Evaluation of side effects of analgesic doses of CB1R agonist, MOR agonist, and subanalgesic doses of CB1R-MOR agonists in combination. A, Morphine (3 mg/kg) significantly reduced oxygen saturation from 10 to 50 min after injection, while ACEA (0.3 mg/kg) or the ACEA-morphine mix (0.3 mg/kg each) had no effect (N = 5). B, ACEA significantly increased HR, while morphine significantly decreased HR, after injection; the ACEA-morphine mix had no effect (N = 5). A, B, Asterisks indicate significant differences compared with time 0. C, D, E, Morphine, ACEA, or the ACEA-morphine mix had no effect on locomotion after injection. F, Morphine significantly reduced pelleting in mice, compared with vehicle (p = 0.0104), while neither ACEA nor the ACEA-morphine mix altered pelleting over 90 min (N = 5). G, The movement patterns of mice did not differ between vehicle or treatment groups (N = 5). *p < 0.05. **p < 0.01. ***p < 0.001. ****p < 0.0001.