Center for the Study of Alcohol Use Disorder & Traumatic Stress

Our researchers at the Center for the Study of Alcohol Use Disorder and Traumatic Stress in NYU Langone’s Department of Psychiatry are striving to better understand the relationship between these two comorbid conditions. We also work to develop effective treatments for patients who have an alcohol use disorder and simultaneously suffer from post-traumatic stress.

Under the guidance of Charles R. Marmar, MD, center director, our researchers use advanced and novel computational methods, biomarker analysis, and imaging approaches to further their knowledge. The center was established in 2019 thanks to a generous five-year grant from the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.

Alcohol use disorder affects about a third of individuals in the United States at some point in their lives. Post-traumatic stress disorder (PTSD) is one of the most common psychiatric comorbidities of alcohol use disorder, especially among veterans. The symptoms of PTSD interact with those of alcohol use disorder in a self-exacerbating cycle.

Our researchers study treatments that may address both conditions at once, with the anticipation that this approach is likely more effective than treating each disorder separately. Researchers recruit participants from a variety of facilities and programs in the New York City metropolitan area, including NYU Langone’s Steven and Alexandra Cohen Veterans Center for the Study of Post-Traumatic Stress and Traumatic Brain Injury and the Steven A. Cohen Military Family Center; local U.S. Department of Veterans Affairs medical centers, including the VA NY Harbor Healthcare System; psychiatric care and detox clinics at NYC Health + Hospitals/Bellevue; and an outpatient psychiatry clinic at NYU Langone Hospital—Brooklyn.

Learn more about our current research projects via the descriptions below.

Topiramate for the Treatment of Alcohol Use Disorder and Post-Traumatic Stress Disorder

Michael P. Bogenschutz, MD, and Joshua D. Lee, MD, are leading a phase II, double-blind, two-group randomized, controlled trial comparing topiramate with placebo in individuals with alcohol use disorder and PTSD. Topiramate is an anticonvulsant with properties that may be beneficial for simultaneously treating both conditions. Investigators are comparing 100 subjects receiving topiramate at a maximum dosage of 200 mg/day for 12 weeks with 50 subjects receiving placebo.

Research goals are to assess the safety and feasibility of administering topiramate in a population with alcohol use disorder and PTSD; to determine the effects of topiramate and rs2832407 genotypes on alcohol use outcomes in these patients; to understand, using sophisticated neuroimaging procedures, who responds to topiramate and by what mechanism; to determine any differences in blood and imaging biomarkers between topiramate and placebo groups; and, to advance personalized medicine by combining clinical, neurocognitive, genetic, plasma, and imaging markers from clinical trial participants using multivariate prediction of topiramate response.

For further study details and eligibility criteria, please view full clinical trial information. This study involves collaboration among several groups on our team.

If you are a patient who is interested in enrolling in this trial, please contact Lindsay Rosenthal, clinical research coordinator, at lindsay.rosenthal@nyulangone.org or 646-501-9684.

Grant: Topiramate as a Treatment for Co-occurring Alcohol Use Disorder Comorbid with Post-Traumatic Stress Disorder; 1P01AA027057-01

Neuroimaging Procedures

Neuroimaging researchers led by Dr. Marmar and Amit Etkin MD, PhD, are employing functional MRI (fMRI) to better understand which subjects respond to topiramate, specifically by using fMRI tasks to assess emotional reactivity and regulation to general negative stimuli and reactivity to alcohol cues. We complement this by mapping the same brain circuits at the neurophysiological level using concurrent transcranial magnetic stimulation and transcranial magnetic stimulation with electroencephalography.

The latter approach allows researchers to causally measure neuronal temporal scale excitation-related and inhibition-related neurophysiological responses to brain circuit–targeted neurostimulation, with source-localized electroencephalographic responses drawn from the same cortical structures investigated with fMRI tasks. Neuroimaging procedures are conducted after randomization and in week 14, the last week of treatment. One transcranial magnetic stimulation with electroencephalogram recording is also taken at week 7.

Blood Biomarker Core

Led by Charles R. Marmar, MD, the Blood Biomarker Core fosters synergistic and coordinated multidisciplinary research on clinically relevant blood, plasma, and brain biomarkers, enabling the translation of findings from preclinical and clinical projects. The goal is to better understand the neurobiological mechanisms of action of topiramate and to predict its effects in dual-diagnosis alcohol use disorder and PTSD.

We collect blood from all clinical trial participants before and after randomization. Researchers use Simoa® and enzyme-linked immunosorbent assays to determine blood concentrations of molecules belonging to pathways involved in stress response and alcohol reinforcing and motivational actions. These are excitatory and inhibitory amino acids altered in alcohol use disorder, PTSD, and coexisting disorders, and central to the possible topiramate mechanisms of action; peptides and hormones regulating hypothalamic pituitary adrenal axis responses; biomarkers implicated in neuroinflammation; and markers of apoptosis, oxidative stress, and mitochondrial dysfunction.

