Tehran University of Medical Sciences Iranian Journal of Parasitology 1735-7020 14 3 2019 09 18 394 403 EN Javad JABARI Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Fatemeh GHAFFARIFAR Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran John HORTON Tropical Projects, Hitchin, UK Abdolhosein DALIMI Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Zohreh SHARIFI Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran 2018 02 04 2019 09 18 Background: In this research, the effect of morphine on promastigotes and amastigotes of Leishmania major has been investigated in the presence of nalmefene as a blocking opioid drug and imiquimod as an opioid growth factor receptor. Methods: This study was conducted at Tarbiat Modares University, Tehran, Iran in 2015-2018. Morphine with different concentration (0.1, 1, 10 and 100 1µg/ml) alone and with imiquimod (0.01, 0.1 and 1µg/ml) and nalmefene (0.1, 1 and 10 µg/ml) on promastigotes and amastigotes in macrophages and also the percentage of infected macrophages was investigated. For evaluation of the apoptosis, we used flow cytometry method. The effect of imiquimod and nalmefene on glucantime and amphotericin B as current drugs for treatment of leishmaniasis was evaluated too. Results: The effect of morphine on promastigotes and amastigotes has a reverse relationship with its concentration. The results of flow cytometry for drug-treated promastigotes revealed that apoptosis and necrosis did not increase markedly relative to the control group. A combination of morphine and imiquimod in concentrations of 0.05, 5 and 5 µg/ml had a pronounced effect on reduction and prevention of macrophage infection with amastigotes. Morphine at a concentration of 0.1 µg/ml plays the role of adjunctive treatment. In amastigote assay we found the better results in group that get glucantime 25 µg/ml+ imiquimod 0.5 µg/ml. Conclusion: This effect is strengthened with imiquimod and weakened with nalmefene. Using high dose morphine and nalmefene had reverse effects. They suppress immune system and had no controlling effect in macrophages amastigote infection and reduction of promastigotes. https://ijpa.tums.ac.ir/index.php/ijpa/article/view/1987 https://ijpa.tums.ac.ir/index.php/ijpa/article/download/1987/963