# Nature and Predictors of Impaired Harm Avoidance in Polysubstance Abuse

> **NIH NIH R33** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $598,925

## Abstract

PROJECT SUMMARY/ABSTRACT
Opioid overdose, occurring as part of opioid mono-substance use (MSU) and, more intensely, among those
with poly-substance use (PSU), has reached an epidemic level in the United States, and is reflective of other
high-risk behaviors among those with PSU. Accordingly, there is an urgent public health need for improved
treatment and prevention strategies for these populations, as guided by findings on the etiology and nature of
both laboratory-assessed and clinical harm-avoidance deficits. Our purpose is to evaluate the nature and
significance of laboratory-assessed harm avoidance deficits in order to identify potential treatment targets
(mechanistic outcomes) that may underlie devastating, clinical harm-avoidance deficits, characterized by high
risk for blood-borne viruses, criminality, and repeated overdoses among those with opioid PSU relative to
MSU. In the animal model, we examine whether laboratory-assessed harm avoidance deficits (assessed via
drug self-administration punishment and subsequent operant avoidance paradigms) arise from pre-existing
inhibitory control deficits, drug use, or the combination of these factors, specifically evaluating differences in
harm-avoidance capacity in mono (heroin or cocaine) vs. poly (heroin + cocaine) substance use models. Our
subsequent work in humans will use two fear-based (acquisition of learned fear association, operant avoidance
of this association) and two monetary-based (Iowa Gambling Task and monetary choice) laboratory measures
of harm avoidance deficits to compare the severity of laboratory harm avoidance deficits in outpatients with
opioid MSU or opioid+stimulant PSU. We will use these measures to predict and understand the nature of
clinical harm-avoidance deficits in this sample of men and women. Close analogue procedures have been built
into the animal and human studies, with the human studies providing a quasi-experimental or associative
replication of the animal paradigms, i.e., allowing the tightly controlled experimental evidence (allowing causal
conclusions) from the animal phase to aid the design and interpretation of less controlled, predictive models in
the human stage.

## Key facts

- **NIH application ID:** 10331497
- **Project number:** 4R33DA045148-03
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Kathleen M. Kantak
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $598,925
- **Award type:** 4N
- **Project period:** 2018-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331497

## Citation

> US National Institutes of Health, RePORTER application 10331497, Nature and Predictors of Impaired Harm Avoidance in Polysubstance Abuse (4R33DA045148-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10331497. Licensed CC0.

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