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Independent groups of male Swiss Webster mice were i.p. injected with 100\u2009mg\/kg morphine, 31.6\u00a0mg\/kg levamisole (lethal doses at 10%, LD<jats:sub>10<\/jats:sub>) or the same doses combined. Naloxone pretreatment (10\u00a0mg\/kg, i.p.) prevented morphine\u2010induced death, as did 2.5\u00a0mg\/kg, i.p. mecamylamine with levamisole. Co\u2010administration of levamisole and morphine (Lvm\u2009+\u2009Mor) increased lethality from 10% to 80%. This augmented effect was prevented by 30\u2009mg\/kg, i.p. naloxone and reduced with 10\u00a0mg\/kg naloxone plus 2.5\u00a0mg\/kg, i.p. mecamylamine. In independent groups of mice, 17.7\u00a0mg\/kg, i.p. levamisole antagonized the acute morphine's antinociceptive effect evaluated in the tail\u2010flick test. Repeated 17.7\u00a0mg\/kg levamisole administration (2\u00d7\/day\/3\u00a0weeks) did not affect tolerance development to morphine (10\u00a0mg\/kg, 3\u00d7\/day\/1\u00a0week). Blood samples obtained from mice repeatedly treated with levamisole showed leukopenia and neutropenia. Morphine also produced neutropenia, increased erythrocyte count and other related parameters (e.g. haemoglobin). Lvm\u2009+\u2009Mor had similar effects on leukocyte and neutrophil counts to those seen with levamisole only, but no erythrocyte\u2010related alterations were evident. Blood chemistry analysis did not indicate liver damage but suggested some degree of electrolyte balance impairment. In conclusion, Lvm\u2009+\u2009Mor increased death risk, altered morphine\u2010induced antinociceptive effects and produced haematologic abnormalities. The importance of studying combinations of drugs of abuse lies in the fact that drug users frequently combine drugs, which are commonly adulterated.<\/jats:p>","DOI":"10.1111\/adb.13166","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:14:37Z","timestamp":1648426477000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Co\u2010administration of morphine and levamisole increases death risk, produces neutropenia and modifies antinociception in mice"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-7994","authenticated-orcid":false,"given":"Ana K.","family":"Ruiz\u2010Qui\u00f1onez","sequence":"first","affiliation":[{"name":"Departamento de Farmacobiolog\u00eda Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional (Cinvestav, IPN)  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0168-7284","authenticated-orcid":false,"given":"Zyanya P.","family":"Espinosa\u2010Riquer","sequence":"additional","affiliation":[{"name":"Departamento de Farmacobiolog\u00eda Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional (Cinvestav, IPN)  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9117-1611","authenticated-orcid":false,"given":"C\u00e9sar J.","family":"Carranza\u2010Aguilar","sequence":"additional","affiliation":[{"name":"Departamento de Farmacobiolog\u00eda Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional (Cinvestav, IPN)  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Thom","family":"Browne","sequence":"additional","affiliation":[{"name":"Colombo Plan Secretariat Drug Advisory Program  Colombo Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8617-3556","authenticated-orcid":false,"given":"Silvia L.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Departamento de Farmacobiolog\u00eda Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional (Cinvestav, IPN)  Mexico City Mexico"},{"name":"Faculty of Medicine National Autonomous University of Mexico  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,27]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"CDC.Understanding the epidemic. 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