Heroin-induced respiratory depression and the influence of dose variation: within-subject between-session changes following dose reduction

Addiction. 2020 Oct;115(10):1954-1959. doi: 10.1111/add.15014. Epub 2020 Mar 11.


Background and aims: Globally, more than 100 000 people die annually from opioid overdose. Opportunities to study physiological events in at-risk individuals are limited. This study examined variation of opioid dose and impact on respiratory depression in a chronic injecting heroin user at separate time-points during his long-term diamorphine maintenance treatment.

Design: A single-subject study over 5 years during which participant underwent experimental studies on diamorphine-induced respiratory depression, at changing maintenance doses.

Setting: A clinical research facility. Participant Male subject on long-term injectable diamorphine (pharmaceutical heroin) maintenance treatment for heroin addiction.

Measurements: Physiological measures of oxygen saturation (SpO2 ), end-tidal carbon dioxide (ETCO2 ) and respiratory rate (RR) were used to indicate severity of respiratory depression.

Findings: (1) After diamorphine injection, respiratory regulation became abnormal, with prolonged apnoea exceeding 20 sec (maximum 56 sec), elevated ETCO2 (maximum 6.9%) and hypoxaemia (minimum SpO2 80%). (2) Abnormalities were greater with highest diamorphine dose: average SpO2 was 89.3% after 100 mg diamorphine versus 93.6% and 92.8% for the two 30-mg doses. (3) However, long apnoeic pauses and high levels of ETCO2 % were also present after lower doses.

Conclusions: With marked inter-session variability, these findings corroborate observations of inconsistent relationships between opioid dose and overdose risk.

Keywords: Depression; HAT; heroin; opioid; overdose; respiratory.

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Tapering
  • Heroin / pharmacology*
  • Heroin Dependence / drug therapy*
  • Heroin Dependence / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Respiratory Insufficiency / chemically induced*


  • Analgesics, Opioid
  • Heroin