CBD ameliorates mechanical and cold hyperalgesia in male and female sickle mice. Effect of 20 and 50 mg/kg per day pure CBD (from Cayman) or vehicle (5% DMSO, 5% Tween 20, in sterile phosphate-buffered saline) given intraperitoneally was examined for mechanical and cold hyperalgesia and catalepsy in HbSS-BERK sickle mice before (BL) and after CBD treatment. (A) Acute effect of a single dose of CBD over a 24-hour period in female mice with (i-ii) 20 and (iii-iv) 50 mg/kg CBD and in male mice with (v-vi) 50 mg/kg CBD. (B) Chronic effect of CBD treatment daily over a period of 9 days in female mice with (vii-viii) 20 and (ix-x) 50 mg/kg CBD per day and in male mice with (xi-xii) 50 mg/kg CBD per day. (C) Nonevoked cold avoidance test after 9 days of 50 mg/kg per day CBD or vehicle treatment in male sickle mice. (D,E) Motor performance on rotarod before (BL) and after 9 days of 50 mg/kg per day CBD or vehicle treatment in female (D) and male (E) sickle mice. Mechanical and cold hyperalgesia data in panels A and B are presented as percent of BL, which also reflects the response to CBD in individual subjects. All data are expressed as mean ± SEM. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001 compared with BL. ⁺P < .05, ⁺⁺P < .01, ⁺⁺⁺P < .001, difference between vehicle and treatment at matched time points. Data (A-B) analyzed by 2-way repeated measures analysis of variance with Bonferroni’s multiple comparisons post hoc test or (C-E) Student 2-tailed t test. n = 4 to 7 per condition; age, ∼3.5 months. Abbreviations: PWF, paw withdrawal frequency; VF, von Frey.