Physiological stress reactivity’s role in post-stress modulation of the drug cue-elicited late positive potential in Cannabis Use Disorder

Rates of daily cannabis use and Cannabis Use Disorder (CUD) are increasing in the United States. To inform risk prediction and treatment development efforts, it is imperative to identify reliable neurobiological markers of CUD severity in at-risk populations such as regular cannabis users. Prominent addiction theories suggest that stress potentiation of drug cue incentive salience is a central feature of disordered vs. recreational drug use, which has been corroborated using a neurophysiological index of drug cue incentive salience (i.e., the late positive potential [LPP]) in cannabis users. However, the mechanism through which acute stress potentiates the cannabis LPP in CUD is unclear. To address this gap, cannabis LPPs were measured in 102 cannabis users before and after a stress induction. Physiological [hypothalamic- pituitary-adrenal (HPA) axis, heart rate, skin conductance] and subjective stress reactivity were also measured. An additional cannabis user control group (n=52) completed a single lab visit with a non-stressful task to validate the stress induction. Based on prior work, we hypothesized that cortisol stress reactivity would predict post-stress cannabis LPP enhancement in more severe CUD. The hypothesis was supported and specific to HPA-axis vs. autonomic or subjective stress reactivity. Acute stress potentiation of the cannabis LPP, likely via HPA-axis activation, may be a biomarker of heavy/disordered cannabis use in regular users.