Figure 3. JWH-018 and M1–M5 activate CB1R.

A. Ten µM concentrations of JWH-018, M1, M2, M3, and M5 activated brain GPCRs greater than 10 µM Δ⁹-THC. Activation by JWH-018, M2, M3 and M5 did not differ from the full CB1R agonist CP-55,940. Values designated with different letters above the error bars are significantly different (P<0.05, one way ANOVA with Tukey's Multiple Comparison post-hoc Test, n = 3–10). B. JWH-018 and M1 stimulated G-proteins more potently and efficaciously than Δ⁹-THC, n = 3–4. C. GPCR activation by an estimated ED₉₀ concentration (100 nM) of metabolites was blocked by co-incubation with 1 µM of the selective neutral CB1R antagonist O-2050 (**P<0.01, ***P<0.001 vs drug alone, Student's t-test, n = 3–7).