{
    "abstract": "Oral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine-naloxone dose ratio for an abuse-deterrent oral opioid formulation.\nIn a randomized, double-blinded, 2 \u00d7 2 cross-over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 100:1 (75 mg: 0.75 mg; [morphine-naloxone 100:1]) or 200:1 (75 mg: 0.375 mg; [morphine-naloxone 200:1]). Acute naloxone-induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale-German [SOWS-G]) and observer-rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated.\nIntravenous morphine-naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose-dependently (morphine-naloxone 100:1 > morphine-naloxone 200:1) increased SOWS-G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone.\nMorphine-naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine-naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.",
    "authors": [
        {
            "affiliation": "Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.",
            "firstname": "Stefan",
            "initials": "S",
            "lastname": "Weisshaar"
        },
        {
            "affiliation": "Department of Applied Psychology: Work, Education & Economy, Faculty of Psychology, University of Vienna, Vienna, Austria.\nCenter for Public Health, Medical University of Vienna, Vienna, Austria.",
            "firstname": "Laura",
            "initials": "L",
            "lastname": "Brandt"
        },
        {
            "affiliation": "Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.",
            "firstname": "Brigitte",
            "initials": "B",
            "lastname": "Litschauer"
        },
        {
            "affiliation": "Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.",
            "firstname": "Safoura",
            "initials": "S",
            "lastname": "Sheik-Rezaei"
        },
        {
            "affiliation": "Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.",
            "firstname": "Laura",
            "initials": "L",
            "lastname": "Moser"
        },
        {
            "affiliation": "Bioconsult GmbH, Breitenfurt, Austria.",
            "firstname": "G\u00fcnther",
            "initials": "G",
            "lastname": "Nirnberger"
        },
        {
            "affiliation": "G. L. Pharma GmbH, Lannach, Austria.",
            "firstname": "Elisabeth",
            "initials": "E",
            "lastname": "K\u00fchberger"
        },
        {
            "affiliation": "G. L. Pharma GmbH, Lannach, Austria.",
            "firstname": "Ulrike",
            "initials": "U",
            "lastname": "Bauer"
        },
        {
            "affiliation": "Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.",
            "firstname": "Christa",
            "initials": "C",
            "lastname": "Firbas"
        },
        {
            "affiliation": "Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.",
            "firstname": "Ghazaleh",
            "initials": "G",
            "lastname": "Gouya"
        },
        {
            "affiliation": "Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.",
            "firstname": "Michael",
            "initials": "M",
            "lastname": "Wolzt"
        },
        {
            "affiliation": "Center for Public Health, Medical University of Vienna, Vienna, Austria.",
            "firstname": "Gabriele",
            "initials": "G",
            "lastname": "Fischer"
        }
    ],
    "conclusions": "Morphine-naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine-naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.",
    "copyrights": "\u00a9 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.",
    "doi": "10.1111/bcp.14271\n10.1136/bcr-2015-210239",
    "journal": "British journal of clinical pharmacology",
    "keywords": [
        "morphine",
        "naloxone",
        "opioid maintenance treatment",
        "opioid withdrawal syndrome",
        "substance abuse-intravenous"
    ],
    "methods": null,
    "publication_date": "2020-03-08",
    "pubmed_id": "32145041\n22225671\n23762965\n15537850\n24716256\n16754753\n24766667\n9262035\n16042640\n15652441\n15563359\n24304412\n22628390\n18666382\n14563546\n20605006\n19888784\n22541841\n17012944\n21919979\n26392442\n660555\n10601678\n10961373\n8306082\n1195133\n3479162\n3687892\n21434580\n4422361\n11100892\n9293513\n15491480\n1960767\n21902287\n1267205\n22417016\n19184618\n21749526\n20403021",
    "results": "Intravenous morphine-naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose-dependently (morphine-naloxone 100:1 > morphine-naloxone 200:1) increased SOWS-G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone.",
    "title": "Dose-dependent naloxone-induced morphine withdrawal symptoms in opioid-dependent males-a double-blinded, randomized study.",
    "xml": "<Element 'PubmedArticle' at 0x788503b04c20>"
}