Research into opioid painkillers could provide clues for safer drug development

Researchers have taken a step closer to understanding the body’s response to opioid painkillers such as morphine and fentanyl, which could lead to the development of safer opioid drugs.

Opioids are a class of powerful painkillers used to treat moderate to severe pain. They act on the nervous system, stimulating opioid receptors which then block pain. But continued use can lead to physical dependence and withdrawal symptoms, partly because the body’s tolerance builds up quickly and pain control diminishes.Now, research published in ‘Nature Communications’ has identified the specific molecular mechanisms in the body which respond to the opioids and cause this increasing tolerance. Dr Alexis Bailey at St George’s, University of London was part of the research team, which was led by Professor Schulz of Jena University Hospital, Germany. The researchers developed genetically modified mice that lacked phosphorylation sites of the ‘mu’ (µ) opioid receptor, the target of opioid painkillers in the central nervous system. These mice subsequently built up very little tolerance to opioids such as fentanyl and morphine. As a result, the painkilling effect of these drugs was dramatically increased. But the side effects of the drugs, such as constipation, respiratory depression and withdrawal symptoms, remained unchanged or were exacerbated. The researchers’ findings show that tolerance and dependence are two dissociable phenomena governed by separate molecular mechanisms. While it had been demonstrated that these “mu” phosphorylation sites played a role in opioid tolerance in cells, this is the first time it has been proven in animal models. In 2017, 23.8 million prescriptions were dispensed for opioids such as tramadol in England – one for every two adults. Hospital admissions in the UK involving opioid overdoses have almost doubled in a decade to 2017. Dr Alexis Bailey, Lecturer in Neuropharmacology at St George’s, said: “So-called ‘safe opioids’ that are less likely to result in dependence, tolerance and risk of accidental overdose have been the Holy Grail of opioid research. This study takes us a step closer to understanding the underlying molecular mechanisms of how they work on the body, which is an absolute prerequisite to devising new strategies for drug development.”

opiod pills

E-cigarettes research shows clear benefits of switching from tobacco

October has been designated ‘Stoptober’ again by the NHS as part of its ongoing campaign to persuade us to stop smoking.

Latest figures from the WHO show that smoking is still the number one preventable disease, killing seven million people globally each year. Stoptober is timely for Senior Lecturer Alexis Bailey who has presented preliminary results from his research on e-cigarettes at SRNT, the top nicotine and tobacco research conference, in Munich last month.There has been a meteoric rise of electric cigarette use in the UK since their introduction in 2006. In the UK, e-cigarettes are used by smokers to help them stop smoking as well as by former smokers, and it is estimated that there are 3.2 million e-cigarette users in the UK alone.


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