A Wayne State University researcher is using a three-year, $2.6 million grant from the National Institute on Drug Abuse of the National Institutes of Health to learn more about the links between stress and drug use by applying behavioral economics.

Mark Greenwald, Ph.D., professor of psychiatry and behavioral neurosciences in the School of Medicine and director of the Substance Abuse Research Division, will study a group of heroin users to see how pharmacologically induced stress affects their decisions to seek money or drugs when given the choice. Over the next three years, 30 participants will be selected from more than 100 heroin-addicted volunteers who currently are not being treated; then, they will undergo extensive screening.

"The application of this research is potentially much more far reaching than heroin abuse or even substance abuse," Greenwald said, adding that it also could affect treatment for other addictive disorders or obesity.

While medications exist to treat drug addiction, alcohol abuse and cigarette smoking, he said, they don't directly tackle stress, which is the focus of his study and one of the key precipitators of drug use and relapse.

"In biological terms, stress means pushing the organism beyond its normal homeostatic limits so that it's forced to adapt to a more challenging situation, and that produces both biological and behavioral effects," Greenwald said. "Those are things we're capable of measuring in a controlled, experimental human laboratory setting."

Study participants will be given different oral doses of yohimbine, which has been shown to increase drug-seeking behavior, and different oral doses of hydrocortisone, another stress inducer. During the inpatient study period, participants will be stabilized on buprenorphrine, a medication known to mitigate heroin withdrawal symptoms.

During multiple three-hour sessions, each participant will be presented with 12 opportunities to work on a computer task for money or the drug Dilaudid, an opioid painkiller whose effects are similar to that of heroin. With each choice they make, however, the response cost - the "price" of earning money or the drug - exponentially increases. Before the work sessions, they will receive placebo, yohimbine alone, hydrocortisone alone, or the combination of yohimbine and hydrocortisone, in random order. During each session participants will be given the chance to work for money, drugs or a mixture of both, or they may choose not to work at all.

Researchers then will record how varying the levels of stressors - or withholding them - affects drug-seeking behavior. Greenwald predicts that higher stress levels will result in more drug seeking. He said that actually measuring those levels is a chance to develop a deeper appreciation for the mechanisms by which stress increases drug use. For instance, the behavioral economic approach will be used to examine whether stressors increase drug seeking regardless of drug price, or only when drug price is high.

Researchers will track some biological reactions and note participants' self-reported mood changes. Learning and memory functions known to be sensitive to emotion-inducing situations also will be measured.

In an experimental setting, Greenwald said, money has been shown to be a good generalized alternative to drugs, and that combining non-drug incentives with anti-stressor medication could be used to drive down drug demand. He believes his study will have broad importance because it will enable better understanding of how stress might increase drug use of all types, and perhaps at different phases of the addiction cycle.

That understanding could lead to more individually tailored treatments that combine anti-stress medications, other medications and behavior therapies, Greenwald said, adding that combining therapies works better than using them in isolation. Treatment in many cases can be a better alternative to the incarceration that many substance abusers now face.

"There's good reason to think that more cost-effective use of resources than just across-the-board incarceration can tip the balance in favor of treatment," he said. "Our hope is that in the long run it will be a great benefit to all substance abusers and society in general, given that stress is something that can lead to the initiation of drug use. Hopefully that will help society by bringing down the costs of dealing with substance abuse so we can allocate our resources elsewhere."

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Wayne State University is one of the nation's pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit http://www.research.wayne.edu.