Phase I Hydroxylated Metabolites of the K2 Synthetic Cannabinoid JWH-018 Retain In Vitro and In Vivo Cannabinoid 1 Receptor Affinity and Activity
Figure 5
JWH-018 and M1 decreased mouse core body temperature in a CB1R-dependent manner similar to Δ9-THC.
A. Mice administered 3 mg/kg JWH-018 and 10 mg/kg M1 (i.p.) exhibited greater depressions in core body temperature than 30 mg/kg Δ9-THC, but also recovered more quickly over a 10 h time course, resulting in B. equivalent area under the curve values, which were significantly lower than vehicle controls (*P<0.005 vs. vehicle controls, one-way ANOVA with Tukey HSD test, n = 5). Core body temperature was restored to vehicle control levels by coadministration of cannabinoids with the CB1R-preferring antagonist/inverse agonist AM251 (10 mg/kg).