Impact of a computerized distress intolerance intervention on electrocortical reactivity to cannabis and threat cues: A randomized controlled trial.

Abstract

Objective: Given increasing rates of daily cannabis use and Cannabis Use Disorder (CUD) in the United States, it is imperative to understand CUD mechanisms in high-risk groups. Cannabis users with high distress intolerance (DI) are at elevated risk for severe and chronic CUD, but neural mechanisms linking CUD and DI are unknown. Cross-sectional data suggests that acute stress modulation of the cannabis and threat cue-elicited late positive potential (LPP), a neurophysiological marker of motivated attention, are possible mechanisms. However, longitudinal research is needed to clarify the roles of these elicited LPPs in CUD maintenance. Method: Sixty cannabis users with high DI were randomized a brief computerized intervention targeting DI or a control intervention. Elicited LPPs were measured before and after a stressor at baseline and postintervention. Intervention effects on stress modulation of the cannabis and threat LPPs, as well as their prospective associations with CUD, were assessed. Results: Elicited LPPs did not significantly change in either intervention group. Acute stress enhancement of the cannabis LPP predicted more severe CUD and greater chronicity at 4-month follow-up. Conclusions: Cannabis and threat LPPs were not altered by a brief DI intervention despite improvement in DI and cannabis use outcomes. Given that acute stress enhancement of the cannabis LPP predicted poorer CUD outcome, it may be a fruitful intervention target in distress intolerant cannabis users. Public Health Significance StatementCannabis users with high distress intolerance are at heightened risk for Cannabis Use Disorder. This study demonstrates that a brief intervention for distress intolerant cannabis users did not affect the neurophysiological response to cannabis cues, but stress modulation of the cue-elicited response predicted worse intervention response. Stress modulation of cannabis cue reactivity may be a fruitful intervention target in this population.

A scoping review of electroencephalographic (EEG) markers for tracking neurophysiological changes and predicting outcomes in substance use disorder treatment

“…A study examining the effects of a distress-tolerance intervention (two sessions, one per week, 30 min psychoeducation, 30 min idiographic distress exposure) found no changes in cannabis and threat cue LPPs (Macatee et al, 2022 ). However, the study noted links between higher post-stressor cannabis cue LPP and greater severity/chronicity at 4-month followup (Macatee et al, 2022 ).…”

“…Overall, the current set of behavioral and pharmacological studies is small and heterogeneous, with some studies reporting lack of clear treatment effects (Martinez-Maldonado et al, 2020 ; Macatee et al, 2022 ), lack of mediation of clinical outcome variables by EEG metrics (Robinson et al, 2022 ), or no links between EEG metrics and clinical variables (Brown et al, 2020 ). Nevertheless, results showing decreases in higher frequency bands and increases in lower frequency bands with treatment, as well as higher LPP to pleasant cues predicting positive outcomes, are generally in agreement with the EEG-SUD literature reviewed above in previous sections.…”

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

“…Further, other measures of drug use motivation, including craving (Franken et al, 2003;Franken et al, 2008), cue-elicited emotional arousal (Franken et al, 2003), drug cue attention bias (Webber et al, 2022b), current vs. ex-user status (Littel & Franken, 2007), substance use frequency/quantity (Cheng et al, 2016;Dunning et al, 2011), and simulated drug choice behavior (Moeller et al, 2012), positively correlate with drug-cue elicited LPP amplitude, providing additional evidence of validity. Macatee and colleagues (2019) found a non-significant overall effect of acute stress on the cannabis LPP, but individual differences in stress modulation of the cannabis LPP were associated with concurrent CUD severity and CUD persistence through follow-up (Macatee et al, 2022). Neither subjective stress nor craving predicted stress potentiation of the cannabis LPP, suggesting that a conscious, explicit increase in expected value of cannabis for negative affect reduction did not account for CUD associations.…”

“…Only two studies known to the authors have tested acute stress modulation of neural cannabis cue reactivity in regular users (Macatee et al, 2019(Macatee et al, , 2022. Macatee and colleagues (2019) measured the late positive potential (LPP) to cannabis cues, an event-related potential recorded using electroencephalography (EEG), before and after an acute stress induction in regular cannabis users varying in CUD severity.…”

“…Secondarily, the control group allowed for an exploratory test of the core hypothesis's specificity to stress-elicited cortisol reactivity (as opposed to general cognitive task engagement). Based on our prior work (Macatee et al, 2019(Macatee et al, , 2022, theory (Berridge & Robinson, 2016;Johnston et al, 2016), and the HPA-axis's impact on dopamine/reward-seeking (e.g., Piazza et al, 1996), it was hypothesized that cortisol, but not heart rate, skin conductance, or subjective stress reactivity would predict subsequent enhancement of the cannabis LPP, and that this relationship would be moderated by CUD severity such that the positive association would only emerge in cannabis users with more severe CUD.…”