BACKGROUND & AIM: Globally, more than 100 000 people die annually from opioid overdose. Although strongly implicated in heroin overdose deaths, acute opioid-induced 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? DESIGN: Single-blind, Phase IV, non-randomised, dose-escalation clinical trial. SETTING: King's Clinical Research Facility, London, UK. PARTICIPANTS: Four participants prescribed injectable diamorphine as treatment for heroin use disorder [all male, median (range) age 63 (59-72)]. INTERVENTIONS: The following dosing schedule was implemented (as a % of participant's usual prescribed diamorphine dose): visit 1-100%
visit 2-110%
visit 3-120%
visit 4-100%. Usual dose: 97.5 mg (30 mg-200 mg). MEASUREMENTS: Physiological measures included: pulse oximetry (SpO FINDINGS: Respiratory measures from baseline to post-dose across all dose sessions had ranges of: 89.7%-99.5% SpO CONCLUSIONS: A dose-escalation 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.