Psychologist Receives Major Grant to Research New Drug Therapy for Alcoholism
By Gail Siegel, College of Liberal Arts
The U.S. government estimates that nearly 20 million Americans suffer from alcoholism. About one in four receives treatment for this disabling addictive disorder, but nearly half of those treated will experience a relapse within three months.
Why it is so hard to stop using alcohol and what can be done to help those struggling to quit are questions at the heart of Washington State University researcher Brendan Walker's work.
Walker, an assistant professor and neuroscientist in the Department of Psychology, has been awarded a five-year, $1.65 million grant from the National Institute on Alcohol Abuse and Alcoholism to study how chronic exposure to alcohol affects the structure and chemistry of the brain, producing neuroadaptations that contribute to depression and anxiety during withdrawal from alcohol.
Walker's goal is to develop new drug therapies that will support patient treatment compliance and long-term recovery.
Moving from bad to worse
Alcohol-induced depression and anxiety can persist long after a person has ceased drinking, and in a vicious cycle many alcoholics seek relief from these symptoms by resuming the habit.
"If you're trying to stop using drugs or alcohol, you are going to be in withdrawal and potentially you will have depression and decreased mood," said Walker. "That negative state motivates you to resume excessive alcohol use."
In general, an elevation in mood produced by alcohol use is followed by a compensating decline. After prolonged exposure to alcohol, a person's baseline emotional state drops.
"Our set point for mood is shifted down," said Walker. "If you stop using drugs, you're down, and even if you are using drugs you're not getting to where you were."
A likely culprit
Walker believes the neurotransmitter dynorphin may contribute to the mood-altering effect. It works in the brain similarly to the more familiar endorphin, which produces a feeling of well-being commonly referred to as a "runner's high," only dynorphin has the opposite effect.
"Like endorphins, dynorphins are opioid peptides, but endorphins make you feel good and dynorphins make you feel bad," Walker said. "So the theory I am investigating is that dynorphins are recruited during [alcohol] dependence and keep you in this really down, depressed, negative mood state.
"What I am trying to do is block those dynorphins, basically trying to block that down state so people don't have to excessively use drugs or alcohol."
Existing pharmaceutical options
There are currently three drug therapies approved by the U.S. Food and Drug Administration for the treatment of alcoholism.
Disulfiram, also known as Antabuse, works as a deterrent by causing a severe adverse physical reaction when the person taking it consumes alcohol.
Acamprosate reduces the physical distress and emotional discomfort people often experience when they stop drinking. This drug focuses on glutamate, one of the chemicals in the brain that transmits signals between neurons and cells, but according to Walker the precise way it works is still a subject of research.
The third FDA-approved drug therapy for alcoholism, Naltrexone, blocks the effects of endorphins, so drinking no longer produces an elevation in mood.
Walker believes his research will eventually lead to a fourth pharmacologic option.
Walker believes that a drug, or combination of drugs, that blocks the binding of dynorphin to its receptors can facilitate sustained recovery by easing the negative mood state that afflicts people when they stop drinking.
"In conjunction with those pharmacotherapies that target the other aspects of addiction and dependence, treatments can be designed that can assist an individual during those critical times that are likely to promote relapse," Walker said.
Academic and private research into new drug therapies is the precursor to clinical trials conducted by drug companies and the National Institutes of Health and upon which final FDA approval is based.
"I am on the pre-clinical side," said Walker. "You have to have a good idea, backed up by substantial evidence, before you get to the next step."
Behind the research
Walker's interest in alcohol and drug abuse treatment goes back to the 1980s, when he was a teenager growing up in the Hollywood Hills of Los Angeles. A number of friends and acquaintances got involved with drugs and alcohol. Some died as a result, and others never graduated from high school.
"It was very sad," said Walker. "I think that the initial impetus [for choosing this field of research] was to try and help people who are being plagued by this problem."
With this grant, Walker is in a position to do just that.
Walker's professional background
Walker received his doctorate in behavioral neuroscience from the University of California, Santa Barbara.
Following postdoctoral studies with George Koob in the Committee on the Neurobiology of Addictive Disorders at the Scripps Research Institute in La Jolla, Calif., he worked as a staff scientist in the institute's Department of Molecular and Integrative Neuroscience on topics related to alcohol dependence, negative affect, and adolescent alcohol exposure.
In 2008 Walker joined the psychology faculty at WSU, where he founded the Laboratory of Alcoholism and Addictions Neuroscience.
About the NIAAA
The National Institute on Alcohol Abuse and Alcoholism, an agency of the National Institutes of Health, supports and conducts biomedical and behavioral research on the causes, consequences, treatment, and prevention of alcoholism and alcohol-related problems.
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Relapse and Health Behavior Change
By Phyllis Shier, College of Liberal Arts
Katie Witkiewitz, assistant professor of psychology at WSU Vancouver, was awarded four grants this year to support her research developing behavioral treatments for smoking and alcohol use disorders, two of the leading causes of preventable death in the United States.
The grants, totaling more than $275,000, will be used to tackle adolescent alcohol and nicotine disorders and the factors that influence smoking and binge drinking among college students.
Witkiewitz uses empirically based models to track substance use and applies advanced quantitative research methods to better understand the complexities of addictive behavior. She will develop an intervention, for delivery via web-enabled mobile phones, aimed at reducing college smoking and binge drinking. Research funding will also allow her to further examine the predictors of alcohol use relapse and improve telephone counseling aimed at smoking cessation.
"The fundamental goal of my research and what I hope to achieve in my lifetime is to gain a precise understanding of why people return to a problematic behavior, such as substance use, heavy drinking, or poor diet, after a period of successful behavior change, such as abstinence, moderate drinking, healthy diet, and physical activity," she said.
Since 2003, Witkiewitz has received nearly $4 million in grants to support her research from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, the National Institute on Mental Health, and the National Cancer Institute.
"The process of health behavior change might be relatively constant across different behaviors," said Witkiewitz. "If we could understand why people fail at one behavior, we might be able to understand why people fail to change health behaviors in general. Then we could develop interventions that greatly improve the likelihood of successful behavior change."