TABLE 1

Oral and inhalational doses and estimated maximum plasma concentrations of CBD, THC, and THC metabolites used for predicting the magnitude of pharmacokinetic cannabinoid-drug interactions

CannabinoidCBD or THC Dose (mg)Route of Administration[I]max,u (nM)a[I]inlet,max,u (µM)b
CBD70Oral2.940.12
700Oral29.41.24
2000Oral84.03.55
THC20Oral0.330.01
130Oral2.150.03
160Oral2.640.04
25Inhalation2.72NA
70Inhalation7.62NA
100Inhalation10.89NA
11-OH-THC20Oral0.26
130Oral1.72
160Oral2.11
25Inhalation0.20NA
70Inhalation0.55NA
100Inhalation0.78NA
COOH-THC20Oral3.19
130Oral20.75
160Oral25.54
25Inhalation1.12NA
70Inhalation3.13NA
100Inhalation4.48NA
  • NA, not applicable; –, not estimated as data on fraction of dose metabolized to these metabolites by the intestine vs. liver are not available.

  • a fu,p (CBD) = 0.07 (Taylor et al., 2019), fu,p (THC) = 0.011 (Patilea-Vrana and Unadkat, 2019), fu,p (11-OH-THC) = 0.012 (Patilea-Vrana and Unadkat, 2019); fu,p (COOH-THC) was not available and assumed to be the same as of 11-OH-THC, and Cmax/dose of CBD and THC after oral administration or inhalation were taken from Cox et al. (2019).

  • b Fa (CBD and THC) = 1 (estimated based on FDA guidance), ka (CBD) = 0.0048 min−1 (estimated from Epidiolex (CBD) pharmacokinetic data using Phoenix WinNonlin (Phoenix WinNonlin 8.1; Certara USA, Princeton, NJ), ka (THC) = 0.0045 min−1 (Wolowich et al., 2019), QH (hepatic blood flow) = 1500 ml/min, and RB (THC) (blood to plasma ratio) = 0.4 (Schwilke et al., 2009); RB (CBD) value is not available and was assumed to be same as that for THC.