Δ8-THC-treated mice display tolerance and cross-tolerance to WIN 55,212-2. Mice were treated repeatedly with Δ8-THC (50 mg/kg, s.c.) for 5 days and tested daily for catalepsy (A) antinociception (B), and hypothermia (C). On day 7, all mice received WIN 55,212-2 (10 mg/kg, s.c.). Δ8-THC-treated mice displayed cross-tolerance to WIN 55,212-2-induced catalepsy (D) antinociception (E), hypothermia (F), and immobility (G). Dashed line indicates baseline body temperature. Data represent mean±SEM (n = 10[5m/5f]/group); *p<0.05, **p<0.005, ***p<0.0005, ****p<0.00005 v. vehicle; #p<0.05 v. day 1 Δ8-THC.