07 Aug New Approach to Addiction: Diabetes Drug May Curb Cravings and Protect Brain White Matter

MedicalResearch.com Interview with:

Dr. Schmitz

Joy M. Schmitz, Ph.D.
Professor of Psychiatry Faillace Chair
McGovern Medical School
The University of Texas Health Science Center at Houston
Director, Center for Neurobehavioral Research on Addiction (CNRA)

Dr. Lane

Scott D. Lane Ph.D.
McGovern Medical School
Vice Chair For Research
Director Of Neurobehavioral Laboratory
Center For Neurobehavioral Research On Addiction
Director Of Research

University of Texas Health Science Center at Houston
Houston, TX 

MedicalResearch.com: What is the background for this study?

Response: Addiction science has made considerable progress in understanding how cocaine and other addictive drugs impair the brain. Over time, cocaine can disrupt brain regions that help us think, plan, solve problems, and exert self-control. These disruptions in brain structure can be seen in neuroimaging studies that reveal impairment in the nerve fibers or white matter (WM) tracts in the central and front parts of the brain. We conducted two systematic meta-analytic reviews of the literature to document the robustness of evidence showing alterations in WM integrity of chronic stimulant users relative to healthy control subjects who did not use cocaine or other drugs of abuse (Beard et al., 2019; Suchting et al., 2020). Importantly, WM impairments negatively predict treatment outcome, meaning individuals with greater levels of WM impairment are less likely to benefit from treatment and more likely to experience deficits in attention, working memory, and impulse control.

We reasoned that pharmacological interventions shown to protect WM integrity may help improve cognition and treatment outcomes in patients recovering from cocaine addiction. Pioglitazone, an approved medication for type 2 diabetes, has been shown to reduce inflammation and mediate protection after traumatic brain injury. The therapeutic potential of pioglitazone has prompted investigation of its role in neurodegenerative conditions, such as dementia, Alzheimer’s disease, and stroke. Similar to these brain diseases and injuries, pioglitazone might effectively protect the brain from the inflammatory damage created by cocaine use. 

MedicalResearch.com: What are the main findings?

Response: Our initial proof-of-concept study tested whether pioglitazone treatment would change brain WM integrity in persons with cocaine use disorder. In a sample of 30 participants, half received pioglitazone for 12 weeks of treatment and the other half received placebo. Diffusion tensor imaging (DTI) brain scans were performed on all participants before and after treatment.

There were 3 main findings:

• First, those who received 45 mg of pioglitazone showed significant improvement in brain WM integrity as shown by increased fractional anisotropy values at the end of treatment compared to those who received placebo.
• Second, pioglitazone treatment was associated with decreased craving for cocaine
• Third, pioglitazone was well-tolerated with good compliance and no serious adverse events. 

MedicalResearch.com: What should readers take away from your report?

Response: We think this research points to a new direction in medication development for the treatment of cocaine use disorder, and possibly other stimulants like methamphetamine. This direction shifts the focus to brain recovery by testing novel medications that have cognitive-enhancing effects. To the extent that medications like pioglitazone work by improving key neural and cognitive functions in the brain, patients may be more likely to benefit from therapy and achieve sustained abstinence.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Our results demonstrated “target engagement” or the ability of pioglitazone to improve WM integrity in the brains of individuals with cocaine use disorder. The next step is to determine whether these brain changes are associated with improvement in clinical outcomes such as reduced cocaine use and enhanced cognitive functioning. Future research might pursue this medication development approach for other addictive drugs, including methamphetamine – now one of the most abused illicit drugs, and also capable of causing significant structural and functional changes in the brain.

MedicalResearch.com: Is there anything else you would like to add? 

Response:      We are grateful to the National Institute on Drug Abuse (NIDA) for their interest and support of this research (R01 DA048026). For more information and to refer individuals for participation in a pioglitazone clinical trial, please visit: cnraclinic.com/2step

Citation:

Schmitz, J. M., Green, C. E., Hasan, K. M., Vincent, J., Suchting, R., Weaver, M. F., Moeller, F. G., Narayana, P. A., Cunningham, K. A., Dineley, K. T., and Lane, S. D. (2017) PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder: a double-blind randomized controlled pilot trial. Addiction, 112: 1861– 1868. doi: 10.1111/add.13868. 

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Last Updated on August 9, 2021 by Marie Benz MD FAAD