Cumulative Effect of ACEs on the Neurocircuitry of Drug Withdrawal

$208,403P20FY2025GMNIH

Osu Center For Health Sciences, Tulsa OK

Investigators

Linked publications & trials

Paper 39583988 Paper 39385098 Paper 39340496 Paper 38915228 Paper 38878049 Paper 38468697 Paper 38371174 Paper 38165585 Paper 37976009 Paper 37975709 Paper 37949633 Paper 37889252 Paper 37562704 Paper 37324057 Paper 36912502 Paper 36727632 Paper 36401128 Paper 36113375 Paper 36036330 Paper 35908297 Paper 35859781 Paper 35819014 Paper 35553373 Paper 35113318 Paper 35113308 Paper 34958975 Paper 34820951 Paper 34710334 Paper 34469264 Paper 34468973 Paper 34346003 Paper 34328346 Paper 34304270 Paper 34291820 Paper 33955346 Paper 33860552 Paper 33858395 Paper 33778769 Paper 33763501 Paper 33734789 Paper 33706023 Paper 33665605 Paper 33650766 Paper 33622505 Paper 33620662 Paper 33400442 Paper 33123807 Paper 33104783 Paper 33101704 Paper 33032071 Paper 32782346 Paper 32511674 Paper 32185847 Paper 32131371 Paper 32112095 Paper 31766006 Paper 31540673 Paper 31417321 Paper 31368725 Paper 31324842 Paper 31271303 Paper 31109265 Paper 30450956 Paper 29460349

Abstract

The proposed project examines how cumulative Adverse Childhood Experiences (ACEs) influence the brain mechanisms underlying nicotine withdrawal symptoms, specifically cognitive control and craving sensations, in users of Electronic Nicotine Delivery Systems (ENDS). ACEs significantly increase vulnerability to addiction, contributing to earlier drug use initiation, heavier lifetime use, and more failed quit attempts. Two critical brain regions may underlie these effects: the prefrontal cortex (PFC), essential for cognitive control and resisting cravings, and the mid-insular cortex (dmIC), crucial for sensing internal bodily states associated with withdrawal. Forty-six adult ENDS users (aged 18-50) with varied histories of childhood adversity (1-10 ACEs) will participate in this two-week study. Participants will exclusively use provided ENDS devices that objectively measure daily nicotine intake. They will undergo two weekly fMRI sessionsâone following regular nicotine use and another after 24-hour abstinenceâto measure brain responses during cognitive control, interoceptive attention, and cue-reactivity tasks. Behavioral, subjective craving, and serum cotinine measures will complement imaging data. The current study aims to determine: 1) how ACEs influence patterns of nicotine use and withdrawal symptoms, such as craving intensity and diminished behavioral inhibition; 2) how ACEs impact neural mechanisms underlying altered craving (dmIC) and impaired behavioral inhibition (PFC) during nicotine abstinence. This research is innovative though integrating assessments of interoceptive and executive control systems in ENDS users with objective nicotine use measurements. Results will advance understanding of how childhood adversity potentiates nicotine dependence, providing critical insight to inform public health interventions targeted at improving treatments for substance use disorders.

View original record on NIH RePORTER →