Core researchers are also banking participants’ plasma, serum, and whole blood; DNA; and RNA for future systems biology analyses. In addition, blood biomarkers from the clinical trial are being compared with imaging markers.

Analytics and Biostatistics Core

Led by Eugene M. Laska, PhD, and Carole Siegel, PhD, the Analytics and Biostatistics Core is responsible for managing and analyzing clinical trial data. Our researchers apply advanced statistical analyses in hypothesis testing and machine learning to estimate individualized predictions of response to topiramate. They integrate findings across projects by determining the relationships of blood and imaging markers in clinical trial participants. Our scientists also developing novel computational approaches to data analysis based on biomarkers predictive of treatment response and a causal approach to predicting individual outcomes.

Administrative Core

Our center’s Administrative Core makes many contributions as well, such as providing governance, infrastructure, budgeting, and financial accountability; planning meetings and completing administrative tasks for all component research projects and cores; promoting interactions and collaborations among the cores; and ensuring compliance with National Institutes of Health policy requirements.

Cannabidiol as a Treatment for Alcohol Use Disorder Comorbid with Post-Traumatic Stress Disorder

Cannabidiol is a promising candidate for the reduction of stress-induced craving by inhibiting extended amygdala output. The phytocannabinoid also has potential antiaddictive, traumatic- and addictive-memory modifying, as well as procognitive, effects, making it a potential integrated treatment for both alcohol use disorder and PTSD. Cannabidiol also has a lack of intoxicating effects and a low potential for abuse.

In this first-of-its-kind double-blind, randomized, proof-of-concept study, our researchers under the leadership of Dr. Marmar, Michael P. Bogenschutz, MD, and Esther Blessing, MD, PhD, are comparing alcohol use and PTSD symptoms in 30 participants taking cannabidiol 600 mg/day for 6 weeks with those in 18 subjects taking placebo. Researchers are also assessing the safety of cannabidiol.

Safety measures, cognitive tasks, and psychomotor functions are assessed weekly throughout the study. Researchers evaluate the number of drinks participants consume each day using the Time Line Follow Back methodology. We assess PTSD symptoms using the PTSD Checklist for DSM-5 total score. Investigators also conduct human laboratory studies using traumatic stress–induced craving tasks.

We measure cannabidiol in the serum at baseline and at six weeks to assess the level at which therapeutic effects might occur and dose accumulation of the agent. In addition, investigators are determining whether cannabidiol metabolites convert to tetrahydrocannabinol in the serum and whether cannabidiol elevates anandamide serum levels.

Overall, we predict that, as compared with placebo, cannabidiol can result in greater reduction in subjective traumatic stress– and alcohol cue–induced craving and accompanying physiological stress response. For more study details, please view full clinical trial information.

Grant: Cannabidiol as a Treatment for Alcohol Use Disorder Comorbid with Post-Traumatic Stress Disorder; R21AA026424

Effects of Cannabidiol in Alcohol Use Disorder

Led by Michael P. Bogenschutz, MD, this double-blind, randomized, proof-of-concept study is designed to assess the feasibility and contrast effects of cannabidiol treatment to those of placebo on drinking-related outcomes in patients with alcohol use disorder. Researchers are evaluating the safety of extended daily cannabidiol, assessing the impact of cannabidiol on neuropsychological domains implicated in alcohol use disorder, and generating preliminary data on the impact of cannabidiol on alcohol consumption.

Following screening and baseline assessments, 40 participants are being randomized in a one-to-one ratio to receive either placebo or 600 mg oral cannabidiol per day for four weeks, immediately followed by 1200 mg oral cannabidiol per day for an additional four weeks, for eight weeks in total. For more study details, please view full clinical trial information.

Grant: Effects of cannabidiol in alcohol use disorder; 5R21AA025748-02

Faculty

Our center faculty are experts in the scientific investigation of comorbid alcohol use disorder and PTSD.

Charles R. Marmar, MD
Duna Abu-Amara, MPH
Esther Blessing, MD, PhD
Michael P. Bogenschutz, MD
Donald C. Goff, MD
Eugene M. Laska, PhD
John Rotrosen, MD
Arieh Y. Shalev, MD
Carole Siegel, PhD

Study Participation and Eligibility

To learn more about study eligibility and the recruitment process for our Center’s research projects, please contact Duna Abu-Amara, MPH, senior project manager, at duna.abu-amara@nyulangone.org.

Contact Us

For more information about our Center for the Study of Alcohol Use Disorder and Traumatic Stress, please contact Charles R. Marmar, MD, at charles.marmar@nyulangone.org.