Project ID NS-MH2023_57

ThemeNS-MH

Co Supervisor 1A IoPPN/AddictionsWebsite

Co Supervisor 1B FoLSM/Centre for Human and Applied Physiological SciencesWebsite

Experimental TESTing on Heroin and opioid OverDose: Environmental, Respiratory and Pharmacological Mechanisms (OD-TEST)

In the UK, and globally, fatal drug overdoses are at an all-time high1,2. Opioid overdose is now the leading cause of death for people under the age of 50 in the US2. An effective antidote to opioid, Naloxone, exists but many people are alone when they overdose3,4 and any intervention requires accurate detection of overdose and the presence of another person. Furthermore, there is a significantly increased risk of overdose within the weeks following periods of cessation of opioid use because of suspected loss of tolerance5,6,7.

Remote, real-time measurement of respiratory depression (a hallmark of opioid overdose) is possible but little research exists on the mechanistic underpinnings, and comparison between remote and traditional measures. This project will uniquely study recreational heroin users who are the most vulnerable to the risk of heroin overdose and provide an important contribution to the ways in which we improve responses to overdose crises.

Aims (Fig.1 for studies):
Identify the proportion of deaths where no bystander is present (Study1);
Better understand the relationship between dose increments and respiratory depression (Study2a);
Identify accuracy of wearable technology in detection of opioid overdose (Study2a);
Identify whether hypercapnic drive responses differ between ex and current users of opioids (Study2b).

Skills:
Statistically analysing large datasets; clinical study development; respiratory physiology techniques; wearable/mobile technologies; controlled human drug administration experiments.

Objectives:
Year 1: Conduct Study1 and obtain final approvals for Study2
Year 2: Recruit users and ex-users for Study2a and 2b
Year 3: Analysis of Study2 and write up

Figure 1: NPSAD= National Programme of Substance Abuse Deaths; SpO2% = pulse oximetry; ETCO2% = end-tidal CO2; RR= Respiratory Rate; NRD EMG = Neural Respiratory Drive as measured by Electromyography of 2nd parasternal intercostal muscles. References available on request.

Representative Publications

Heroin-induced respiratory depression and the influence of dose variation: within-subject between-session changes following dose reduction. Tas, B., Jolley, C., Kalk, N., Bell, J., van der Waal, R. & Strang, J. 2020, In: Addiction. 115, 10, p. 1954-1959

Undetected Respiratory Depression in People with Opioid Use Disorder Tas, B., Kalk, N., Lozano- García, M. Rafferty, GF., Cho, P.S.P., Kelleher, M., Moxham, J., Strang, J. & Jolley, C. J. 2022, In: Drug and alcohol dependence. 234, 109401.