# Opioid/benzodiazepine polydrug abuse: Integrating research on mechanisms, treatment and policies

> **NIH NIH R33** · WAYNE STATE UNIVERSITY · 2021 · $655,159

## Abstract

PROJECT SUMMARY / ABSTRACT
Significance: Benzodiazepine (BZD)/opioid polysubstance abuse (PSA) confers significant risks of overdose,
disability and death; yet, little is known about phenotypes that could be targeted to decrease these risks. We
will address this multi-faceted problem at population, clinical and human laboratory levels of analysis, using the
integrative and translational focus of PAR-16-291. This project’s unifying hypothesis is that BZD/opioid PSA
is maintained by a dual-deficit in affective regulation (phenotypes: high anxiety-sensitivity/distress-intolerance
and hedonic deficit/reinforcement pathology, building on Koob’s reward-deficit/stress-surfeit model), associated
with impaired neurocognitive and behavioral functions, relative to BZD or opioid use alone. Goals: Our
interdisciplinary team (experts in epidemiology, biostatistics, clinical assessment, and human behavioral
pharmacology) will use rigorous and complementary mixed methods to test our unifying hypothesis in this
sequential R21/R33 approach. Aim 1 (R21): Determine from behavioral health treatment records the
prevalence of patient presentation with opioid, BZD or BZD/opioid PSA and associations of substance-use
patterns with affective symptoms (primarily anxiety and depression), physical comorbidities (primarily chronic
pain), medications, demographics, and treatment outcomes. This analysis will provide a context for assessing
generalizability of findings from Aim 2 (in-depth clinical assessment) and Aim 3 (human laboratory). Aim 2
(R21): In a sample of newly admitted behavioral health patients, rigorously evaluate and characterize deficits
across domains (affective, neurocognitive, behavioral) in opioid, BZD and BZD/opioid PSA and pattern of
substance use (especially simultaneous vs concurrent BZD/opioid PSA, alcohol use). Aim 3 (R33): Among
community-recruited research volunteers (non-treatment seekers) with a recent history of BZD/opioid PSA, test
whether: (3a) substance abuse severity among BZD/opioid PSA influences affective, neurocognitive and
behavioral measures (using the refined assessment battery from Aim 2) including more lifetime drug-use
consequences, and greater price-inelasticity for opioid and BZD using behavioral economic simulations; and
(3b) experimental drug administration of alprazolam/morphine vs. either drug alone or placebo (with dose-
response evaluation) will differentially alter affective/hedonic phenotypes in three different behavioral choice
procedures: (i) increase price-elasticity of drug demand, (ii) shift preference away from avoiding aversive
stimulation toward positive reinforcement, and (iii) increase monetary delay discounting. Overall impact: This
multi-level, integrated approach will test our unifying hypothesis that BZD/opioid PSA is maintained by a dual-
deficit in affective/hedonic regulation, with related neurocognitive and behavioral impairments. By translating
findings from population and clinical levels to laboratory-bas...

## Key facts

- **NIH application ID:** 10443186
- **Project number:** 4R33DA044946-03
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** CYNTHIA L ARFKEN
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $655,159
- **Award type:** 4N
- **Project period:** 2018-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443186

## Citation

> US National Institutes of Health, RePORTER application 10443186, Opioid/benzodiazepine polydrug abuse: Integrating research on mechanisms, treatment and policies (4R33DA044946-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10443186. Licensed CC0.

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