Project Summary:
The United States is in the midst of an opioid overdose epidemic with devastating societal effects. Following a progressive surge in overdose deaths from 2000 to 2017, there was a slight decline in 2018, followed by a resurgence in deaths since the COVID-19 pandemic. According to the Wisconsin Department of Health Services, Wisconsin led the estimated proportion of drug misuse for 2022 in the United States. In particular, the Milwaukee County incidence of overdose deaths was twice than the rest of Wisconsin and among the highest in the U.S. Moreover, the county ranked eighth nationally in per capita opioid overdose fatality rates in 2022 (U.S. Centers for Disease Control).
Epidemiological studies indicate that experiencing a life-threatening event induces post-traumatic stress disorder (PTSD) in a subpopulation of people. In the U.S., about six per 100 people have PTSD, according to the U.S. Department of Veterans Affairs. A diagnosis of PTSD substantially increases the likelihood of developing substance use disorder (SUDs), resulting in a 30-50% comorbid SUDs/PTSD4-9. Similarly, 30-60% of women seeking treatment for SUDs have a comorbid diagnosis for PTSD. Strikingly, women meet diagnostic criteria for PTSD at twice the rate of men, posing possible sex differences. Patients with comorbid PTSD/SUDs have greater drug use severity and have worse treatment outcomes than patients diagnosed with PTSD or SUDs alone. Opioids are among the most widely used drug, particularly in those suffering from PTSD. Clinical studies indicate opioids are used to self-medicate as a coping mechanism for anxiety and PTSD symptoms. These clinical findings strongly indicate that to alleviate comorbid PTSD and opioid use, there is a need for greater understanding of how the brain is altered by stress and opioid use.
This project seeks to enhance the understanding of the peripheral and central adaptations produced by acute stress, opioid use, and comorbid opioid use/PTSD in an effort to improve rational drug design.
By identifying specific peripheral and central neuroadaptive mechanisms in stress and opioid use, the researchers expect to identify new potential targets for regulating stress and opioid use and uncover novel markers that can improve precision medicine.