{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T19:47:51Z","timestamp":1764445671173,"version":"3.46.0"},"reference-count":17,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aim<\/jats:title>\n                    <jats:p>Globally, more than 100\u2009000 people die annually from opioid overdose. Although strongly implicated in heroin overdose deaths, acute opioid\u2010induced respiratory depression is poorly understood, and few laboratory studies have been completed in human subjects. It is an area of undone science. Using a human laboratory overdose model, our research question was: what is the strength of the association between increasing dose of diamorphine and degree of respiratory depression in people prescribed injectable diamorphine for heroin use disorder?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Single\u2010blind, Phase IV, non\u2010randomised, dose\u2010escalation clinical trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>King's Clinical Research Facility, London, UK.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Four participants prescribed injectable diamorphine as treatment for heroin use disorder [all male, median (range) age 63 (59\u201372)].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>The following dosing schedule was implemented (as a % of participant's usual prescribed diamorphine dose): visit 1\u2013100%; visit 2\u2013110%; visit 3\u2013120%; visit 4\u2013100%. Usual dose: 97.5\u2009mg (30\u2009mg\u2013200\u2009mg).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>\n                      Physiological measures included: pulse oximetry (SpO\n                      <jats:sub>2<\/jats:sub>\n                      %), end\u2010tidal CO\n                      <jats:sub>2<\/jats:sub>\n                      (ETCO\n                      <jats:sub>2<\/jats:sub>\n                      %), transcutaneous CO\n                      <jats:sub>2<\/jats:sub>\n                      , respiratory rate and parasternal electromyography to measure neural respiratory drive index (NRDI). Recordings were made continuously from 3 mins pre\u2010dose to 60 mins post\u2010dose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      Respiratory measures from baseline to post\u2010dose across all dose sessions had ranges of: 89.7%\u201399.5% SpO\n                      <jats:sub>2<\/jats:sub>\n                      %; 4.8%\u20137.7% ETCO\n                      <jats:sub>2<\/jats:sub>\n                      %; 5.2\u201313.4 breaths\/minute respiratory rate; 51.2\u00a0min\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u2013165.9\u00a0min\n                      <jats:sup>\u22121<\/jats:sup>\n                      NRDI across all participants. All diamorphine doses caused some reduction in respiratory function. There was no clear difference between diamorphine dose and the degree of respiratory depression, based on descriptive analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A dose\u2010escalation clinical trial of people prescribed injectable diamorphine for heroin addiction found that the degree of respiratory depression caused by diamorphine does not appear to be dose dependent; however, the changes seen at diamorphine doses to which participants were accustomed suggest that participants had only partial tolerance to the respiratory depressant effect of diamorphine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/add.70005","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:31:21Z","timestamp":1739233881000},"page":"1253-1259","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A heroin overdose laboratory model: How do escalating doses of diamorphine alter respiratory function in a diamorphine\u2010treated population?"],"prefix":"10.1111","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3137-7631","authenticated-orcid":false,"given":"Basak","family":"Tas","sequence":"first","affiliation":[{"name":"National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Addictions Department King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3820-9243","authenticated-orcid":false,"given":"Nicola 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Psychology and Neuroscience (IoPPN), Addictions Department King's College London  London UK"},{"name":"Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline J.","family":"Jolley","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine King's College Hospital NHS Foundation Trust, King's Health Partners  London UK"},{"name":"Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5413-2725","authenticated-orcid":false,"given":"John","family":"Strang","sequence":"additional","affiliation":[{"name":"National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Addictions Department King's College London  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