Opiate Reactions May Be Linked to Genetics

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How the body responds to opiates — the powerful, pain-relieving drugs that carry a high potential for addiction — may be partly determined by genetics, according to a new study.

Researchers studied 121 pairs of twins to look at the role of genetics in people's reactions to the pain medications. They found that genetic predisposition accounted for 59 percent of the variation between people's levels of nausea, 36 percent of the differences in how much people disliked the drug and 38 percent of the variation in itchiness in reaction to the drug.

The findings are important because the degree to which people experience unpleasant side effects, and like or dislike the drugs, can be a sign of how effectively the drugs treat their pain, and their potential to develop addiction, the researchers said. Liking a drug increases the susceptibility to addiction, while experiencing negative side effects decreases it.

“Genetics matter…people are different, and if we understand why they are different, we can take better care of them,” said study author Dr. Martin Angst, professor of anesthesia at the Stanford University Medical Center.

It's well-known that the pain relievers cause extremely different reactions in people, but the new study gives researchers a better understanding of how genetics could play a role in those reactions.

"Patients vary dramatically in how much pain relief they get, what extent they suffer from opiates and how much pleasure they get from opiates,” Angst said.

Opiates: reactions and addictions

Nearly 2 million people in the U.S. are addicted to prescription painkillers, a 2009 government survey found, and the problem is growing. Painkiller addiction often begins with a patient taking legitimate prescriptions.

Researchers believe the addiction problem could be curbed if people's reactions to the drugs were better understood, or could be predicted. Some patients may require 10 times the typical dose for adequate pain relief; others prefer lower doses that cause less extreme side effects, even though it means experiencing more pain.

In the study, participants were randomly assigned to receive either a small amount of a short-acting opiate or a placebo, followed by a heat probe or ice-cold water. Researchers spent 6 hours with each participant, but didn't know which treatment they'd received. General tolerance to pain was also assessed by applying the heat probe or cold water without any medication.

The study demonstrated that one of the most uncomfortable side effects, nausea, is strongly inherited, as genes account for almost two-thirds of variability between people.

The more severe side effects that come with opiates include slow breathing, which can result in death. Genetics accounted for 30 percent of the variation between people in respiratory depression, and 32 percent of dizziness, the study found.

Opiates represent a "double-edged sword — they’re really important drugs to relieve pain, but they come along with side effects," Angst said.

More personalized treatment

This line of research could result in a more personalized approach to administering the medications, the researchers said. Someday, people could be screened prior to use so doctors could understand their predispositions, and respond appropriately.

For example, screening could prevent a patient with a low tolerance for opiates from getting a high dose that could bring such euphoric feelings that they predispose the person to seek out the drug in the future, which could be the start of an addiction, said Dr. Doo-Sup Choi, who studies addiction at the Mayo Clinic.

Angst said further research must be done to determine which genes affect tolerance.

The study of 242 participants was large considering the amount of time spent with participants, and it was well-designed and well-performed, Choi said.

The study was published today (June 20) in the journal Anesthesiology.

Pass it on: Whether patients experience side effects from opiates, or how much they will like being on the drug, may be partly due to genetics.

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