The cannabinoid CB2 receptor agonist LY2828360 synergizes with morphine to suppress neuropathic nociception and attenuates morphine reward and physical dependence.

The cannabinoid CB2 receptor agonist LY2828360 synergizes with morphine to suppress neuropathic nociception and attenuates morphine reward and physical dependence. Eur J Pharmacol. 2020 Sep 04;:173544 Authors: Iyer V, Slivicki RA, Thomaz AC, Crystal JD, Mackie K, Hohmann AG Abstract The opioid crisis has underscored the urgent need to identify safe and effective therapeutic strategies to overcome opioid-induced liabilities. We recently reported that LY2828360, a slowly signaling G protein-biased cannabinoid CB2 receptor agonist, suppresses neuropathic nociception and attenuates the development of tolerance to the opioid analgesic morphine in paclitaxel-treated mice. Whether beneficial effects of LY2828360 are dependent upon the presence of a pathological pain state are unknown and its impact on unwanted opioid-induced side-effects have never been investigated. Here, we asked whether LY2828360 would produce synergistic anti-allodynic effects with morphine in a paclitaxel model of chemotherapy-induced neuropathic pain and characterized its impact on opioid-induced reward and other unwanted side-effects associated with chronic opioid administration. Isobolographic analysis revealed that combinations of LY2828360 and morphine produced synergistic anti-allodynic effects in suppressing paclitaxel-induced mechanical allodynia. In wildtype (WT) mice, LY2828360 blocked morphine-induced reward in a conditioned place preference assay without pr...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research