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Looking for secrets to drug addiction in our blood

RICHLAND, Wash. -- A new collaboration between the Department of Energy's Pacific Northwest National Laboratory and the Air Force's 59th Medical Wing hopes to improve on drug tests for illicit drug use and abuse. Not only are the researchers looking for a better indicator of current or past use, but they'd like to be able to identify people prone to abusing drugs in the first place.

Funded by the Department of Defense, the $850,000 two-year study will lay the foundation for future work to determine who might be susceptible to hydrocodone. Initially, the collaboration will map out drug breakdown products, proteins and other compounds that healthy bodies make in response to the prescription painkiller hydrocodone.

"We want to enhance the prevention, diagnosis and treatment of drug addiction. Our military deserves the best care we can give them," said Lt. Col. (Dr.) Vikhyat Bebarta, a research physician in the 59th Medical Wing at Lackland Air Force Base near San Antonio, Texas. Bebarta will be co-leading the study with biochemist Josh Adkins of PNNL.

The results will likely extend beyond the military. "Any tools for drug addiction that come out of this study could also be used by the general public," said Adkins.

Just as some genes confer a susceptibility to alcoholism, the team hopes to find some indicator of susceptibility to dependence on painkillers such as hydrocodone. Instead of a gene, though, the researchers hope to find a difference in how a susceptible person responds to the drug, compared to a nonsusceptible one. If such an indicator exists in blood, urine or saliva, not only would it improve our understanding of the biological response to hydrocodone, but tests that reveal the indicator could be developed.

Dependency tendency

The painkiller hydrocodone is one of the most abused drugs in the U.S. Its use, abuse and addictive potential pose special concern for the armed forces, whose members suffer trauma more often than the average civilian. Hydrocodone is an opioid closely related to the opiate morphine. Both military and civilian doctors are prescribing hydrocodone more often, making it more accessible for people to misuse and abuse.

The rising prescription rate and greater availability has likely contributed to an increase in number of patients in treatment. Admission for drug abuse treatment programs for hydrocodone and related opiates more than quadrupled between 1997 and 2007, according to a 2007 report from the National Admissions to Substance Abuse Treatment Services. (This does not include the opiate heroin, which remained stable over that time.)

Knowing if a military member is misusing or abusing hydrocodone is essential to national security and to the safety of military personnel. In 2005, the Department of Defense found that 7.3% of active duty personnel across all branches of the military had used analgesics including hydrocodone without a medical need in the previous year.

Finding users

Doctors have several tests to determine who is using hydrocodone or other illicit drugs, but they are inadequate. The simplest -- a screening questionnaire -- is not definitive. And current blood or urine tests for hydrocodone only determine whether the drug been used in the last few hours or days. In addition, several drugs cross react in the blood test, making them unreliable.

More important, there is no current screening test for recent or past hydrocodone use. Psychotherapeutics rank right behind marijuana as the most commonly abused drugs among the military and civilians, and hydrocodone and other pain relievers are the most popular of the psychotherapeutics.

To determine if someone had been using hydrocodone in the recent past, the researchers will take snapshots of changes that can be detected in blood or urine. "We already know how it works in the brain, so we will focus on the body. Hydrocodone has a physiological response on the whole body to fight pain," said Bebarta.

The first part of the study seeks to determine the baseline for what hydrocodone does to normal healthy subjects. The researchers will look for changes to a variety of body systems after healthy volunteers take the drug. The systems they're looking at include the pain response, inflammation, and stress -- all known to be involved in hydrocodone's effect.

"Partnering with the 59th Medical Wing takes advantage of the strengths in each group," said PNNL biologist Karin Rodland, chief scientist for biomedical research and co-investigator on the team.

Because the Air Force researchers have extensive expertise in toxicology and drug metabolism at Wilford Hall Medical Center in San Antonio, they will perform the part of the study that looks at how hydrocodone gets metabolized. Backed by PNNL's expertise in the field of proteomics, the PNNL team will check for changes in about 2000 different protein levels using state-of-the-art instruments in EMSL, DOE's Environmental Molecular Sciences Laboratory on the PNNL campus.

The baseline studies will take two to three years to complete. Armed with a baseline, the researchers will be able to conduct other experiments with hydrocodone-dependent patients to look for indicators that identify those who are most likely to abuse it.

Eventually, the team's goal is for a clear understanding of a dependent patient's complete physiological response to opioids. They are hopeful they will find a susceptibility marker and discover new ways to personalize opioid pain medicine. "That would require a systems biology level of understanding of a person's response to opiate," said Rodland, "but we hope we get the chance to try."


Contact: Mary Beckman
DOE/Pacific Northwest National Laboratory

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