# Cue Incubation in Substance Use Disorders: Validation and Assessment of Mechanisms

> **NIH NIH R21** · UNIV OF MARYLAND, COLLEGE PARK · 2022 · $193,125

## Abstract

PROJECT SUMMARY
Substance cue-reactivity is a central process underlying patterns of substance use. Because it is associated with
relapse, it is an important target for interventions. Mechanistic research in rats indicates that reactivity to drug
cues increases across the first month of abstinence, often referred to as cue incubation. Cue incubation has
recently been demonstrated in several studies with humans, with cigarette, alcohol, methamphetamine, and
cocaine use. Importantly, the degree of cue incubation varies between individuals, and has been related to risk
of relapse in rat models. Thus, cue incubation may represent a critical process indexing vulnerabilities to relapse
for humans in the early stages of drug use cessation. Further work is needed to assess this important source of
variance in cue-reactivity with humans, and develop novel targets for intervention during this vulnerable period.
Approach. In this study we will test for cue incubation in a sample of inpatients with cocaine use disorder in a
residential drug-rehabilitation center. Primary measures of incubation will include self-report measures of
craving, EEG-based late positive potential (LPP; indexing attentional engagement), and blood-based brain
derived neurotrophic factor (BDNF; a well-validated measure of cue incubation in rats, indexing negative valence
system engagement). We will include additional measures of candidate mechanisms underlying cue incubation
based on the Research Domain Criteria (RDoC) framework, including control (executive function), arousal, and
positive and negative valence systems (e.g. reward and loss processing, response inhibition and execution, and
affective image processing). Goal. The proposed work will examine cue incubation in humans with cocaine use
disorder. We will measure incubation at subjective, behavioral, neural, and biochemical levels, and include
sufficient numbers of participants to examine predictors of incubation across individuals. These studies will
provide a critical bridge between animal and human studies of incubation, and novel, comprehensive, information
about candidate processes underlying cue incubation in humans – with the goal of advancing the utility of the
cue incubation hypothesis in etiologic and intervention work with humans.

## Key facts

- **NIH application ID:** 10397679
- **Project number:** 5R21DA053359-02
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Edward M. Bernat
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $193,125
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397679

## Citation

> US National Institutes of Health, RePORTER application 10397679, Cue Incubation in Substance Use Disorders: Validation and Assessment of Mechanisms (5R21DA053359-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10397679. Licensed CC0.

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