- We did not expect to see any sex differences, but when we increased the stress level, the men worked harder than the women to get a stronger dose, says Siri Leknes.
Men most vulnerable
- We saw that the men made a real effort to get more. When we asked them, they replied that the opioid had not helped with their stress, nor did they feel any better, she continues.
This surprised the researchers. If the opioid did not relieve stress, why did the participants want more?
- When the pressure increased, the participants felt an urge to take more, especially the men, but it was not because it helped against negative emotions. They said they felt high, sluggish and strange, but not in a better mood.
- So it is not the effect on mood that made them want more and more, Leknes adds.
Controlled experiment
Marie Eikemo and Siri Leknes led the study, which has been published in Nature Mental Health. In it, healthy volunteers were given strong painkillers several times in the research group's laboratory, in order to investigate how stress affects the consumption of powerful painkillers, in this case oxycodone.
- In previous studies, we have been surprised by how little opioids affect the mood of healthy participants, says Eikemo.
- Perhaps opioids primarily have addiction potential when people are stressed or experiencing severe discomfort, she suggests.
In the study, the participants were given oxycodone immediately after completing demanding tasks deliberately designed to be impossible to solve, such as a job interview and karaoke in front of a critical panel, as well as very difficult maths exercises with a short time limit.
The participants came in four times. Each session lasted three hours. To obtain a larger dose, they had to complete a demanding task, such as pressing keys under time pressure.
Affects behaviour and choices
The study speaks directly to an ongoing debate in Norway and other countries on how to use strong painkillers safely, without increasing the risk of dependence and misuse.
Today, opioids are assessed primarily according to how well they relieve pain. Leknes believes that the healthcare system must pay more attention to how such medicines can also affect behaviour, decision-making - and the risk of substance misuse.
- Opioids are used to treat pain, which is a feeling. But these medicines act on the body's own opioids - the endorphin system - and therefore just as strongly influence how we behave and which choices we make.
- I think the healthcare system underestimates how opioids change people's behaviour and decisions. Perhaps that is the key to understanding why painkillers carry such a high risk of substance misuse, she says, comparing it to cravings for sweets.
Craving without pleasure
- I am, for example, very fond of crisps. When there is a bowl on the table, I simply cannot resist.
- After a while, the crisps do not even taste as good as they did at first, but I keep helping myself anyway.
- The 'craving' you experience then may be the same as we observed in the men in our study, explains Leknes.
Loved the "high"
Leknes and Eikemo have been researching opioids for around 20 years, financed by, among others, the Research Council of Norway and the large EU project OPIOIDREWARD.
The researchers often give talks on the topic and say that people frequently approach them afterwards.
- Some say that they have been given opioids for pain relief and loved it, but they do not dare take them again.
- What we know is that people who develop substance misuse problems and look back often say: 'The first time I got it, I thought it was absolutely fantastic.' Some say 'I had been holding my breath my whole life, and finally I could breathe.' Others say it was like getting a hug, Leknes explains, and adds:
- Perhaps there is a particular vulnerability in some people who have such an exceptionally positive experience?
According to Eikemo, the study's findings suggest that it can be problematic to have a strong positive experience with opioids in the middle of a highly stressful period in life.
- But what we see on average - across people - is not that opioids are experienced as so wonderful. Very many people become extremely nauseous. We had several people in the lab who threw up, she concludes.
