TABLE 1.

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

Probe Substrate	Microsomal Protein	THC		11-OH-THC		THC-COO-Gluc		CBD		CBN
		IC 50 a	IC 50,u a , b	IC 50	IC 50,u	IC 50	IC 50,u	IC 50	IC 50,u	IC 50	IC 50,u
Phenacetin	rCYP1A2	2.7 ± 1.2	0.12 ± 0.052		NAc		NA	2.1 ± 0.93	0.13 ± 0.058		NA
	HLM	5.2 ± 2.1	0.27 ± 0.11		NA		NA	6.8 ± 1.5	0.67 ± 0.15		NA
Midazolam	rCYP3A4		NA		NA		NA	3.0 ± 0.52	0.19 ± 0.032		NA
	HLM		NA		NA		NA	4.6 ± 1.3	0.45 ± 0.13		NA
Bupropion	rCYP2B6	10 ± 6.4	0.43 ± 0.28	7.1 ± 3.3	0.55 ± 0.26	5.5 ± 1.6	2.5 ± 0.72	2.1 ± 0.61	0.13 ± 0.038	2.1 ± 0.87	0.63 ± 0.26
	HLM	19 ± 2.3	0.97 ± 0.12	8.2 ± 3.7	0.77 ± 0.35	5.3 ± 2.4	2.3 ± 1.0	2.7 ± 2.4	0.26 ± 0.24	1.7 ± 0.59	0.88 ± 0.31
Diclofenac	rCYP2C9	4.5 ± 3.0	0.19 ± 0.13	3.8 ± 1.1	0.30 ± 0.086	15 ± 4.5	6.8 ± 2.0	3.6 ± 1.6	0.22 ± 0.099	1.4 ± 0.44	0.42 ± 0.13
	HLM	7.2 ± 2.6	0.37 ± 0.13	4.8 ± 2.6	0.45 ± 0.24	18 ± 2.5	7.7 ± 1.1	4.9 ± 1.6	0.48 ± 0.16	2.9 ± 0.51	1.51 ± 0.27
Omeprazole	rCYP2C19	3.6 ± 0.70	0.15 ± 0.030		NA		NA	2.5 ± .50	0.16 ± 0.031		NA
	HLM	4.2 ± 1.1	0.21 ± 0.056		NA		NA	3.7 ± 1.5	0.36 ± 0.15		NA
Dextromethorphan	rCYP2D6	11 ± 1.8	0.47 ± 0.077	4.3 ± 1.5	0.34 ± 0.12	7.8 ± 1.6	3.5 ± 0.72	3.1 ± 0.64	0.19 ± 0.040		NA
	HLM	15 ± 5.3	0.77 ± 0.27	6.5 ± 3.4	0.61 ± 0.32	13 ± 3.6	5.6 ± 1.5	5.3 ± 1.0	0.52 ± 0.10		NA
Chlorzoxazone	rCYP2E1		NA		NA		NA	0.59 ± 0.13	0.037 ± 0.0081	0.92 ± 0.10	0.28 ± 0.030
	HLM		NA		NA		NA	1.4 ± 0.25	0.14 ± 0.025	1.1 ± 0.72	0.57 ± 0.37

^aValues are the mean ± S.D. in µM for four independent experiments with three replicates per group.

^bIC_50,u values represent IC₅₀ values after correction for unbound fraction (f_u,inc) of individual cannabinoids as described in Materials and Methods.

^cNA, not analyzed.