Richard Macatee

Research topics

Matched from this investigator's NIH project titles and abstracts.

• Emotion and Affective Neuroscience
• Depression
• Neuroimaging

Active NIH awards

• Refinement and Pilot Testing of a Computerized Distress Tolerance Intervention with Just-In-Time Text Message Reminders for Cannabis Use Disorder

  7R34DA057733-04

  NIDA · FY 2025 · $197K

  Project Summary. The prevalence of daily cannabis use and Cannabis Use Disorder (CUD) has increased in the United States over the past two decades. Brief, computerized harm reduction interventions that target specific high-risk CUD populations could be an efficient approach to reducing CUD. Distress intolerance (DI), which refers to the tendency to negatively appraise and escape aversive emotional states, is a risk factor associated with stress-related cannabis use motivation and CUD severity/chronicity. Thus, a brief, accessible, low-cost intervention that reduces DI in those with CUD and elevated DI could have a significant public health impact. This proposed Stage I project aims to modify an existing two-session computerized distress tolerance intervention to optimize emotion regulation learning/generalization and test its impact on DI and cannabis use outcomes in a randomized controlled trial. Specifically, the intervention will be condensed to one-session and its imaginal exposure module will be modified to shape emotional engagement with the aim of maximizing within-session habituation, which will be signaled with a novel audio/visual cue (habituation cue). Habituation cues will then be delivered in just-in-time text message reminders triggered by naturalistic distress reported via ecological momentary assessment. After obtaining feedback on the modified Emotional Engagement Distress Tolerance Intervention in a small sample (Specific Aim 1), the intervention’s efficacy compared to a stringent, credible, time-matched health education control intervention will be tested in a randomized controlled trial in 80 cannabis users with CUD and high DI. To measure the intervention’s mechanistic target engagement (Specific Aim 2), multi-method DI assessments will be administered through four-month follow-up. To measure the intervention’s impact on cannabis use (Specific Aim 3a), stress-related cannabis use motivation (lab stress- elicited craving and neurophysiological drug cue reactivity, ecological momentary assessment of stress-elicited cannabis use) will be assessed through the intervention period. Interviewer-assessed cannabis use frequency, CUD severity, and urinary THC metabolite concentration will be measured through 4-month follow-up. Quality of life and anxiety/depression symptoms will also be measured as secondary outcomes through 4-month follow-up (Specific Aim 3b). As an exploratory aim, a wristworn device will be used to measure ambulatory physiology during a portion of the intervention period to evaluate the feasibility of detecting heightened real- world distress based on objective indicators (Specific Aim 4).Our central hypothesis is that, compared to a control intervention, the Emotional Engagement Distress Tolerance Intervention will produce superior reductions in multi-method assessments of DI, stress-related cannabis use motivation, disordered cannabis use, and psychosocial functioning. Successful completion of the proposed aims will (1) justify a subsequent Stage II trial, and (2) inform efforts to integrate the just-in-time habituation reminders with wearable technology in order to increase emotion regulation generalization opportunities and decrease participant report burden.

• Experimental evaluation of the mechanisms driving acute stress potentiation of drug cue reactivity in Cannabis Use Disorder

  7R21DA058780-03

  NIDA · FY 2025 · $151K

  Project Summary. The prevalence of daily cannabis use and cannabis use disorder (CUD) has increased in the United States over the past two decades. Unfortunately, psychosocial treatments produce minimal long- term abstinence rates and no FDA-approved medications for CUD exist. Thus, identifying novel CUD treatment targets is an increasingly urgent public health need. Stress-elicited cannabis use motivation has been implicated in worse CUD outcomes, but a mechanistic understanding of how acute stress increases cannabis use motivation in CUD is limited. The PI’s work has demonstrated that acute psychosocial stress enhancement of subsequent cannabis cue incentive salience, as indexed by the late positive potential (neural measure of approach-motivated attention recorded using electroencephalography [EEG]), was associated with worse CUD severity and intervention response, independent of subjective craving. Moreover, hypothalamic pituitary adrenal [HPA]-axis, rather than noradrenergic or subjective reactivity to the psychosocial stressor was associated with subsequent potentiation of the cannabis cue-elicited late positive potential. These studies suggest that non-genomic, rapid glucocorticoid effects may be a contributing mechanism in stress amplification of neural drug-cue reactivity, but their correlational designs preclude causal inference. Further, psychosocial stressors are unable to isolate HPA-axis vs. noradrenergic components of stress reactivity. To isolate HPA- axis activation and test causality, pharmacological manipulations, common in animal models but rare in human studies, will be used to produce separate and co-operative glucocorticoid (hydrocortisone) and noradrenergic (yohimbine) activation. We will employ a 2x2 randomized, placebo-controlled double-blind crossover design in 36 cannabis users with severe CUD. Our primary aim is to test the causal potentiating effect of glucocorticoids on neural drug-cue reactivity, and further determine if the effect depends on co-occurring noradrenergic stimulation. Preclinical work indicates that glucocorticoids can potentiate reward motivation via mobilization of endocannabinoid activity (primary target of cannabis). Thus, as an exploratory aim in line with NIDA priorities (NOT-DA-22-048), we will obtain plasma samples to test the impact of pharmacological stress on circulating endocannabinoids and their mediating role in glucocorticoid potentiation of neural drug-cue reactivity. This project represents a highly novel integration of a rigorous pharmacological challenge design with biological markers of drug-cue incentive salience and endocannabinoid system activity. If hypotheses are confirmed, one causal mechanism through which stress increases neural cannabis cue reactivity will be known, which has immediate implications for testing experimental therapeutics. The long-term goal is to understand how a stress- related mechanism predictive of worse CUD phenotype is generated and can be blocked in CUD. Development of this model will provide a valid, efficient and (relative to other neuroimaging methods) low-cost approach to screen candidate medications and optimize psychosocial drug cue exposure therapies.