM	4.1 ± 1.6	0.21 ± 0.082	M							0.94 ± 0.063	0.092 ± 0.0062	M
rCYP2D6	2.5 ± 0.35	0.11 ± 0.015	C	1.9 ± 0.86	0.15 ± 0.067	C	5.0 ± 1.2	2.3 ± 0.54	C	1.2 ± 0.77	0.074 ± 0.048	C		NA
HLM	5.4 ± 0.58	0.28 ± 0.030	C	3.4 ± 2.5	0.32 ± 0.24	C	6.2 ± 1.7	2.7 ± 0.73	C	3.2 ± 1.4	0.31 ± 0.14	C
rCYP2E1		NA			NA			NA		0.34 ± 0.098	0.021 ± 0.0061	C	0.21 ± 0.097	0.063 ± 0.029	C
HLM										0.59 ± 0.23	0.058 ± 0.023	C	0.33 ± 0.091	0.17 ± 0.047	C

^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.