Figure 7. JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less fractional receptor occupancy (FRO) of CB₂Rs to produce half-maximal inhibition of AC than established cannabinoids.

The law of mass action predicts that, at equilibrium, the FRO is the proportion of all receptors that are bound by drug at a given concentration (Tallarida, 1990). FRO is calculated using the following formula: FRO = [DRUG] / (K_i + [DRUG]). Applying this concept to quantify CB₂R coupling to AC, the fractional receptor occupancy (FRO) required to produce half-maximal regulation of AC-activity was determined for the indicated cannabioids. All FRO values (mean ± SEM) are presented in Table 1.

^a,bBars identified with different letters are significantly different (P≤0.05, ANOVA + Tukey’s post-hoc test to compare all treatment combinations).