Breaking the Grip of Addiction

07/29/2009

“When I came out of college, as a Chemistry major with a heavy focus in organic chemistry,” says Ashley Kennedy, a fourth year graduate student in the Molecular and Systems Pharmacology (MSP) program, “I was primarily interested in the research and development side of pharmacology – I wanted to learn how to synthesize novel compounds and apply them in the field of medicine.  But then laboratory rotations and early graduate training exposed me to the broader fields of pharmacology, and my interests changed a bit.”  Ashley became interested in drug addiction – as a scourge that ruins so many individual lives, and as a problem for medical science to understand and better treat.  She supplemented her biomedical science training with a Master’s degree in Clinical Research, developing the expertise and skills to assess the clinical effects of new and proposed treatments for drug addiction.

Now, she is part of a clinical team that researches new treatment strategies to combat crack cocaine addiction by examining whether a medication that promotes therapeutic learning and memory can help sever the pathological learned associations involved in drug addiction.

Neural Mechanisms of Treating Drug Addiction

The research looks at a medication that is used in the treatment of fear- and anxiety-related disorders to help extinguish learned fear associations, namely D-Cycloserine, a partial agonist at the N-methyl-D-aspartate glutamate receptor.  The goal is to use the facilitating effects of D-Cycloserine on therapeutic learning and memory as an adjunct to cognitive behavioral therapy (CBT), to break the association between conditioned drug use cues and relapse behavior. “We’re interested in clinical outcomes like whether taking this medication can help addicts maintain abstinence and stay in treatment,” says Ashley.  “But we are also interested in the neural mechanisms underlying these outcomes, and how this medication may be affecting them.”

One part of investigating this is to ask patients to perform a cognitive test that assesses the level of attentional bias for drug cues or stimuli to provide a measure of their risk for relapse.  Subjects perform this task while receiving an MRI scan that reveals how their brain is functioning during this exercise. The test is referred to as a “Stroop task.”  In its simplest version, the Stroop task asks subjects to look at a sequence of ‘color’ words printed in various colors, and to identify the color that the words are printed in.  For example, seeing the images to the left, one would answer “red, green.”  That test measures the subject’s ability to ignore the non-target stimulus attribute (e.g., word meaning) and focus his or her attention on the target stimulus attribute (e.g., word color).  In a modified version that Ashley uses, patients are presented with a series of personal cocaine-related words and asked to count the number of words.  Here, the task measures the subjects ability to ignore the associations related to the addiction, or their attentional bias for drug-related stimuli.

“In neural terms,” explains Ashley, “we should see the levels of activity in different regions of the brain change as a function of time in treatment and treatment response.”  At the start of treatment, the dorsal striatum, a region of the brain involved with habit learning, should be very active, reflecting the strength of drug addiction memories.  As treatment progresses, activity should shift to the prefrontal cortex, a region involved in conscious control and decision-making.  “By examining these neural mechanisms, we hope to understand how D-Cycloserine combined with CBT may facilitate therapeutic learning and memory in the brain and how we might help to disrupt drug addiction memories using medications that intervene in very targeted ways.”

A Broad Perspective

Combining two programs – the MSP biomedical science program and the MS in Clinical Research program – has added an additional year to Ashley’s course of study, but has also enabled her to gain both a deeper knowledge of pharmacology and neuroscience and the specific skills and ethics related to applying these sciences to clinical populations.

Its multidisciplinary nature is part of what makes the work so interesting to Ashley.  “On the one hand, we are constantly engaged in the clinical trial aspects – recruiting potential candidates for inclusion, assessing whether their profiles fit the parameters of the study, and working through the collection of data.  On the other hand, we’re connecting this clinical research to detailed neuroscience related to decision-making and motivation and the pharmacological practice of medication development.  That broad span, and connecting those pieces, makes working on this study fascinating.”

The clinical aspect also brings contact with the very people the science aims to help – patients addicted to drugs.  Ashley works at the VA Hospital, with patients who are generally long-time addicts whose lives have been seriously impacted by drug addiction, often to the point where they are homeless and very much alone.  “Seeing the patients on a regular basis gives you a sense of grounding, a real understanding of who you are trying to help.  They don’t fit the stereotypes of drug addicts, but come from all kinds of backgrounds and walks of life.”

Ashley has found that her program at Emory encourages this broader view, both of the additional science training and of the possible professional pathways it may lead to – work as academic scientist, but also work in government, patent law, industry, and other pertinent areas.  “It’s a demanding course of study, with long and busy days,” says Ashley.  “But it is also a very supportive environment and deeply rewarding work.”