Synthetic Cannabidiol (CBD) Evaluated Within the Preclinical Screening Platform for Pain

Partial activation of the cannabinoid 1 receptor (CNR1) with a potency of 50nM was noted while higher concentrations inhibited CNR1 in functional in vitro screens. Following PO administration (10 mg/kg) maximal CBD levels in plasma were observed at 1.0 hour and dropped off over 2 hours in both male and female rats. Higher Cmax was noted in female than male rats at 4.28 and 1.64 µM respectively and the AUCs over the 24 hour period were greater in female versus male rats. In the accelerated rotarod assay (10, 30, 100, 300 mg/kg, PO) and the modified Irwin assay (3, 10, 30, 100 mg/kg PO), CBD did not cause any significant deficits in either male or female rats. CBD (1, 3, 10, 30 mg/kg PO) did not significantly reduce guarding behavior or mechanical allodynia behavior in the plantar incision model and did not affect either mechanical allodynia behavior or cold allodynia in the L5/L6 SNL model. 7 days of administration in the SNL model also did not have any effects on either endpoint. In the MIA model of osteoarthritis pain, however, CBD (3, 10, 30, 100 PO mg/kg) showed a statistically significant and dose dependent reversal of mechanical allodynia behavior in both sexes after repeated administration.