# A Clinical Laboratory with Integrated Neuroscience (CLIN) for Early Evaluation of Medications for Substance Use Disorders

> **NIH NIH UG1** · UNIVERSITY OF PENNSYLVANIA · 2021 · $165,354

## Abstract

The nation's grim opioid crisis surges on, with the fentanyls (high potency synthetic opioids) driving
unprecedented mortality rates. Drug overdose deaths are now the leading cause of death in those
under age 50, with more than 47,000 Americans dying of opioid overdose in 2017. As of December
2018, Philadelphia had the third highest rate of opioid overdose deaths in the country (out-ranked only
by Pittsburgh and Baltimore). Fentanyl is present in 84% of the fatal opioid overdoses in Philadelphia.
Medication-assisted treatment (MAT) for opioid use disorders – whether full opioid agonist
(methadone), partial opioid agonist (buprenorphine), or a full antagonist (naltrexone) – is critical for
reducing opioid use, and for preventing overdose deaths. Unfortunately, compliance with these life-
saving medications is often poor, with ancillary use of non-opioid drugs (especially cocaine) as a
common culprit. Cocaine is found in almost half of the opioid overdose deaths in Philadelphia.
 Identifying promising adjunctive medications that reduce cocaine and other illicit drug use
during MAT could improve adherence and save thousands of lives each year. Further, measuring
how these medications “engage” the intended brain targets will speed rational medication
development. Toward both these goals, we have established a Clinical Laboratory with Integrated
Neuroscience (CLIN) for Evaluation of Medications for Substance Use Disorders at the University of
Pennsylvania Center for Studies of Addiction.
 In the initial demonstration project for the UG1, we will test the promise of a dopamine D3-
preferring agent, cariprazine (Vraylar, 1.5 mg daily), vs. placebo both for (Aim 1) preliminary
clinical efficacy (reduced illicit drug use, and improved adherence to life-saving buprenorphine),
and (Aim 2) for target engagement (e.g., limbic activation by opioid and cocaine cues), in patients
with both opioid use disorder (OUD) and cocaine use disorder (CocUD), in an 8 week outpatient trial.
 Recently, the UG1 Laboratory grants at UPenn and VCU have, in collaboration with NIDA,
proposed to screen a medication identified by data-mining, olanzapine, for clinical efficacy
 (Primary Aim: reduction in illicit opioid use) in a two-site (n=24 per site), 8-week observational trial
for buprenorphine-stabilized OUD patients with symptoms of Serious Mental Illness (SMI).
 Secondary Aims feature reduction in other illicit drug use and improvement in sleep; Exploratory
Aims include improvements in MAT adherence, in study retention, and in thought and mood
disorder symptoms. Both the initial demonstration project (cariprazine) and the olanzapine
participants will also receive a battery of phenotypic probes (e.g., for reward/inhibition;
 neurocognition) to capture relapse vulnerability, and likely heterogeneity in medication response.

## Key facts

- **NIH application ID:** 10395761
- **Project number:** 3UG1DA050209-02S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Anna Rose Childress
- **Activity code:** UG1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $165,354
- **Award type:** 3
- **Project period:** 2021-07-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395761

## Citation

> US National Institutes of Health, RePORTER application 10395761, A Clinical Laboratory with Integrated Neuroscience (CLIN) for Early Evaluation of Medications for Substance Use Disorders (3UG1DA050209-02S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10395761. Licensed CC0.

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