Evaluation of the analgesic efficacy of AZD1940, a novel cannabinoid agonist, on post-operative pain after lower third molar surgical removal

Abstract Aim To evaluate the analgesic efficacy of AZD1940, a novel peripherally acting cannabinoid CB 1 /CB 2 receptor agonist, in patients undergoing third molar surgical removal. Methods This was a randomized, double-blind, placebo-controlled study in patients scheduled for surgical removal of an impacted lower third molar. Patients received a single oral dose of 800 μg AZD1940, 500 mg naproxen or placebo 1.5 h before surgery. The dose of 800 μg AZD1940 was selected based on earlier data from a single dose study in man, in which it was identified as the highest well tolerated dose. Ongoing post-operative pain (primary variable) and pain on jaw movement were assessed on a visual analog scale (VAS, 0–100 mm) from 0 to 8 h postoperatively, deriving the area under the curve of ongoing pain (VAS AUC 0–8 h ), and of pain on jaw movement (VAS JM AUC 0–8 h ). The time to requesting rescue medication (acetaminophen) was recorded. Subjective cannabinoid effects were assessed by the visual analog mood scale (VAMS). Results In total, 151 patients were randomized to AZD1940 ( n  = 61), placebo ( n  = 59) or naproxen ( n  = 31). There was no statistically significant difference in pain VAS AUC 0–8 h or in VAS JM AUC 0–8 h between AZD1940 and placebo. Naproxen significantly reduced both pain VAS AUC 0–8 h and VAS JM AUC 0–8 h as compared with placebo ( p Conclusion The CB 1 /CB 2 receptor agonist AZD1940 did not reduce post-operative pain after lower third molar surgical removal at doses exerting subjective cannabinoid effects. Implications Activation of peripheral CB 1 /CB 2 receptors per se is probably of less clinical relevance for the treatment of acute nociceptive pain in man.