The opioid antagonist naloxone was given locally within the paw or systemically to evaluate the contribution of opioid receptors to CB2mediated antinociception created by AM1241, AM1241, and AM1241. Comparisons were made out of the opioid analgesic morphine. AM1241, AM1241, and AM1241 created antinociception to thermal, although not mechanical, stimulation of the hindpaw in naive rats. Antinociception created by AM1241 and AM1241 displayed an inverted Ushaped dose response curve. AM1241 made greater antinociception than both AM1241 Bosutinib SRC inhibitor or AM1241 in the lowest and highest amounts. Similar quantities of antinociception were observed at intermediate doses. AM1241, AM1241, and AM1241 each made CB2mediated antinociception which was blocked by SR144528 however not by rimonabant. Systemic and local naloxone blocked morphineinduced antinociception but didn’t prevent antinociceptive effects of AM1241, AM1241, or AM1241. The antinociceptive effects of the its enantiomers and CB2 selective cannabinoid AM1241, AM1241 and AM1241, are not influenced by opioid receptors. IMPORTANT WORDS: antinociception, cannabinoid Cannabis sativa Metastasis has been useful for both therapeutic and recreational uses throughout recorded history. The discovery by Mechoulam and Gaoni of 9tetrahydrocannabinol, the main psychoactive ingredient in marijuana, brought in a brand new era of research focused on understanding the functional roles of cannabinoid receptors in the nervous system. The cloning of cannabinoid CB1 and CB2 receptors and isolation of these endogenous ligands marked a change in the cannabinoid industry. Cannabinoids can no longer be looked at simply as illicit drugs of abuse, but rather represented pharmacological tools for studying the practical roles of CB1 and CB2 receptors in the nervous system. Initial of cannabinoid CB1 and CB2 receptors curbs pathological pain in animal models. CB1 receptors are localized primarily within the central nervous system and are linked to the satisfying facets of several addictive substances including alcohol, smoking, and cocaine. JZL184 Activation of CB1 receptors provides motor ataxia, hypothermia, catalepsy, and hypoactivity. The discovery of the CB2 receptor opened the door to exploring the role with this receptor as a therapeutic goal for pain and irritation. CB2 receptors are localized preferentially, although not entirely, to immune cells in the periphery and are up-regulated in the CNS in pathological pain states. CB2 agonists absence centrally mediated side effects, suggesting that they represent a promising therapeutic target for providing antinociception in the absence of unwanted side effects including psychoactivity or habit. Thus, the CB2 receptor offers the potential to split up analgesic properties of drug-abuse liability and cannabinoids.