24 June 2022

People who inject heroin develop tolerance to the effects of the drug with repeated use over time. This means that they need larger amounts of the drug to feel the same effect. Researchers from the University of Bristol, in collaboration with Bristol Drugs Project and the UK Health Security Agency, asked people who use heroin about their experiences to gain a better understanding of how, when and why tolerance develops, what it means to them, and the implications for future research and harm reduction services.

Group discussion

Heroin injection produces a range of effects, including euphoria, sedation, respiratory depression (slow and ineffective breathing), analgesia, constipation and miosis (constriction of eye pupils).

Most people who used heroin interviewed in the study (n=20) said that tolerance developed more rapidly following their most recent relapse after a period of abstinence compared to their first relapse. Most participants were not aware of tolerance to respiratory depression (effects on breathing) developing. Tolerance was experienced as interacting and co-developing with physical dependence and the symptoms of withdrawal. Several participants did not differentiate between tolerance and dependence. This has implications for harm reduction services in that discussions around tolerance should also consider dependence.

Participants also reported experiencing fluctuations in tolerance levels, increasing over periods of regular use and reducing when abstinent. Using more drug was the most common response to increasing tolerance to the desired effects. Tolerance was also perceived to return more quickly with each abstinence-relapse cycle:

“The more times I have a time of abstinence and then go back to it, the quicker the tolerance level shoots right up like a thermostat on a hot day.” (Participant from the study)

Dr Jo Kesten, Research Fellow at the NIHR Health Protection Research Unit in Behavioural Science and Evaluation at University of Bristol and lead author of the study, said: “While the multi-faceted nature of tolerance has been acknowledged previously in theoretical literature, this new study addresses the gap in evidence on the lived experience of tolerance, particularly the rate of tolerance returning following repeated episodes of abstinence. It’s been great to work on this translational study at the intersection between pharmacology and lived experience.

Professor Graeme Henderson, from the School of Physiology, Pharmacology and Neuroscience at the University of Bristol, said: “By explaining the mechanisms identified in this study and potentially discovering how they could be switched on prior to relapse we might be able to develop a beneficial harm reduction treatment for people in abstinence that would protect against overdose occurring on subsequent relapse. There is a need for future research to define the neurochemical changes in the brain responsible for these findings.”

Rachel Ayres, Volunteer Manager at Bristol Drugs Project (BDP), said: “These findings have important implications for harm reduction services like BDP. We plan to look at how we can raise awareness among people who use our services of the different aspects of tolerance and the risk of overdose despite tolerance to the desired effects of the drug.”

Paper: Changes in the development of opioid tolerance on re-exposure among people who use heroin: a qualitative study by Joanna May Kesten, Ed Holder, Rachel Ayres, Pete Ellis, Steve Taylor, Matthew Hickman and Graeme Henderson. Published in PLOS One. June 2022.

Further information 

About the NIHR Health Protection Research Unit [HPRU] in Behavioural Science and Evaluation at the University of Bristol

The NIHR HPRU in Behavioural Science and Evaluation at University of Bristol is one of 14 HPRUs across England, part of a £58.7 million investment by the NIHR to protect the health of the nation.

The NIHR HPRU in Behavioural Science and Evaluation is a partnership between the UK Health Security Agency (UKHSA) and University of Bristol, in collaboration with MRC Biostatistics Research Unit at the University of Cambridge and University of the West of England.

Each NIHR HPRU undertakes high quality research that is used by UKHSA to keep the public safe from current and emerging public health threats.

About the NIHR

The National Institute for Health and Care Research (NIHR) is the nation’s largest funder of health and care research. The NIHR:

  • funds, supports and delivers high quality research that benefits the NHS, public health and social care
  • engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
  • attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
  • invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
  • partners with other public funders, charities and industry to maximise the value of research to patients and the economy.

The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR supports applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK aid from the UK government.