Substantial evidence has shown that activation of kappa opioid receptors (KOR) by agonists and endogenous opioid peptides in vivo may produce a strong analgesic effect that is free from the abuse potential and the adverse side effects of mu-opioid receptor (MOR) agonists, such as morphine. In addition, activation of the KOR has also been shown to exert an inverse effect on morphine-induced adverse actions, such as tolerance, reward, and impairment of learning and memory.1


Kappa opioid receptor agonists that act within the CNS are reported to produce dysphoria and hallucinations. These symptoms have not been reported with single or multiple intravenous doses of the peripherally restricted kappa opioid receptor agonists2.


In a single-center, randomized, double-blind, active- and placebo-controlled, 4-way crossover study, overall Drug Liking and Take Drug Again VAS scores were significantly lower in either dose of a peripherally acting KORA (P<0.0001) vs. a Schedule IV drug pentazocine (0.5 mg/kg). Overall Drug Liking and Take Drug Again VAS scores following either dose of the peripherally acting KORA were similar to those observed with placebo.

1 Wang YH, Sun JF, Tao YM, Chi ZQ, Liu JG. The role of kappa-opioid receptor activation in mediating antinociception and addiction. Acta Pharmacol Sin 2010 September;31(9):1065-70
2 Webster LR et al. CR845, a Novel Peripherally Acting Kappa Opioid Receptor Agonist, Has Low Abuse Potential Compared With Pentazocine. Presented at the American Pain Society 34th Annual Scientific Meeting, May 13-16, 2015, Palm Springs, CA.