Dr. Charles Marmar presents research.
Photo: Karsten Moran
Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) are among the most common and debilitating psychiatric ailments in the United States.
The two disorders are highly comorbid, with studies suggesting that 30 percent to 60 percent of individuals diagnosed with AUD have PTSD and 20 percent to 70 percent of individuals diagnosed with PTSD have AUD. One disorder appears to exacerbate the other, leading to higher mortality and impairment and to poorer response to treatment.
Although several medications have been tested for AUD efficacy in patients with AUD/PTSD, none have progressed to a phase III trial.
Study Looks At Cannabidiol As New Treatment Option
In September 2017, researchers at Ƶ received a grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) to investigate a promising new therapy for AUD in patients with PTSD: cannabidiol (CBD), one of the main chemical components of marijuana. CBD has been shown in animal and human trials to produce anxiolytic, anti-addictive, anti-inflammatory, and fear-extinction effects, with no evidence of toxicity.
Intriguingly, threat-related amygdala arousal, a predictor of alcohol craving in PTSD patients, appears to be reduced by CBD, without the euphoria-inducing effects of marijuana’s other main active ingredient, tetrahydrocannabinol (THC). Preclinical data suggest that CBD may also have longer-term effects in reducing alcohol craving, possibly related to increased hippocampal neurogenesis.
“This is a remarkably complex drug with multiple actions affecting the brain and behavior,” says the study’s principal investigator, Charles R. Marmar, MD, the Lucius N. Littauer Professor of Psychiatry, chair of the , and director of the Steven and Alexandra Cohen Veterans Center for the Study of Post-Traumatic Stress and Traumatic Brain Injury.
Dr. Marmar’s double-blind study comparing CBD with placebo in 40 veterans and civilians with PTSD and AUD will be the first of its kind to explore the effects of CBD on subjects diagnosed with both disorders. Safety and tolerability, alcohol use and craving, and PTSD symptoms will be assessed at baseline and over six weeks of treatment. In another first of its kind NIAAA-funded study, principal investigator Michael P. Bogenschutz, MD, professor of psychiatry, will investigate the effects of CBD on patients with AUD alone.
Beyond CBD’s potential effects on PTSD and AUD, Dr. Marmar notes, the drug also shows promise against neuropsychiatric disorders ranging from social anxiety and schizophrenia to epilepsy. “It’s hard to think of another drug with as much potential across such a diverse array of neuropsychiatric problems,” he says. “If CBD proves to be as good as it looks, it could be analogous to a steroid or a broad-spectrum antibiotic.”
Ƶ will also be conducting research using CBD to treat PTSD and traumatic brain injury, thanks to a generous grant from the Bank of America, received in 2017.
Advancing PTSD Biomarkers
Before PTSD can be treated, it must be diagnosed—a process that is not always easy. Military veterans and other first responders often underreport symptoms because of perceived stigma; in cases involving litigation, some individuals may exaggerate symptoms in pursuit of financial compensation. Thus, to improve diagnostic accuracy and precision, researchers around the world are searching for the disorder’s biological markers.
Dr. Marmar is helping to spearhead these efforts as a principal investigator in the PTSD Systems Biology Consortium, a U.S. Department of Defense–funded collaboration involving seven academic and military research centers.
Over the past five years, the consortium has collected blood and urine samples, anthropometric data, brain images, and cognitive assessments of 166 male combat veterans of the wars in Iraq and Afghanistan—83 subjects with PTSD and 83 healthy controls.
The evidence is being analyzed by specialists in genetics, genomics, metabolomics, proteomics, neurobiology, and other disciplines, aided by experts in complex computation.
“We have more than 1 million biological features on each subject,” says Dr. Marmar, who heads the project’s clinical and neurocognitive phenotype core, “so it should be no surprise that the informatics is extremely challenging.”
The researchers have found several promising biomarkers, and initial candidates are expected to be submitted for FDA review in two to three years. Beyond their potential utility in screening and diagnosis, such markers may someday help to identify individuals at higher risk of PTSD, as well as to identify biological factors contributing to resilience, which could lead to rapid screening before, during, and after deployments and to new treatment targets.
New App Searches For PTSD In Voice Patterns
One key biomarker for PTSD may be alterations in vocal patterns. In 2017, Dr. Marmar and his colleagues completed the first study to test whether an automated, speech-based assessment can objectively identify PTSD in combat veterans.
The researchers worked with speech recognition engineers at SRI International in Menlo Park, California—the company that contributed to Apple’s Siri platform— using machine learning to analyze voice recordings of 56 veterans with PTSD and -81 healthy controls. Examining more than 40,000 features—including patterns of pitch, volume, rhythm, and intensity—the team found approximately 200 that distinguished subjects with PTSD from controls.
Once these findings are replicated and refined, they could enable the creation of smartphone apps to help screen for PTSD or clarify its diagnosis. “We’re looking for the vocal equivalent of a fingerprint,” says Dr. Marmar. “In the future, we believe that mental health providers will use vocal analysis in combination with other noninvasive clinical tests to assess many neuropsychiatric disorders more quickly, reliably, and cheaply than is currently possible.”
