Many people fear that mere exposure to prescription painkillers like Vicodin or OxyContin will set them down the road to addiction. But new research on the response to opioid medication suggests that most people don’t particularly like the experience of using the drugs — a key factor in future addiction risk.
Researchers led by Dr. Martin Angst of Stanford University studied 114 pairs of identical twins aged 18 to 70, none of whom had chronic pain or addiction. Participants received intravenous infusions of either placebo or the opioid alfentanil, a drug that is approximately 10 times stronger than heroin and is used as an anesthetic during surgery. IVs are known to be the most addictive route of drug administration.
According to the findings, published in the journal Anesthesiology, 14% of participants said they disliked the opioid experience outright. About 6% found it neither pleasant nor unpleasant and 52% had mixed feelings about it; 23% of those with mixed feelings said they disliked it more than they liked it. Less than one-third (29%) of volunteers said they liked the opioid experience unreservedly. “If you would split it up, you would say about a quarter really didn’t like it and a quarter really liked it a lot,” says Angst, a professor of anesthesia at Stanford.
Researchers study drug liking as a sign of addiction risk; not surprisingly, people do not usually become addicted to drugs they don’t like. But liking alone doesn’t necessarily lead to addiction; otherwise addiction rates would be at least double what they appear to be now: research on recreational use of heroin finds, for example, that 69% of those who try the drug are not using it at all a year later, while 13% are addicted. For prescription opioids, 57% who try the drugs non-medically aren’t using them a year later; 3% are addicted.
In line with earlier research, which shows that most healthy people given opioids do not find the experience overwhelmingly pleasurable, the current study also found that older people were more likely they were to dislike opioids. That may help to explain why older people are at far less risk of developing new addictions, compared with people in their 20s or younger. The most recent data from the National Household Survey on Drug Use and Health, for instance, finds that while 8% of people aged 18 to 25 have some type of illegal drug problem, just 2% of those over 26 do.
Curiously, however, the Stanford researchers did not find a genetic link to drug liking: identical twins were no more likely to share a taste (or distaste) for the painkiller than a comparison group of fraternal twins. If genes played a strong role, one would expect to see more comportment among the identical twins, who have the exact same DNA. It’s possible, however, that the link simply didn’t show up in the current study because the sample wasn’t large enough; the study did find that family members (i.e., either type of twin) were more similar in their drug liking than nonrelatives .
“It’s very well possible that liking may have a genetic component, [even accounting for] up to 30%,” of the variance in risk, says Angst. “That’s still possible, we just can’t say from a statistical point of view.”
The study found also that people’s perceptions of pain relief from alfentanil varied significantly — another crucial factor in the debate over the risks of opioid use for pain. In the study, when exposed to pain caused by heat, “maybe 20% to 25% didn’t have a significant analgesic response at all,” Angst says. This response seemed to be associated with genetics, however, depending on the type of pain presented: 12% of the pain relief from heat pain experienced in response to the drug was linked to genetics, while 60% of the relief from pain due to cold was attributable to genetic background.
“Our study, if anything, shows the diverse range of responses in essentially all outcomes,” says study co-author David Clark.
The findings may help partly explain why people’s responses to opioids are so divergent. Some people experience incredible pain relief from the drugs, while others get nothing but severe side effects, such as nausea and dangerous slowing of breathing. Some become euphoric; others depressed. Some become rapidly addicted, while others can take the drugs for years and then easily stop when their pain goes away. These facts offer simultaneous evidence for increased access to powerful painkillers and calls for total bans on them.
Meanwhile, another new study published in the journal Addiction reviewed the literature on addiction risk following exposure to opioid medication for pain. The data on the subject are not very strong, the review suggests, but they do show a wide range of risk: anywhere from 0% to 24% of people treated for chronic pain or cancer pain can expect to develop a new addiction. However, the average risk found in the data is less than half a percent, meaning that the studies showing extremely high percentages represent outliers.
“We have an immense problem because we don’t understand who is at risk and under what circumstances,” says Clark in reference to the rates of prescription painkiller overdose and addiction, which have been skyrocketing in recent year.
The takeaway is that there is no such thing as an “average” pain patient, notes Angst. Doctors need to understand each patient’s specific needs and risk factors in order to tailor their treatment better. Certainly, restricting access to pain relief isn’t the best answer. “We can’t throw the baby out with the bathwater. It’s not black and white. There are grays and dealing with shades of gray is just more complicated,” he says.